Epidemiology of neurodegenerative diseases in sub-Saharan Africa: a systematic review

  • Alain Lekoubou1,

    Affiliated with

    • Justin B Echouffo-Tcheugui2, 3 and

      Affiliated with

      • Andre P Kengne4, 5, 6, 7Email author

        Affiliated with

        BMC Public Health201414:653

        DOI: 10.1186/1471-2458-14-653

        Received: 9 September 2013

        Accepted: 19 May 2014

        Published: 26 June 2014

        Abstract

        Background

        Sub-Saharan African (SSA) countries are experiencing rapid transitions with increased life expectancy. As a result the burden of age-related conditions such as neurodegenerative diseases might be increasing. We conducted a systematic review of published studies on common neurodegenerative diseases, and HIV-related neurocognitive impairment in SSA, in order to identify research gaps and inform prevention and control solutions.

        Methods

        We searched MEDLINE via PubMed, ‘Banque de Données de Santé Publique’ and the database of the ‘Institut d’Epidemiologie Neurologique et de Neurologie Tropicale’ from inception to February 2013 for published original studies from SSA on neurodegenerative diseases and HIV-related neurocognitive impairment. Screening and data extraction were conducted by two investigators. Bibliographies and citations of eligible studies were investigated.

        Results

        In all 144 publications reporting on dementia (n = 49 publications, mainly Alzheimer disease), Parkinsonism (PD, n = 20), HIV-related neurocognitive impairment (n = 47), Huntington disease (HD, n = 19), amyotrophic lateral sclerosis (ALS, n = 15), cerebellar degeneration (n = 4) and Lewy body dementia (n = 1). Of these studies, largely based on prevalent cases from retrospective data on urban populations, half originated from Nigeria and South Africa. The prevalence of dementia (Alzheimer disease) varied between <1% and 10.1% (0.7% and 5.6%) in population-based studies and from <1% to 47.8% in hospital-based studies. Incidence of dementia (Alzheimer disease) ranged from 8.7 to 21.8/1000/year (9.5 to 11.1), and major risk factors were advanced age and female sex. HIV-related neurocognitive impairment’s prevalence (all from hospital-based studies) ranged from <1% to 80%. Population-based prevalence of PD and ALS varied from 10 to 235/100,000, and from 5 to 15/100,000 respectively while that for Huntington disease was 3.5/100,000. Equivalent figures for hospital based studies were the following: PD (0.41 to 7.2%), ALS (0.2 to 8.0/1000), and HD (0.2/100,000 to 46.0/100,000).

        Conclusions

        The body of literature on neurodegenerative disorders in SSA is large with regard to dementia and HIV-related neurocognitive disorders but limited for other neurodegenerative disorders. Shortcomings include few population-based studies, heterogeneous diagnostic criteria and uneven representation of countries on the continent. There are important knowledge gaps that need urgent action, in order to prepare the sub-continent for the anticipated local surge in neurodegenerative diseases.

        Keywords

        Neurodegenerative diseases Parkinsonism Dementia HIV-related cognitive impairment Sub-Saharan Africa

        Background

        Worldwide, populations are increasingly living longer including in developing countries, where the largest number of elderly people is currently found. In sub-Saharan Africa (SSA) (Figure  1), life expectancy at birth has increased by about 20 years between 1950 and 2010 [1]. During this same period, while the proportion of people aged 60 years and above has remained constant at around 5%, the absolute number in this group has increased by about four folds from 9.4 million in 1950 (total population 179.5 million) to 40.3 million in 2010 (total population 831.5 million). In general, population ageing has been described as a more recent phenomenon in SSA, causing figures for this region to be well below the global average [1]. However, projections suggest that the gap in life expectancy between SSA and the world average, which was around 20 years in 2010, will drop to 10 years by 2050. By this time, about 7.6% of the SSA population (estimated total 2.074 billion) will be aged 60 years and above, which in absolute number will translate into four times the 2010 estimates, and correspond approximately to 156.7 million people [2].
        http://static-content.springer.com/image/art%3A10.1186%2F1471-2458-14-653/MediaObjects/12889_2013_6816_Fig1_HTML.jpg
        Figure 1

        Sub-Saharan African countries.

        Population ageing is considered a global public health success, but also brings about new health challenges in the form of chronic diseases including cardiovascular diseases, cancers, as well as neurodegenerative disorders. A characterization and updated picture of the latter conditions in SSA is particularly important in view of a) the ongoing demographic transition and the resulting surge in the prevalence of neurodegenerative diseases in SSA; b) the successful roll-out of antiretroviral therapies in the region and the potential, yet unknown impact of long-term survival with HIV infection and related treatments on the occurrence of neurodegenerative disorders [3]; and c) lastly, the need for reliable data for health service planning. Recently, there have been efforts to summarize existing data for conditions like Parkinson disease (PD) [4, 5] dementia [6, 7] or amyotrophic lateral sclerosis [8], but not for other common neurodegenerative disorders, while there are suggestions of possible African distinctiveness in their occurrence and features [9].

        We systematically reviewed the published literature on common neurodegenerative disorders and HIV-related neurocognitive impairment among sub-Saharan Africans, with the objective of describing their main features as well as clinical and public health implications.

        Methods

        Data sources

        We searched MEDLINE via PubMed, and the French database ‘Banque des Données en Santé Publique’ (BDSP http://​www.​bdsp.​ehesp.​fr) for articles published until February 2013. In addition we searched the database of the ‘Institut d’Epidemiologie Neurologique et de Neurologie Tropicale’ (IENNT). We used a combination of relevant terms to search (in English for PubMed and in French for BDSP and IENNT), which are presented in Additional file 1 (except for IENNT searches for which we used ‘neuroepidemiologie’ and other themes referring to neurodegenerative diseases). Two evaluators (AL and JBE) independently identified articles and sequentially (titles, abstracts, and then full texts) screened them for inclusion (Figure  2). For articles without abstracts or without enough information in the abstract to make a decision, the full text, and where necessary supplemental materials, were reviewed before a decision was made. We supplemented the electronic searches by scanning the references lists of relevant publications, and identifying their citations through the ISI Web of Science, and by hand-searching all issues of the African Journal of Neurological Sciences. Disagreements were solved by consensus or review by a third investigator (APK).
        http://static-content.springer.com/image/art%3A10.1186%2F1471-2458-14-653/MediaObjects/12889_2013_6816_Fig2_HTML.jpg
        Figure 2

        Flow of selection of studies for inclusion.

        Study selection

        We included studies conducted in a country of the SSA region (Figure  1) that reported on the following neurodegenerative diseases among adults: Alzheimer’s disease, fronto-temporal dementia, Lewy body dementia, vascular dementia, cortico-basal degeneration, multi system atrophy, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington disease, cerebellar degeneration, and HIV-related neurocognitive impairment. We made no restriction by study design. We excluded duplicate publications, review articles, studies conducted exclusively in pediatric populations, studies conducted exclusively on migrant populations of African descent living out of the continent. Figure  2 shows the study selection process.

        We provide a rigorous appraisal of the overall data and the epidemiological studies in particular, and make recommendations regarding future approaches to measurement, notwithstanding the challenges involved in such undertakings.

        Data extraction, assessment, and synthesis

        Two reviewers (AL and JBE) independently conducted the data extraction from included studies. We extracted data on study settings, design, population characteristics, measures of disease occurrence (incidence and/or prevalence), and risk factors for the various conditions examined. Given the diversity of neurodegenerative pathologies and the heterogeneity of populations assessed, we did not use a particular framework for the assessment of the quality of studies. However, whenever population-based studies and hospital-based studies had been conducted for a condition, we relied more on the conclusions of population-based studies to address relevant questions, and appropriately reported the results. We conducted a narrative synthesis of the evidence.

        Results

        The study selection process is shown in Figure  2. A total of 4049 citations were identified through MEDLINE, the IENNT database and BDSP searches; 337 abstracts were evaluated in detail and 214 full-text publications reviewed. The final selection included 144 publications reporting on Parkinsonism (20 studies), dementia (49 publications), HIV-related neurocognitive impairment (47 publications), Huntington disease (19 studies), amyotrophic lateral sclerosis (15 studies), cerebellar degeneration (4 studies) and Lewy body dementia (1 study). These studies were published between 1955 and 2012, with about 50% conducted in only two countries: Nigeria and South Africa.

        Parkinson disease, other Lewy body diseases and fronto-temporal dementia

        Twenty studies reported on Parkinsonism (Table  1), including five community-based and sixteen hospital-based. Four were case–control in design and all the others were cross-sectional studies, including reviews of medical records. These studies were conducted in seven countries including Nigeria (ten studies), South Africa (four studies), Tanzania (two studies), Ethiopia, Ghana, Cameroon and Zimbabwe (one studies each). The number of participants with PD ranged from two to 32 and the prevalence from ten to 235/100,000 in community-based studies. The number of participants with Parkinsonism ranged from four to 397, and the prevalence of Parkinsonism varied from 0.41 to 7.2% of neurological admissions/consultations in hospital-based studies. The proportion of men among those with PD ranged from 53 to 100%, and age ranged from 30 to >100 years. Age at the clinical onset of the disease ranged from 17 to 90 years. The clinical types of the disease were largely dominated by Parkinson disease (38 to 100%).
        Table 1

        Overview of studies on Parkinsonism and risk factors in sub-Saharan African countries

        Author, year of publication

        Country

        Setting

        Design/period of study

        Population characteristics

        Diagnosis criteria

        Prevalence

        Profile of parkinsonism patients

        Comments

        Bower [10], 2005

        Ethiopia

        Hospital

        Cross-sectional 2003-2004

        720 patients; 109 (15 · 1%) with movement disorders including 71 men; age 52 y. (13–80)

        Not provided

        72/1,000 of all admissions (PD: 64/1,000)

        N:52; PD:88%

        Review of medical files/outpatient neurology clinic.

        Age (at onset): 57y (30–80)

        Men: 75%

        Akinyemi [11], 2008

        Nigeria

        Hospital

        Case–control 2005-2005

        51 patients (men 37) with PD and 50 controls

        UKPDS Brain Bank criteria

        NA

        N:51; PD: 100%

        22% patients with PD had cognitive dysfunction, with age at PD onset as sole predictor of cognitive dysfunction.

        Age (at onset): 70y (41–80)

        Men:72%

        Cosnett [12], 1988

        South Africa

        Hospital

        Cross-sectional 1979-1985

        2638 patients

        Clinical (Bradykinesia, rigidity, resting tremor and postural instability)

        5.3/1,000

        N:14; PD: 100%

        Retrospective review of medical files/outpatient clinic

        Age: NA

        Blacks: 1.5/1000

        Men: NA

        Indians: 12.6/1000

        Whites: 23.1/1000

        Dotchin [13], 2008

        Tanzania

        Community

        Cross-sectional

        161,071 inhabitants

        UKPDS Brain Bank criteria

        Overall: 40/100,000

        N: 32; PD:100%

        Prevalence is adjusted to UK population. Mean duration 5.1 y

        Men: 64/100,000

        women: 20/100,000

        Age (at onset): 69y (29–90)

        Men: 72%

        Schoenberg [14], 1988

        Nigeria

        Community

        Cross-sectional

        Black population aged 40 + 3412 participants

        Clinical

        Age adjusted: 67/100,000

        N: 2; PD:100%

         

        Age: NA

        Men: NA

        USA

        Community

        Cross-sectional

        Black population aged 40 + 3521 black participants and 5404 white participants.

        Clinical

        Age adjusted:

        N: 12; PD: 100%

         

        Age: NA

        Blacks: 341/100,000

        Men: NA

        Whites: 352/100,000

        Winkler [15], 2010

        Tanzania

        Hospital

        Cross-sectional

        n = 8676 patients admitted (740 with neurological diseases)

        UKPDS Brain Bank criteria

        1/1,000 (all patients)

        N: 8; PD:37%

         

        2003

        11/1,000 (Patients with neurological diseases

        Age: ≥32 y

        Men: 100%

        Community

        Cross-sectional

        1569 people, age 50–110 years

        UKPDS Brain Bank criteria

        235/100,000

        N: 0

        None of the 18 screened-positive was confirmed as having PD. Poisson distribution used to estimate the prevalence.

        2003-2005

        Kengne [16], 2006

        Cameroon

        Hospital

        Cross-sectional

        4041 patients in a neurology clinic145 (3.9%) had neurodegenerative diseases

        Not provided

        488/1,000 of all neurodegenerative diseases; 10.1/1,000 of all neurologic consultation

        N: 41; PD 100%

        4 selected neurodegenerative brain disorders: dementia, PD, ALS, chorea

        1993-2001

        Age: 15-84 y

        Men: 73.2%

        Lombard [17],1978

        Zimbabwe

        Hospital

        Cross-sectional

        Total patients admitted: 83,453 blacks, 34,952 whites

        Not provided

        Blacks: 0.21/1,000

        N: 50 (17 blacks)

        Retrospective review of medical files

        Whites: 2.83/1,000

        Age/men: NA

        Osuntokun [18], 1979

        Nigeria

        Hospital

        Cross-sectional

        217 patients with parkinsonism

        Not provided

        NA

        N: 217; PD 38%

        All patients evaluated by the authors

        1966-1976

        Age: median 51-70 y,

        Men:75%

        Osuntokun [19], 1987

        Nigeria

        Community

        Cross-sectional

        Total participants surveyed: 18,954

        Not provided

        10/100,000

        N. 2; PD 100%

        Screening Questionnaire developed by author

        1985

        Age/men: NA

        Haylett [20], 2012

        South Africa

        Hospital

        Cross-sectional

        229 patients with PD including 163 whites (71%), 45 mixed ancestry (20%), 17 blacks (7%) and 4 Indians (2%)

        UKPDS Brain Bank criteria

        NA

        N: 229; PD 100%

        Mutation in the Parkin gene

        Age (at onset): 54 y (17–80)

        Homozygous or compound heterozygous mutations: 7 patients

        Heterozygous variant: 7

        Men: % NA

        Ekenze [21], 2010

        Nigeria

        Hospital

        Cross-sectional

        8440 admission in the medical ward; 1249 had neurological diseases (men 640)

        Not specified

        21.9/1000 of al neurological admissions

        N: 14

         

        2003-2007

        Age ≥ 70 y (71%)

        Men: 28.6%

        Owolabi [22], 2010

        Nigeria

        Hospital

        Cross-sectional

        6282 admission in the medical ward; 980 had neurological diseases (men 586)

        Clinical: any 3 out of tremor, rigidity, Akinesia/bradikinesia/postural and instability

        4.1/1,000 of all neurological admissions

        N: 4

         

        2005-2007

        Age: (50–68)

        Men; 100%

        Okubadejo [23], 2004

        Nigeria

        Hospital

        Case–control

        33 participants (men 25, mean age 60 y) with PD and 33 match controls

        Any 3 out of tremor, rigidity, Akinesia/bradikinesia/postural and instability

        NA

        N: 33

        Case fatality rate was higher in PD (25% vs. 7.1%), Factors associated with increased mortality: advanced age and disease severity

        Age (at onset): 36-80y

        Men: 75%

        Okubadejo [24], 2005

        Nigeria

        Hospital

        Case–control

        28 participants (men 21, mean age 63 y) with PD and 28 match controls

        Any 2 out of tremor, rigidity, Akinesia/bradikinesia/postural and instability, exclusion of other causes of parkinsonism

        NA

        N: 28; PD 100%

        Autonomic dysfunction rate was higher in PD (61% vs. 6%),

        Age (at onset): 37-76 y

        Men: 76%

        Okubadejo [25], 2010

        Nigeria

        Hospital

        Cross-sectional

        124 participants with Parkinsonism in a neurology clinic

        Any 3 of the following: tremors, rigidity, bradykinesia, and postural or gait abnormality

        15/1,000 of all neurological consultations

        N: 98; PD 79%

        Other causes of parkinsonism n(%): Vascular/drug induced/MSA/LBD: 9(35)/5(19)/4(15)/3(11)

        1996-2006

        Age (at onset): 61y Men: 76.5%

        Keyser [26], 2010

        South Africa

        Hospital

        Cross-sectional

        154 patients with PD including 51 whites (35%), 45 Afrikaners (31%), 29 mixed ancestry (20%), 17 blacks (12%) and 3 Indians (2%).

        UK Parkinson’s Disease UKPDS Brain Bank criteria

        NA

        N: 154; PD 100%

        16 sequence variants of the PINK1gene identified: 1 homozygous mutation (Y258X), 2 heterozygous missense variants (P305A and E476K), and 13 polymorphisms

        Age (at onset): 52 y

        Men: 62%

        Van Der Merwe [27], 2012

        South Africa

        Hospital

        Cross-sectional

        111 patients with early onset PD (men 71) and 286 with late onset PD (men 62%) from a movement disorder clinic

        UKPDS Brain Bank criteria

        NA

        N: 397; PD 100%

        A positive family history was associated with a younger age at onset.

        2007-2011

        Age (at onset): 57 y Men: 248

        Femi [28], 2012

        Nigeria

        Hospital

        Cross-sectional

        1153 participants in 2 Neurologic clinics; 96 (men: 74) had parkinsonism

        presence of at least three of the four cardinal features of tremors, rigidity, bradykinesia, and postural or gait abnormality

        69.4/1,000 of all neurological consultations

        N: 96; PD (83.3%)

         

        2007-2011

        Age: 58 y

        Men: 63.5%

        Cilia [29], 2012

        Ghana

        Hospital

        Case–control

        54 participants with PD and 46 healthy participants

        UKPDS Brain Bank criteria

        NA

        N: 54; PD 100%

        Leucine-rich repeat kinase 2 (LRRK2) gene found in no participants

        Age (at onset): 59 y (30–83)

               

        Men: 61%

         

        NA: Not available; PD: Parkinson’s disease; UK: United Kingdom; USA: United States of America; y: years.

        The most commonly used tool to diagnose PD was the UKPDS Brain bank criteria and population-based (hospital-based) prevalence for the studies that applied those criteria ranged from 40 to 235/100,000 (11 to 69.4/1,000 neurological consultations). In general risk factors were not investigated across studies, although one study found that 38% of patients with Parkinsonism had atherosclerosis and 8% had encephalitis [18].

        We found three cases of Lewy body dementia in a retrospective study in Nigeria, and one case in a retrospective study in Senegal representing respectively 1.2/100,000 of admission over a period of 10 years [30] and 7.5/1000 of participants in a specialized memory clinic [31].

        The prevalence of fronto-temporal dementia has been reported in two hospital-based studies conducted in Neuropsychiatric clinics in Nigeria (prevalence rate: 1.7/100,000 of all admissions) and in Senegal (prevalence rate: 7.5/1000 of all participants evaluated for memory impairment) [30, 31].

        Dementia

        (Table  2) summarizes the 49 publications that reported on dementia. These include 18 hospital-based, 30 community-based publications and one publication from a nursing home. Two were case–control in design, seven were cohort-studies and 40 were cross-sectional, including two autopsy studies. These publications reported on studies conducted in eleven countries: Nigeria (33 publications), Senegal (four publications), Kenya and Tanzania (three publications each), Benin, Central African Republic, Congo republic, (two publications each), South Africa, Cameroon and Zambia (one publication each). In addition, there were seven publications on multicenter studies including African American participants in the USA and participants from African countries [3237]. The overall study size varied from 56 to 2494 in community-based studies and from 23 to 240,294 in hospital-based investigations. The prevalence of dementia ranged from <1% to 10.1% in population-based studies [32, 3457] and from <1% to 47.8% in hospital-based studies [16, 21, 30, 33, 38, 5869].
        Table 2

        Overview of studies on dementia and risk factors in sub-Saharan Africa

        Author, year of publication

        Country/setting

        Design/period of study

        Population characteristics

        Diagnostic criteria

        Incidence

        Prevalence (%)

        Risk factors

        Lambo [58], 1966

        Nigeria

        Retrospective/Cross-sectional, 1954-1963

        328 participants (26% ≥60 y.)

        Not provided

        NA

        Senile dementia*:

        NA

        Hospital

        Overall: 26%, Men: 18.9% Women: 30.5%

        75 cases of dementia (21 men)

        Ben-Arie [39], 1983

        South Africa

        Cross-sectional, 1982

        139 participants aged ≥65 y.

        MMSE/ICD-8 codes

        NA

        Any (severe) dementia 8.6% (3.6%)

        NA

        Community

        Makanjuola [59], 1985

        Nigeria

        Cross-sectional 1979-1982

        51 (5.2% of new consultations); age ≥60 y.

        ICD-9 codes

        NA

        Dementia 11.2%

        NA

        Hospital

        Gureje [60], 1989

        Nigeria

        Cross-sectional, 1984

        1914 patients;

        ICD- 9 codes

        NA

        No case of dementia

        NA

        Community

        Ogunniyi [40], 1992

        Nigeria

        Cross-sectional

        930 participants; age ≥40 y. (293 aged ≥65 y.); No case of dementia

        DSM-III-R criteria

        NA

        No case of dementia

        NA

        Community

        Osuntokun [61], 1994

        Nigeria, hospital Autopsy study

        Cross-sectional 1986- 1987

        111 brains autopsied including 85 patients aged ≤60 y.

        Beta A4 amyloid on brain tissues

        NA

        Heavy/moderate/mild plaque load: 0/6.3/18.9%

        NA

        Osuntokun [41], 1995

        Nigeria, community

        Cross-sectional

        56 subjects (17 with dementia and 12 with AD); age ≥65 y.

        Dementia –CSID

        NA

        APOE ϵ4 allele in dementia/AD/controls 17.6/16.7/20.5%.

        NA

        AD - NINCDS-ADRDA criteria

        Osuntokun [38], 1995

        Nigeria, hospital Autopsy study

        Cross-sectional

        198 brains were autopsied

        senile plaque, neurofibrillary tangle, and amyloid vascular degeneration

        NA

        No evidence of NFT or senile plaque

        NA

        1986- 1987

        Including 45 (23%) ≥65 year

        Hendrie [32], 1995

        Nigeria, community

        Cross-sectional

        2494 participants, age ≥65 y., Dementia -28, AD - 18, VaD - 8.

        Dementia: CSID/DSM-III-R/ICD-10/AD: NINCDS-ADRDA criteria

        NA

        Dementia - Overall/65-74/75-84/≥85 y:

         

        1992-1993

        2.3/0 · 9/2.7/9.6;

        AD - 1.4/0.5/1.7/5.9%

        Indianapolis-USA, community & nursing home

        Cross-sectional

        2212participants, aged ≥65 y. (community) and 106 (nursing home)

        Dementia: CSID/DSM-III-R/ICD-10/AD: NINCDS-ADRDA criteria

        NA

        Dementia Overall/65-74/75-84/≥85 y:

        NA

        1992 - 1993

        8.2/2 · 6/11.4/32.4%

        AD -6.2/1.6/8.0/28.8%

        Ogeng'o [33], 1996

        Tanzania, hospital

        Cross-sectional

        12 Non-demented subjects aged 45–83 y.

        senile plaque, neurofibrillary tangle, and cerebral amyloid angiopathy

        NA

        Amyloid β plaques:17%

        NA

        1996

        Autopsy study

        Neurofibrillary Tangles: 17%; Cerebral Amyloid angiopathy: 17%

        Kenya, hospital

        Cross-sectional Autopsy study

        20 Non-demented subjects aged 45–70 y.

        Senile plaque, neurofibrillary tangle, and cerebral amyloid angiopathy

        NA

        Amyloid β plaques: 15%; Neurofibrillary Tangles: 15%; Cerebral Amyloid angiopathy: 15%

        NA

        USA-Cleveland, Hospital

        Cross-sectional/Autopsy study

        20 Non-demented subjects aged 48–84 y.

        Senile plaque, neurofibrillary tangle, and cerebral amyloid angiopathy

        NA

        Amyloid β plaques: 20%; Neurofibrillary: 15%; Cerebral Amyloid angiopathy: 20%

        NA

        Ogunniyi [42], 1997

        Nigeria, community

        Cross-sectional

        2494 participants aged >65 y screened, 28 with dementia.

        Screening: CSI-D)

        NA

        Any/ AD/ vascular dementia - 1.1/0.7/0.3%

        N A

        1992-1994

        Dementia: DSM-III-R and ICD-10 codes

        AD: NINCDS-ADRDA

        Sayi [62], 1997

        Tanzania, hospital

        Cross-sectional

        24 demented and 286 non-demented participants aged 50–89 y.

        Swahili modified MMSE

        NA

        Prevalence of ϵ4 allele of APOE: Demented - 25%; non demented - 21%

        NA

        Kenya, hospital

        Cross-sectional

        22 demented and 60 non-demented participants aged ≥65 y.

        Swahili modified MMSE

        NA

        Prevalence of ϵ4 allele of APOE: Demented - 42%, non-demented - 27%

        NA

        Baiyewu [63], 1997

        Nigeria, Nursing home

        Cross-sectional

        23 participants (in a nursing home) aged 66–102 y.; 11 women

        DSM-III-R/AGECAT

        NA

        Any dementia (AD) - 47 · 8% (26 · 1%)

        NA

        1994

        Hall [34],1998

        Nigeria, community

        Case–control

        2494 participants; age ≥ 65 y.;

        Screening: CSID

        NA

        18 cases of possible or probable AD1.4%

        age (OR = 1.15; 95%

        423 clinically assessed after screening,

        CI = 1.12-1.18) and female gender (OR = 13.9; 95% CI = 3.85-50.82)

        Dementia: DSM-III-R/ICD-10/AD: NINCDS-ADRDA

        USA–Indianapolis, community

        Case–control

        2212 participants; age ≥ 65 y.;

        Screening: CSID

        NA

        Possible/probable AD 6.2%

        age, family history of dementia, education; rural residence

        Dementia: DSM-III-R/ICD-10/AD: NINCDS-ADRDA

        351 clinically assessed after screening,; 49 (men 17) diagnosed with AD

        Uwakwe [70], 2000

        Nigeria, Hospital

        Cross-sectional

        119 participants; age ≥65 y; 3 had dementia

        Geriatric Mental State and/ICD-10

        NA

        2.8%

        NA

        1995-1996

        Ogunniyi [43], 2000

        Nigeria, community

        Cross-sectional 1992-1994

        2494 participants, age ≥65 y.; 28 with dementia (men: 8) including 18 with AD, 8 with vascular dementia

        Screening: CSID

        NA

        Any dementia 2.3%

        Age (OR: 1.15), female gender (13.9), living with others (OR: 0 · 06)

        Dementia: DSM-III-R/ICD-10

        AD: NINCDS-ADRDA

        AD: 1.4%

        E4 allele in AD (normal subjects) 34.2% (21.8%)

        Indianapolis-USA, community

        Cross-sectional

        2212 participants, age ≥65 year; 65 with dementia including 49 with AD, 10 with vascular dementia

        Screening: CSID

        NA

        Dementia (AD) overall/65-74/75-84/≥85 y – 8.2 (6.2)/2.62 (1.58)/ 11.4 (8.0)/32 · 4% (28.8%);

        Age, rural residence, family history of dementia, education

        Dementia: DSM-III-R/ICD-10

        1992-1994

        AD: NINCDS-ADRDA

        Hendrie [35], 2001

        Nigeria, community

        Prospective cohort Baseline survey in 1992-1993

        2459 participants included after the first visit; 1303 (men 461) completed the follow-up; age ≥65 y.

        Screening: CSID

        Dementia: 13.5/1,000

        NA

        NA

        Dementia: DSM-III-R/ICD-10

        AD: NINCDS-ADRDA

        AD: 11.5/1000

        USA-Indianapolis, community

        Prospective cohort

        2147 African-Americans included after the first visit; 1321 (men 417) completed the follow-up; age ≥65 y.

        Screening: CSID

        Dementia (AD)

        NA

        NA

        Baseline survey in 1992-1993

        Dementia: DSM-III-R/ICD-10/AD: NINCDS-ADRDA

        32.4/1,000 (25.2/1,000)

        Baiyewu [44], 2002

        Nigeria, community

        Prospective cohort baseline survey in 1992-1993

        2487 participants; age ≥65 y.;

        Screening: CSID

        Conversion from CIND to dementia 16 · 1%; From CIND to normal 25 · 3%

        NA

        Sex

        Dementia: DSM-III-R/ICD-10

        423 clinically assessed after screening; 152 diagnosed with CIND; 28 (men 7) with dementia, 87 followed up for 2 years.

        Perkins [36], 2002

        Ibadan-Nigeria community

        Prospective, 1992-1993

        2487 participants; age ≥65 y;

        Screening: CSID

        NA

        1.8%

        Dementia associated with mortality

        Dementia: DSM-III-R/ICD-10

        423clinically assessed after screening

        Indianapolis-USA, Community

        Prospective Baseline survey in 1992-1993

        2212 participants; aged ≥65 y.;

        Screening: CSID

         

        4.9%

        Dementia associated mortality (adjusted RR: 2 · 05)

        342 clinically assessed after screening

        Dementia: DSM-III-R/ICD-10

        Lane [37], 2003

        Nigeria Community

        Prospective 8.7 y follow up Baseline 1992-1993

        968 participants (271 aged ≥75 y.);

        Screening: CSID

        NA

        NA

        ApoEϵ4 alleles not associated with increased mortality

        23with dementia at follow-up

        Dementia: DSM-III-R/ICD-10

        Indianapolis-USA, Community

        Prospective 9.5 y. Baseline 1992-1993

        353 participants (17 4 aged ≥75 y.); 17 with dementia at follow-up

        Screening: CSID

        NA

        NA

        ApoEϵ4 associated with increased mortality for patient under 75 year

        Dementia: DSM-III-R/ICD-10

        Ogunniyi [45], 2005

        Nigeria, Community

        Cross-sectional/1992- 1998

        98 demented subjects; age ≥65 y.

        Screening: CSID

        NA

        AD: 82% of all cases

        NA

        Dementia: DSM-III-R/ICD-10

        VaD: 11.1% of all cases

        Kengne [16], 2006

        Cameroon,

        Cross sectional,

        4041 neurologic consultations

        Not provided

        NA

        0.4% (all neurologic admission), 19% (neurodegenerative diseases)

        NA

        Hospital

        1993-2001

        145 with neurodegenerative diseases

        16 (men 14) with dementia, mean age 67.8 y.

        Gureje [46], 2006

        Nigeria, Community

        Cross-sectional, 2003-2004

        2152 participants at baseline with a respondent rate of 74% (1904 participants). Aged 65 year or older.

        adapted 10-Word Delay Recall Test (10-WDRT)10

        NA

        Overall: 10.1%;

        Female gender, Increasing age, alcohol

        Female: 14.6%

        Men: 7.0%

        Gureje [71], 2006

        Nigeria Community

        Cross-sectional,

        2245 DNA samples, 830 had a diagnosis

        Screening: CSID

        NA

        Any dementia (16.9%

        E4 allele in AD (normal subjects) 26 · 0% (21 · 7%)

        Dementia: DSM-III-R/ICD-10

        AD: 14.8%

        Ogunniyi [72], 2006

        Nigeria, Community

        Case–control

        62 participants with AD (Men 16.1%, mean age 82 y) and 461 non demented (men 33.2%, mean age 77 y)

        Screening: CSID

        NA

         

        Age (OR 1 · 07)

        Dementia: DSM-III-R/ICD-10/AD: NINCDS-ADRDA

        Rural to age (OR 2 · 93) Hypertension (OR 0 · 33)

        Indianapolis-USA, Community

        Case–control

        89 participants with AD (men 30.3%, mean age 83 y), mean age 77 y) and 381 non demented (Men 31.2%, mean age 78 y)

        Screening: CSID

        NA

         

        Age (OR 1.09

        Rural to age (OR 2.08)

        Dementia: DSM-III-R/ICD-10/AD: NINCDS-ADRDA

        Alcohol consumption (OR 0.49)

        Uwakwe [64], 2006

        Nigeria, Community

        Cross-sectional

        30 patients (men 12) with dementia and their caregivers (total 30)

        Not provided

        NA

        N:52;

         

        2003-2005

        AD: not provided

        Men: 12

        Ochayi [47], 2006

        Nigeria, Community

        Cross-sectional 2002

        280 participants; age ≥65 y.;

        CSID

        NA

        Overall dementia: 6.4%

        Female gender,

        Lower body mass index, age, NSAIDS

        65-74 year old: 5.2%

        18 (men 2) with dementia

        ≥85 year 16%.

        Hall [48], 2006

        Nigeria, Community

        Cross-sectional

        1075 participants; age ≥ 70 y. 29 (men 5) with AD,

        NINCDS-ADRDA

        NA

        NA

        Total- or LDL- cholesterol in individuals without the APOE-ϵ4 allele

        Uwakwe [73], 2009

        Nigeria, community

        Cross-sectional

        914 (men 432) participants, age ≥65 y; 87 with ≥2 tests memory tests impaired

        Memory impairment assessed by MMS, CISD and 10 word list immediate and delayed recall

        NA

        9.9%

        NA

        Guerchet [50], 2009

        Benin Community

        Cross-sectional

        502 (men 156) participants, aged ≥65 y; 52 with cognitive impairment

        Screening: CSI-D

        NA

        Cognitive impairment

        Age, current depressive disorder, absence of the APOE ϵ 2

        Overall: 10.4%; men 7.7 women 11.5%

        Dementia: DSM-IV

        AD: NINCDS-ADRDA

         

        Dementia Overall: 2.5%, men 0.6% women 3.4%

        13 (men 1) with dementia

        Toure [67], 2009

        Senegal

        Cross-sectional

        872 participants; age ≥55 y.

        DSM-IV-R

        NA

        Overall 6.6%

        Age, social isolation, history of stroke, epilepsy, family history of dementia, Parkinson’s disease

        Hospital

        2004-2005

        58 cases of dementia

        Napon [68], 2009

        Burkina Fasso

        Cross-sectional

        15815 (2396) out (in) participants; age ≥15 y.; 72 (and 53 inpatients) with dementia; AD: 7; VaD: 19 cases

        DSM-IV

        NA

        outpatients: 0.45% inpatients: 0.22%

        NA

        Hospital

        Guerchet [49], 2010

        Central African Republic Community

        Cross-sectional

        509 interviewed; 496 (men 218) included in final sample, age ≥65 y.

        Screening: CSID

        NA

        Overall: 8.1%, men 2.7%, women 12.2%

        NA

        2008-2009

        Dementia: DSM-IV

        188 with cognitive impairment and 40 (men 6) with dementia (mean age 76 y.); 33 (men 3) with AD and 7 (men 2) with VaD

        AD: NINCDS-ADRDA Hachinski scale,

        Republic of Congo Community

        Cross-sectional

        546 interviewed; 520 (men 198) included in final sample, age ≥65 y.

        148 with cognitive impairment and 35 (men 9) with dementia (mean age 79 y.); 24 (men 7) with AD and 11 (men 3) with VaD

        CSID/ DSM-IV and NINCDS-ADRDA Hachinski scale

         

        Overall: 6.7%, men 4.5%, women 8.1%

        NA

        2008-2009

        Chen [65], 2010

        Kenya

        Cross-sectional

        100 participants; age ≥ 65 y.

        CSI-D using a version in Kikuyu.

        NA

        Apo ϵ4 allele frequency:

        NA

        Hospital

        Demented 31.3%, non-demented 32.2%

        84 controls (men 38) and 16 with dementia participants (men 7)

        Ekenze [21], 2010

        Nigeria

        Cross-sectional

        8440 admissions; 1249 (men 640) with neurological diseases (age range18-83 y.); 38 (men 23) with dementia

        Not specified

        NA

        3%

        NA

        Hospital

        2003-2007

        Siddiqi [69], 2009

        Zambia

        Cross-sectional

        443 inpatients (men 219); median age 39 y., 67 with HIV; 368 outpatients (men 168); median age 39 y., 58 with HIV; 36 with dementia

        Not specified

        NA

        Dementia:

        Dementia in HIV + patients 8 (13.8%) vs. general population 9 (2.9%) (p = 0.002)

        Overall: 4.4%

        Hospital

        2006

        Yusuf [74], 2011

        Nigeria Community

        Cross-sectional

        322 participants (men 128); mean age: 75.5 y

        Screening: CSID/CERAD/SDT

        NA

        Dementia: 2.8%

        Age

        AD: 1.9%

        VaD: 0.6%

        Dementia: DSM-IV and ICD-10

        9 cases of dementia (men 3); mean age: 82.4 y

        LBD: McKhan clinical criteria

        FTD: McKeith clinical criteria

        Gureje [51], 2011

        Nigeria, Community

        Prospective Cohort Baseline 2003-2004

        2,149 participants at baseline

        10-Word Delayed Recall

        21.80/1,000

        NA

        Poor social engagement, rural residence, low economic status, female gender, age.

        Test (cut off of 18)

        1,408 at 39 months follow-up; 85 (among ≥65 y.) developed dementia

        Ogunniyi [52], 2011

        Nigeria Community

        Cohort study

        1559 participants aged > 65 year without dementia a baseline. 136 (men 33) with dementia (mean age 83.1 y.) at follow-up; 255 with MCI

        Dementia: DSM-III-R and ICD-10

        Dementia: 8.72/1,000/year

        NA

        Low BMI

        1992-2007

        MCI: 16.35/1000/year

        Ogunniy [53], 2011

        Nigeria Community

        prospective cohort baseline 1992

        2718 participants interviewed

        Dementia: DSM-III-R and ICD-10

        Dementia/AD/VaD (per 1,000/year) 11.50/9.50/1.10

        NA

        Higher SBP, DBP and PP

        1753 (age ≥65 y.) in the final sample

        120 (men 30) with dementia (mean age 83.8 y.); 99 with AD; 11 with VaD

        Paraïso [56],

        Benin Community

        Cross-sectional

        1,139 (men 523) participants; age ≥65 y.; 42 (men 13) with dementia (mean age 79 · 1 y)

        Screening: CSI-D

        NA

        Dementia Overall 3.7% men 1.1% women: 2.5%

        NA

        2011

        2008

        Dementia: DSM-IV

        32 with AD, 105 with CIND

        AD: NINCDS-ADRDA

         

        AD Overall 2.8%

        VD Overall 0.8%

        VaD: NINCDS-AIREN

        Amoo [30],

        Nigeria

        Cross-sectional

        240,294 participants

        Dementia: ICD-10

        NA

        Dementia: 45/100,000

        NA

        2011

        AD; 25 · 8/100,000

        Hospital

        1998-2007

        VaD: 7 · 4/100,000

        108 (men 51) with dementia (mean age: 70.1); 62 (men 24) with AD; 18 (men 13) with VaD; 4 (men 2) with mixed forms;

        ADNINCDS – ADRDA

        VaD: NINCDS –AIRENS

        LBD: McKeith criteria,

        FTD: Lund and Manchester Criteria

        4 (men 2) with FTD; 3 (men 0) with DLB; 13 (men 2) with unclassified dementia

        Ndiaye [31], 2011

        Senegal

        Cross-sectional

        132 patients seen at a memory clinic (men 41, mean age: 67 y

        Screening: “Test du Senegal”/modified HodKinson test

        NA

        MCI: 14.4%

        NA

        Hospital

        2004-2005

        57 with dementia; 37 with AD, 10 with VaD, 5 with FTD and 1 with LBD.

        Dementia: 43.2%

        AD: 64.7% of all cases of dementia

        MCI: Petersen criteria

        Dementia: DSM-IV

        Coume [75], 2012

        Senegal

        Cross-sectional

        872 (men 546) participants aged >55 y; mean age 67 · 2 y

        Test du Senegal

        NA

        Cognitive impairment 10.8%

        NA

        Hospital

        2004-2005

        94 (men 65) with cognitive impairment (74 aged > =65 y)

        Baiyewu [54]., 2012

        Nigeria

        Cross-sectional/2001 and 2004

        21 (men 4) participants with normal cognition (mean age 82.8 y.)

        Screening: CSID

        NA

        NA

        NA

        Dementia: DSM-III-R/ICD-10

        Community

        53 (men 4) with cognitive impairment (mean age 80.9); 34 (men 6) with dementia (mean age 83.3 y)

        AD: NINCDS-ADRDA

        Toure [66], 2012

        Senegal

        Cross-sectional

        507 participants; age ≥65 y.

        Screening: Aging in Senegal Questionnaire

        NA

        8.9%

        advanced age (Age ≥80 y, OR 4.3, 95% CI 1.4-13), illiteracy, epilepsy, family history of dementia

        45 with dementia

        DSM-IV-R

        Hospital

        2004-2005

        Longdon [57], 2012

        Tanzania

        Cross-sectional

        1198 (men 525) participants; age ≥70 y; 78 with dementia

        Screening: CSI-D

        NA

        6.4%

        Advanced age

        Community

        2010

        DSM-IV-R

        Onwuekwe [76], 2012

        Nigeria

        Cross-sectional

        135 participants (men: 79), aged between 16–76 y

        MMSE (cut off of 17 for MCI)

        NA

        MCI: 5.9%

         

        Hospital

        2004

        8 with MCI

        Guerchet [55], 2012

        Central African Republic, Congo

        Cross-sectional

        509 interviewed; 496 (men 218) included in final sample; age ≥65 y.; 188 with cognitive impairment

        Dementia: DSM-IV-R/AD: NINCDS-ADRDA

        NA

        Dementia: 7.4%

        Hypertension, low BMI, depressive symptoms, change of residence, age (OR 2.59, 95% CI, early death of one parent, female gender

        2008-2009

        Community

        AD: 5.6%

        546 interviewed; 520 (men 198) included in final sample; age ≥65 y.; 148 with cognitive impairment

           

        Overall 75 (men 15) had dementia 18 with vascular dementia

            

        AD: Alzheimer’s disease; APOE: Apolipoprotein E; ICD: International Classification of Disease; BMI: Body Mass Index; CI: confidence Interval; CIND: Cognitive Impairment and No Dementia; CSID: Community Screening Interview for Dementia; DSM-III-R: Diagnostic and Statistical Manual 3rd edition revised; MMSE: Mini Mental State Examination; NA: Not available; NFT: Neurofibrillary tangle; NINCDS/ADRDA: National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; OR: Odd ratio; SCEB: short cognitive evaluation battery; USA: United States of America; VaD: Vascular dementia; y: years.

        The proportion of men among those with dementia was 7.1 to 69.1%. The mean age of participants ranged from 70.1 to 83.8 years. When provided, age at clinical diagnosis of disease ranged from 80.7 to 83.8 years. Alzheimer disease was the most common form of the disease, representing 57.4 to 89.4 % of all cases [3032, 34, 42, 45, 55, 56, 63, 71, 74], followed by vascular dementia 5.7 to 31.0% of cases [30, 31, 45, 56, 74]. Four publications in Nigeria provided incidence data for dementia ranging from 8.7 to 21.8 cases per 1000 per year [35, 5153]. Incidence of Alzheimer disease ranged from 9.5 to 11.5 per 1000 per year [35, 53].

        The most commonly used tool for dementia screening was the Community Screening Interview for Dementia (CSID) questionnaire applied in 20 publications [32, 34, 36, 37, 4143, 4547, 49, 50, 54, 56, 65, 70]. The diagnosis of dementia mainly relied on the DSM-III-R/DSM-IV and ICD-10 classification [30, 32, 3437, 40, 4246, 5254, 63, 70]. The diagnosis of Alzheimer’s disease was based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria [30, 32, 34, 35, 41, 43, 48, 50, 5256, 75]. Population-based studies that used DSM-III/DSM-IV and ICD-10 for dementia reported prevalences ranging from 1.1 to 8.1% [32, 35, 42, 49, 5557, 65, 67, 74] (ref 13, 16, 23, 30, 36–38, 48, 50, 118). Likewise the prevalence of Alzheimer’s disease ranged from 0.7 to 5.6% based on NINCDS/ADRDA criteria [35, 42, 55].

        Risk factors for dementia were reported in 14 publications. The following were associated with an increased risk of dementia: age (twelve publications), female sex (five publications), low body mass index (three publications), anxiety/depression (three publications), hypertension (three publications), social isolation (two publications), lifetime history of alcohol consumption, elevated total- or LDL cholesterol in those without Apo E ϵ4 (one publication), low socio-economic status, history of stroke and family history of dementia (one publication). The following characteristics were inversely associated with dementia: living with others, use of non-steroidal anti-inflammatory drugs and absence of Apo E ϵ2. Some risk factors were more strongly related to the disease. These include age, which increased the risk of dementia by five to 16% across groups [34, 43], but this effect was much higher after the age of 60 years, more than 100% increase risk especially after the age of 75 [46, 50, 51, 55, 66, 67]. Female sex, low level of education (<6 years), rural residence and family history increased the risk of dementia by >100% [34, 43, 46, 55, 56, 66].

        HIV-related neurocognitive impairment

        Fifty-one hospital-based studies (47 publications) reported on HIV-related neurocognitive impairment (Table  3), of which ten were case–control, six cohort and 31 cross-sectional. These studies were conducted in 14 countries including South Africa (14 studies), Uganda (eight studies), Nigeria (six studies), Zambia and Kenya (four studies each), Cameroon and Democratic republic of Congo (three studies each) Ethiopia and Malawi (two studies each), Central African Republic, Botswana, Guinea Bissau, Tanzania and Zimbabwe (one study each). A total of 33 out of the 47 selected publications were published during the last 5 years and only 7 before 2000. The absolute number of participants with HIV-related dementia ranged from 0 to 396, with a prevalence ranging from 0% to 80%.
        Table 3

        Overview of studies on HIV-related dementia and risk factors in sub-Saharan

        Author, year of publication

        Country/setting

        Design/study period

        Population characteristics

        Diagnostic criteria

        Prevalence

        Risk factors

        Comments

        Belec [77], 1989

        Central African republic, Hospital

        Cross-sectional 1987

        93 HIV + participants; age and sex not specified

        Not reported

        HAND: 3 cases (3.2%)

        NA

        No neuro-imaging or neuropathological studies

        Howlet [78], 1989

        Tanzania, hospital

        Cross-sectional 1985-1988

        200 (men 129) HIV + participants; mean age: 32 y

        Decline of memory and other functions

        Dementia complex: 54%

        NA

         

        Turnbull [79], 1991

        South Africa

        Cross-sectional 1982-1983

        27 haemophilic patients with HIV infection

        Battery of neuropsychological tests: Rey complex figure, Babcock story, digit span, WAIS

        HAND: 4 cases (14.8%)

        NA

         

        Perriëns [80], 1992

        Democratic republic of Congo Hospital

        Cross sectional 2008

        104 (men 48) HIV + participants; mean age: 34.3 y.; 92 (men 53) HIV- participants; mean age 44 y 9 (men 5) HIV + with HAND

        WHO operational criteria/American Academy of neurology criteria

        HIV Associated |Dementia Complex. 8.7%

        NA

        No neuro-imaging study

        Maj [81], 1994

        Kenya Hospital

        Cross sectional 1990-1991

        65 (men 49) HIV- participants; mean age: 30 y.; 66 (men 42) asymptomatic HIV + participants; mean age 30.7; 72 (men 48) symptomatic HIV + participants; mean age: 33.2 y

        ICD-10/DSM-IV

        Dementia HIV- 0 Asymptomatic HIV + 0 Symptomatic HIV + 6 (%)

        NA

         

        Democratic republic of Congo Hospital

        85 ( men 48) HIV- participants; mean age: 33.9 y; 52 (men 33) asymptomatic HIV + participants; mean age 32.3 y.; 68 (men 35) symptomatic HIV + participants; mean age: 33.8 y

        ICD-10/DSM-IV

        Dementia HIV- 0 Asymptomatic HIV + 0 Symptomatic HIV + (5.9%)

        NA

         

        Carson [82], 1998

        Kenya

        Cross sectional

        78 (men 52) HIV + participants; mean age: 29.9 y.; 138 (men 114) HIV- participants; mean age 29.8 y.

        Revised WAIS, Trails A and Trails B tests, Digit span, Delayed word and d recognition

        NA

        NA

        No difference in neuropsychiatric test performance between HIV + and HIV-

        Hospital

        1994

        Sebit [83], 1995

        Kenya

        Cross sectional

        191 participants, 72 (men 48) symptomatic HIV + (mean age 33.2 y.), 66 (men 42) asymptomatic HIV + (mean age 30.7) and 65 (men 49) HIV- (mean age 30 y.)

        WHO operational criteria/American Academy of neurology criteria

        Mental disorders:

        NA

        No specific data for HIV associated neurocognitive disorders

        Hospital

        1990-1991

        Symptomatic HIV + 7.1%, Asymptomatic HIV + 4.5%, HIV -0

        Democratic republic of Congo (DRC)/Hospital

        190 participants, 68 (men 35) symptomatic HIV + (mean age 33.8 y.), 52 (men 33) asymptomatic HIV + (mean age 32.3) and 85 (men 48) HIV- (mean age: 33.9 y.)

        WHO operational criteria/American Academy of neurology criteria

        Mental disorders:

        NA

        No specific data for HIV associated neurocognitive disorders

        symptomatic HIV + 5.9%, asymptomatic HIV + 1.9%, HIV– 1.2%

        Sacktor [84], 2006

        Uganda, Hospital

        Prospective

        23 (men 5) HIV + participants on

        MSK HIV dementia scale IHDS

        Baseline: Subclinical dementia 35%

        NA

        All participants had CD4 count ≤200 cells/mL and an IHDS ≤ 10 (suggestive of HAND)

        Cohort study

        2004-2005

        HAART (mean age 32.8 y.)

        Re-assessment at 3 and 6 months.

        Mild dementia 61%

        At 3 (6) months: mild dementia 26% (4%)

        Sacktor [85], 2005

        Uganda, Hospital

        Cross-sectional 2003-2004

        81 HIV+; mean age: 37 y.; 100 HIV- mean age: 31.4 y; 21 had HIV dementia

        IHDS (cut off ≤10),

        HIV dementia: 31%

        NA

         

        MSK HIV dementia scale

        Modi [86], 2007

        South-Africa, Hospital

        Cross-sectional

        506 HIV + (men 203) on HAART; mean age/range: 37 years 193 had HIV associated dementia

        American Academy of Neurology AIDS Task force

        HIV dementia: 38%

        NA

        75% had CD4 below 100 cells/mm3

        2005

        Clifford [87], 2007

        Ethiopia, Hospital

        Case–control

        73 (men 67%) HIV + participants (median age 39 y.);

        IHDS

        NA

        NA

        Quantitative neuropsychiatric tests - no difference between groups

        2004

        87 (men 63%) HIV- participants (median age 38 y.)

        Odiase [88], 2007

        Nigeria, Hospital

        case–control

        96 (men 48) symptomatic HIV + patients (mean age 33.6 y.),

        FePsy computerized neuropsychological test battery

        NA

        NA

        Severity of immune suppression predictive of cognitive decline

        2004

        96 (men 48) asymptomatic HIV + (mean age 31.5 y.); 96 (men 48) HIV- (mean age 32.9 y.)

        Wong [89], 2007

        Uganda, Hospital

        Cross-sectional

        78 (men 28) HIV + participants (mean age 37 y.); 24 (men 6) with dementia; 100 HIV – participants

        MSK HIV dementia scale

        HIV dementia. 31%

        Age, low CD4 count associated HIV dementia

         

        2003-2004

        Robertson [90], 2007

        Uganda, Hospital

        Cross-sectional

        110 (men 34) HIV + participants (WHO Stage 2/3/4, n = 21/69/20); mean age 36.7 y.; 49 on HAART

        MSK HIV dementia scale

        NA

        NA

        Pattern of neuropsychological deficits similar to that in western countries.

        2003-2004

        100 (men 60) HIV– controls (mean age 27.5 y.)

        Salawu [91], 2008

        Nigeria, hospital

        Cross-sectional

        60 HIV + (men 24), asymptomatic, naïve of HAART; mean age 32 y)

        CSID

        56.7%

        No correlation between CD4 count and performance on neuropsychological testing

         

        60 HIV- (men 24); mean age: 30.1 y;

        34 had HIV dementia

        Singh [92], 2008

        South Africa, Hospital

        Cross-sectional

        20 HIV + (men 8) participants; median age 34 y

        IHDS-criteria (cut-off ≤10)

        HAND: 80%

        NA

        CD4 < 200 cells/mm3, older than 18 years and not be delirious.

        2007

        16 had HAND

        Säll [93], 2009

        South Africa, Hospital

        Retrospective

        38 HIV + admitted to the psychiatric ward with psychiatric symptoms; mmean age 32.4 y

        DSM-IV

        Dementia: 32%

        NA

         

        1987-1997

        12 had dementia

        Ganasen [94], 2008

        South Africa, Hospital

        Cross-sectional

        474 (men 123) HIV + patients (328 blacks and 135 coloured); mean age 34 y.

        HIV dementia scale

        HAND: 17.1% (IHDS) and 2.3% (MMSE)

        NA

         

        MMSE

        Njamnshi [95], 2008

        Cameroon, Hospital

        Case–control study 2006

        204 (men 64) HIV + participants (mean age 37.2 y.); 204 (men 64) HIV- participants (mean age 37.1 y.)

        IHDS-criteria (cut-off ≤10)

        HAND:

        NA

         

        HIV+: 21.1%

        HIV-: 2.5%

        Sacktor [96], 2009

        Uganda, Hospital

        Prospective cohort

        102 (men 29) HIV + never treated patients (mean age 34.2 y.) started on Stavudine-based HAART

        IHDS criteria

        Base line: 40% had HIV dementia (33% mild, 7% moderate)

        NA

         

        MSK HIV dementia scale

        2005-2007

        Follow-up 6 months

        25 (men 15) HIV- (mean age 30.3 y.)

        At 3 months: 26%, 23% mild, 3% moderate

        At 6 months: 16% (13% mild, 3% moderate

        Njamnshi [97], 2009

        Cameroon, Hospital

        Cross-sectional

        185 (men 61) HIV + participants (mean age 37 y.); 41 with possible HAND (mean age 37y.)

        IHDS-criteria

        HAND: 22. 2%

        Advanced clinical stage, low CD4 count, and low haemoglobin levels

         

        2006

        Sacktor [98], 2009

        Uganda,

        Cross-sectional

        60 HIV + never treated participants; 22 with dementia

        IHDS criteria

        Overall: 36.7%

        HIV subtype D associated with increased risk of HIV dementia

        All participants had CD4, count ≤200 cells/mL and an IHDS ≤ 10 (suggestive of HAND)

        Hospital

        2005-2007

        MSK HIV dementia scale

        Nakasujja [99], 2010

        Uganda,

        Prospective cohort

        102 HIV + (men 28); mean age: 34.2 y; 70 with cognitive impairment at baseline

        IHDS (cut-off ≤10)

        Base line: 68.6%

        NA

         

        Hospital

        2005-2007

        neuropsychological tests and MSK HIV dementia scale

        At 3 months: 36%

        At 6 months: 30%

        Kinyanda [100], 2011

        Uganda,

        Cross-sectional

        618 HIV + (men 169), 83% <45 y

        IHDS (cut-off ≤ 10)

        64%

          

        396 had cognitive disorders

        Hospital

        2010

        Choi [101], 2011

        Guinea Bissau,

        Case–control

        22 HIV-2 + (men 4)participants mean age for those with CD4 < 350 = 55.1 y, mean age for those with CD4 ≥ 350 = 50.3 y)

        IHDS

        HIV+: 22.7% (CD4 < 350 = 27%, CD4 ≥ 350 = 18%)

        age (β = -0.11)

         

        Hospital

        45 HIV- controls (men 1); mean age51 · 9 y)

        MSK HIV dementia scale

        Control: 11%

        Birbeck [102], 2011

        Zambia,,

        Cross-sectional

        496 HIV + (men 205) participants screened within 1 week of initiating ART; mean age 38.1 y)

        I\HDS (cutt-off ≤ 10)

        42.1% (IHDS)

        NA

        Low IHDS score was associated with poor adherence to HAART

        Hospital

        2006-2007

        MMSE (<=22)

        34.4% (zMMSE)

        IHDS administered to 440 participants.

        185 had dementia

        Joska [103], 2010

        South Africa, Hospital

        Cross-sectional

        536 (men 26.7%) HIV + participants (68% blacks, 28% coloured), mean age 34 y.

        HDS (cutt-off ≤ 10)

        HAND: 23.5%

        Age, education, diagnosed duration, post-traumatic stress disorder

        IDHS not yet available by the time of the study

        Kanmogne [104], 2010

        Cameroon

        Case–control

        43 (men 18) HIV- participants (mean age 33.3 y.); 44 (men 17) HIV + participants (mean age 34.9 y.); 22 with AIDs defining conditions, 34% on HAART

        HIV Neurobehavioral Research Center International neuropsychological test battery

        NA

        NA

         

        Hospital

        2008-2009

        Lawler [105], 2010

        Botswana,

        Cross-sectional

        120 (men 60) HIV + patients (mean age 37.5 y.); 97.5% on HAART;

        IHDS-criteria (cut-off ≤9.5)

        HAND: 38%

        NA

         

        2008

        46 with HIV dementia

        Hospital

        Patel [106], 2010

        Malawi, Hospital

        Cross sectional

        179 (men 63) HIV + participants (mean age 36.7 y.); Stage III/IV 90%; 134 on HAART > 6 months;

        IHDS-criteria (cut-off ≤10)

        HAD

        Female gender, low education

         

        2007

        25 (men 14) with HIV dementia

        Overall: 14%

        Men: 22.2%

        Women: 9.5%

        Siddiqi [69], 2009

        Zambia

        Cross-sectional

        443 (men 219) inpatients (median age 39 y., 67 HIV+); 368 (men 168) outpatients (median age 39 y., 58 HIV+); Overall 36 cases of dementia

        Not specified

        NA

        HIV+: 10.4%

        HIV + patient had a higher frequency of dementia and had dementia at younger age

        Hospital

        HIV-: 3.3%

        Ekenze [21], 2010

        Nigeria, Hospital

        Cross-sectional

        8440 admissions; 1249 (men 640) with neurological diseases (mean age 45 y.); 44 (men 18) with AIDS dementia complex

        Not specified

        AIDS dementia complex: 3.5% of all neurological admission

        NA

         

        2003-2007

        Holguin [107], 2011

        Zambia, Hospital

        Case–control

        57 (men 30) HIV- participants (mean age 28 y.); 83 (men 32) HIV + (mean age 34 y.) including 54 naïve of HAART

        IHDS (cut-off ≤ 10)

        HAND = 22% among HIV + naïve of ARV

        NA

         

        Color Trails Test 1 and

        2008

        2, Grooved pegboard Test, and Time Gait Test

        Joska [108], 2011

        South Africa, Hospital

        Case–control

        94 (men 36) HIV- participants (mean age 25.2 y); 96 (men 20) HIV + (mean age 29.8 y)

        IHDS

        NA

        Education associated with IHDS total score

        Validation study of the IHDS

        2008

        Obiabo [109], 2011

        Nigeria,

        Prospective Cohort study

        69 (men 25) HIV + participants with CD4 < 350 (mean age 36.2 y.); 30 (men 11) HIV- (mean age 36.6 y.)

        CSID and FePsy computerized neuropsychological test battery

        NA

        NA

        HAART improved neuropsychological performances after 12 months of treatment

        Hospital

        Joska [110], 2011

        South Africa Hospital

        Cross-sectional

        170 (men 44) HIV + participants (mean age 29.5 y.)never treated; 43 (men 14) with HIV-dementia; 72 (men 19 with MND

        AAN revised criteria

        Mild neurocognitive disorder: 42.4% HIV dementia: 25.4%

        Education, and male gender independent predictors of HIV-dementia

         

        2008-2009

        Robertson [111], 2011

        Malawi,

        Cross sectional

        133 (men 39) never treated HIV + patients (median age 31 y.)

        Not provided

        MND: 8%

          

        HAD: 0%

        Hospital

        South Africa,

        167 (men 60) never treated HIV + patients (median age 34 y.)

        Not provided

        MND: 4%

          

        HAD: 0%

        Hospital

        Zimbabwe, Hospital

        80 (men 31) never treated HIV + patients (median age 36 y.)

        Not provided

        MND: 14%

        NA

        860 HIV + HAART naïve patients with CD4 count < 300 cells/mL and KI ≥70%

        HAD: 3%

        Robbins [112], 2011

        South Africa,

        Cross-sectional

        65 (men 23) HIV + patients on HAART for ≥6 months (mean age 38.5 y)

        IHDS and Xhosa-validated IHDS

        HIV Associated dementia 80%

        Low CD4 counts, alcohol dependency

         

        Hospital

        2009-2010

        Kwasa [113], 2012

        Kenya,

        Cross sectional

        30 (men 17) HIV + patients (mean age 39 y.)

        Neuropsychological test battery MMSE/IHDS (cut-off ≤10)

        HAD 20%

        NA

         

        Hospital

        6 (men 5)with HAD

        Spies [114], 2012

        South-Africa,

        Case–control

        35 HIV + without childhood trauma; mean age: 31.5 y

        Neuropsychological test battery

        NA

        NA

        Significant HIV effects for the Hopkins Verbal Learning Test (HVLT) learning and delay trials and the Halstead Category Test (HCT)

        Hospital

        48 HIV + with childhood trauma; mean age: 31.7 y

        27 HIV- without childhood trauma; mean: 25y

        20 HIV- with childhood trauma; mean age: 27 · 7 y

        All participants were women.

        Hestad [115], 2012

        Zambia, Hospital

        Case–control

        38 HIV + (men 16); mean age: 28.3 y 42 HIV- (men 18); mean age: 28.9 y

        Neuropsychological tests

        NA

        NA

        HIV + individuals performance lower than that of HIV- on verbal fluency, executive function, speed of information processing, verbal episodic memory and motor function

        Berhe [116], 2012

        Ethiopia,

        Cross-sectional

        347 HIV + (men 176) participants; mean age/range: 34.6 y admitted with neurological disorders

        “cognitive and motor abnormalities, CT/MRI showing brain atrophy and other opportunistic infections ruled out”

        HIV encephalopathy: 0.3%

        NA

         

        Hospital

        Retrospective

        10 had dementia

        2002-2009

        Joska [117], 2012

        South Africa,

        Prospective

        166 HIV + participants assessed at baseline, 108 reassessed at one year (82 received HAART)

        Neuropsychological tests

        NA

        Lower level of education

        Improvement on neuropsychological tests for all participants at one year.

        Average Global deficit score

        Hospital

        Breuer [118], 2012

        South Africa,

        Cross-sectional

        269 HIV + (men 97) participants on HAART for ≥6; months; 34% aged >40 y)

        IHDS (cut-off ≤10.5)

        HAND: 12%

        NA

         

        Hospital

        Hoare [119], 2012

        South Africa

        Cross-sectional

        43 stage III HIV + (24 with at least one ϵ4 ApoE allele, men: 8, Age: 29 y and 19 without the ϵ4 ApoE allele, men: 2, Age: 28 y)

        Neuropsychological test battery

        NA

        Performance on Hodgkin Verbal Learning Tool- Revised was poorer in the group with the ϵ4 genotype.

         

        Participants with the ϵ4 genotype had more white matter injury on MRI.

        Hospital

        Oshinaike [120], 2012

        Nigeria

        Case–control

        208 HIV + (men 71), mean age: 36.8 y

        IHDS (cut off ≤10)

        HAND by MMSE: 2.9%

        Lower CD4 count

         

        Hospital

        2007-2008

        121 HIV – (men: 35), mean age:38.0 y

        MMSE (cut off ≤26)

        AAN revised criteria (any value below 2SD)

        HAND by IHDS: 54.3%

        HAND by AAN: 42.3%

        Royal [121], 2012

        Nigeria, Hospital

        Cross-sectional

        60 (men 23) never treated HIV + participants (mean age 34 y);

        IHDS (cut off ≤10)

        28.8% HIV + individuals scored abnormally

        Low CD4 count, WHO clinical stage of disease

         

        56 (men 34) HIV- (mean age 29 · 4 y.); 32 had dementia

        16.0% HIV- individuals scored abnormally

        3TC: Lamivudine; AIDS: Acquired Immunodeficiency Syndrome; CD4: cluster of differentiation 4; CSID: Community Screening Interview for Dementia; CT: computerized tomography; DSM-III-R: Diagnostic and Statistical Manual 3rd edition revised; DSM-IV: Diagnostic and Statistical Manual 4th edition; dT4: Didanosine; FePsy: The Ion Psyche Program; HAART: Highly Active Anti-Retroviral Treatment; HAD: HIV Associated Dementia; HAND: HIV Associated Neurocognitive Disorders; HDS: HIV Dementia Scale; HIV: Human Immunodeficiency Virus; ICD-III-R: International Classification of Disease; IHDS: International HIV Dementia Scale; MSK: Memorial Sloan Kettering; MMSE: Mini Mental State Examination; MND: Mild Neurocognitive Disorder; NA: Not available; NVP: Nevirapine; WHO: World Health Organization; y, years; ZDV: Zidovudine.

        The diagnostic tools used to identify HIV-related dementia were variable, making comparison between studies less reliable. However, the International HIV Dementia Scale (IHDS) [89, 95, 97, 105, 107110, 112, 113, 120, 121] and the Sloan Memorial Kettering scale [86, 89, 90, 98] were frequently used. Studies that used the IHDS reported a prevalence ranging from 21.1 to 80%. The mean/median age of participants ranged from 31 to 40 years for those with HIV-related dementia, and men represented 25% to 56% of this group. In the nine studies that investigated etiological factors, the identified determinants of HIV-related dementia were: low level of CD4 count (four studies), low level of education, and advanced age (three studies), comorbid psychiatric conditions (two studies each), advance clinical stage (two studies), male sex, HIV-subtype and duration of disease (one study each). The most commonly reported risk factors of HIV associated dementia were the level of CD4 count [89, 97, 112, 120, 121] and the clinical stage of disease [97, 121].

        Amyotrophic lateral sclerosis and cerebellar degeneration

        Fifteen studies (12 retrospective, 2 cross-sectional and 1 case-series) (Table  4) including 13 hospital and two community-based studies on amyotrophic lateral sclerosis (ALS) have been conducted in 9 SSA countries including Nigeria (four studies), Senegal (three studies), Ethiopia (2 studies), Zimbabwe, Kenya, South Africa, Sudan, Cameroon and Ivory coast (one study each). The number of participants with ALS ranged from two to 73. Two community-based studies provided a prevalence of 15/100,000 and 5/100,000 respectively in Nigeria [19] and in Ethiopia [122]. Five hospital-based studies provided prevalence figures: between 0.2 and 8.0/1000 of all neurologic consultation/admission [16, 21, 122126]. The method of ascertainment of ALS was variable across studies, but electromyography was done in four of the fifteen studies included [125129]. The proportion of men among those with ALS was 57.6 to 100%. The age of those with ALS ranged from 12 to 84 years. When provided, the age at the clinical onset of ALS ranged from 12 to 71 years and the time to diagnosis from 3 months to more than 15 years. In general, risk factors for ALS were not investigated across studies.
        Table 4

        Overview of studies on amyotrophic lateral sclerosis risk factors in sub-Sahara Africa

        Author, year of publication

        Country/setting

        Design/year

        Population characteristics

        Diagnostic criteria/tools

        Prevalence

        Risk factors

        Comments

        Wall [130],1972

        Zimbabwe

        Retrospective

        13 (men 10) consecutive patients; age 24–55 y.

        Clinical (no ENMG)

        NA

        NA

        6 participants had sensory changes

        Hospital-based

        1967-1971

        Osuntokun [126], 1974

        Nigeria

        Retrospective

        92 patients with MND ALS 73; PMA 10, SMA 9

        ENMG/Muscle biopsy/

        21/100,000

        NA

        Mean age at onset: 39 y

        Mean duration of disease exceeded 15 y in 8% of participants

        Hospital-based

        1958 -1973

        4 patients with ALS had poliomyelitis in childhood.

        Osuntokun [19], 1987

        Nigeria

        Cross-sectional

        18954 participants (men 9282); 58% <20 y and 11% > 50 y

        Screening questionnaire developed by the authors

        MND: 15/100,000

        NA

         

        Community-based

        1985

        Cosnett [125], 1989

        South Africa Hospital-based

        Retrospective Cases collected during 9.5 y.

        59 blacks (mean age 47.4 y.); 16 whites and 2 coloured (mean age 54 y.) 9 Indians (mean age 54 y)

        Clinical and ENMG in 45%

        Blacks/white & coloured/Indians (per 100,000) 0.88/2 · 7/1.4

        NA

        Mean age of onset: 47 y (blacks) and 54 y (in whites and Indians)

        29% of participants not followed up.

        Ekenze [21], 2010

        Nigeria

        Retrospective

        8440 admissions; 1249 (men 640) with neurological diseases, mean age 45 y.; 10 (men 4) with ALS

        Not specified

        800/100,000

        NA

         

        Hospital-based

        2003-2007

        Abdulla [127], 1997

        Sudan

        Retrospective:

        28 (men 17) patients with MND; 19 (men 14) with ALS

        Clinical and ENMG

        NA

        Family history of MND in 14%

        Mean age of onset: 40 y

        Hospital-based

        1993-1995

        Kengne [16], 2006

        Cameroon

        Retrospective

        4041 neurologic consultations; 145 with neurodegenerative diseases 10 (men 8) with ALS; mean age 50.9 y.

        Not provided

        12% of all neurodegeneration 250/100,000 of all neurologic consultation

         

        4 selected degenerative brain diseases: Dementia, PD, ALS and chorea

        Hospital-based

        1993-2001

        Imam [131], 2004

        Nigeria

        Retrospective

        16 (men 15) participants; age 16-60 y.

        El Escorial diagnostic criteria for ALS, no ENMG

        NA

        NA

         

        Hospital-based

        1980-99

        Adam [129], 1992

        Kenya

        Retrospective

        47(men 35) participants with MND;

        Clinical (ENMG in 1/3 of participants)

        NA

        NA

        Duration of disease: 5 m to 4 y.

        Hospital-based

        1978-88

        Age 13-80 y

        18 had ALS

        Tekle-Haimanot [122], 1990

        Ethiopia

        Cross-sectional

        60820 participants (men 29412), 59% aged < 20 y

        Screening questionnaire and neurological exam

        5/100,000

        NA

        A population survey of neurological diseases

        Community-based

        1986-88

        3 (2 men) had MND

        Harries [132], 1955

        Ethiopia

        Case series

        2(all males) participants

        Clinical (no ENMG)

        NA

        NA

         

        Age 26 and 30 y

        Hospital-based

        1954

        Jacquin-cotton [123], 1970

        Senegal

        Retrospective

        6100 participants with neurological disorders

        Clinical (No ENMG)

        290/100,000

         

        A study of patients with paraplegia in a neurological unit

        Hospital-based

        1960-1969

        18 (16 men) participants with ALS, age 25-70 y

        Piquemal [124], 1982

        Ivory coast

        Retrospective

        4000 participants with neurological disorders

        Clinical (no ENMG)

        750/100,000

        NA

        Duration of disease: 3 m to 5 y.

        Hospital-based

        1971-80

        30 (men 22) participants had ALS, 50% aged <40 y

        Collomb [133], 1968

        Senegal

        Retrospective

        18 (17 men) participants with ALS, age 25-70 y

        Clinical (no ENMG)

        NA

        NA

        Duration of disease: 4 m to 13 y

        Hospital-based

        1960-68

        Sene [128], 2004

        Senegal Hospital-

        Retrospective

        33 (19 men) participants with ALS;

        El Escorial

          

        Definite ALS: 57%,

        Probable: 30%, Possible ALS: 9%

        Suspect ALS: 3% age at onset 14–67 y.

        (ENMG in half of the patients)

         
         

        based

        1999-2000

            

        Duration of disease: 6 m to 5 y.

        ALS: amyotrophic lateral sclerosis; ENMG: Electroneuromyography; MND: Motor Neuron Disease; NA: Not available; PMA: Progressive muscular atrophy; SMA: Spinal Muscular Atrophy; y: years; m: months.

        One retrospective study in Nigeria reported on two cases (a 32 year old male and a 42 year old female) of cerebellar degeneration among 2 · 1 million admissions over a period of 25 year [14]. One study in Rwanda reported on a family of 33 members, with 15 (including eight men, age at onset 12–49 years) having type 2 spino-cerebellar ataxia [134]. A study in Mauritania reported on 12 cases of cerebellar degeneration-based on clinical criteria, including 9 familial cases (including 7 men, aged 3 to 29 years) and 3 apparently sporadic cases (all men, aged 8 to 50 years) [135]. Another clinic-based study of paraplegia in Senegal reported on 7 cases of spino-cerebellar degeneration among 6100 neurological admissions [123].

        Huntington disease

        Nineteen studies (four community-based studies and 15 hospital-based) investigated Huntington disease; including 8 cross-sectional studies (including reviews of medical records), 10 case series (two to 13 patients), and one case report (Table  5). The studies were conducted in nine countries: South Africa (nine studies), Zimbabwe and Tanzania (two studies each), Nigeria, Mauritius Island, Senegal, Sudan, Togo and Burkina Faso (one study each). The diagnostic of Huntington disease was mostly clinical, based on a constellation of probing clinical elements; however genetic testing was carried out in five studies [136140]. The absolute number of participants with Huntington disease ranged from one to 481. Only one community-based study provided a prevalence estimate of 3.5/100,000 in South-Africa [141]. The hospital-based prevalence of Huntington disease when reported ranged from 0.2/100,000 to 46.0/100,000 [138, 142146]. No study reported data on the incidence of Huntington disease. Among those with the disease, males represented 42 to 100%, and age varied from <9 years to 80 years. When provided, the age at the clinical onset of the disease ranged from less than one year to 58 years. In general, antecedent risk factors for Huntington disease were not investigated across studies except for a positive family history reported in 58.3 to 100% of cases.
        Table 5

        Overview of studies on Huntington disease and risk factors in sub-Sahara African countries

        Author, year of publication

        Country

        Setting

        Design/year of the study

        Population characteristics

        Diagnostic tool/criteria

        Prevalence

        Hayden [141], 1977

        South Africa

        Community

        Cross-sectional

        26 cases (men 11); age 12–68 y.

        Clinical

        3.5/100,000

        Samuels [147], 1978

        Zimbabwe

        Community

        Case series

        1 family of HD

        Clinical

        NA

        4 cases (men 2) age 14–26 y.

        Glass [148], 1979

        South Africa

        Community

        Case series

        2 cases of HD (men 1) age 42-52

        Clinical

        NA

        Hayden [142], 1980

        South Africa

        Community/hospital

        Cross-sectional,

        481 cases (m en 241) of whom 153 (m en 69) alive by the time of the study

        Clinical

        Overall: 0.65/100,000, Whites: 2.22/100,000, Mixed ancestry: 2.17/100,000, Blacks: 0 · 01/100,000

        Scrimgeour [149], 1981

        Tanzania

        Community

        Case series

        11 cases, aged 25–80 y.

        Clinical

        NA

        Hayden [143], 1981

        Mauritius

        Hospital

        Cross-sectional

        2166 persons, 6 cases of HD (men 3)

        Not provided

        46/100,000

        Hayden [144], 1981

        South Africa

        Hospital

        Cross-sectional/NR

        17 children (onset before 20 y.) identified during a national survey among of 219 patients

        Not provided

        Overall: 0.6/100,000

        Whites: 0.37/100,000

        Mixed ancestry: 0.89/100,000

        Blacks: No case

        Hayden [150], 1982

        South Africa

        Community/hospital

        Cross-sectional

        157 (men 71) individuals investigated and 328 (women 156, only 3 negro-Africans) deceased individuals with probably HD

        Not specified

        Combined white and black heterozygote frequency = 6 · 7 x 100,000

        Scrimgeour [151], 1982

        Tanzania

        Hospital

        Case series (National registry)

        7 patients with chorea (1 aged 80 y.) and 50 potential patients with chorea in 23 families

        Not specified

        NA

        Mean age at onset: 36 y.

        Aiyesimoju [145], 1984

        Nigeria

        Hospital

        Cross sectional 1957-1982

        2.1 million patients admitted to the hospital.

        Not specified

        HD: 0.2/100,000

        4 cases (men 3) of HD aged 24–50 y at diagnosis.

        Stephany [146], 1984

        Senegal

        Hospital

        Cross sectional

        12370 patients seen in a neurologic clinic; 3 (men 2) with HD; age 31–64 y.

        Family history

        24.2/100,000

        All patients had movement disorders and neuropsychiatric features

        1960-1980

        Joubert [136], 1988

        South Africa

        Community/hospital

        Cross-sectional 1983-1986

        8 cases in hospital setting (n = 6. all men) and at home (n = 2);

        Clinical/genetic testing/screening for Wilson disease

        NA

        Age at onset: 8–47 y.

        Age at diagnosis: 13–50 y.

        Scrimgeour [152], 1992

        Zimbabwe

        Hospital

        Case series1991

        11 cases in a 4 generation of a single family; 2 probable cases

        Clinical

        0.5/100,000

        Scrimgeour [153], 1995

        Sudan

        Hospital

        Case-report

        1 case of HD: A

        Clinical/MRI

        NA

        40 year old black Sudanese man

        Grunitzky [154], 1995

        Togo

        Hospital

        Case series

        A family including 8 patients with HD and 67 at risk across 6 generations; mean age at onset: 33 y.

        Not specified

        NA

        Silber [137], 1998

        South Africa

        Community

        Case series

        5 families of HD including a total of 7 genetically confirmed cases of HD and 10 clinically suspect cases of HD

        Clinical/genetic testing

        NA

        Kabore [138], 2000

        Burkina-Faso

        Hospital

        Case series

        4 cases of HD; age at diagnosis 33–43 y.

        Clinical/genetic testing

        0.04/100,000

        Bardien [139], 2007

        South Africa

        Hospital

        Case series 2001-2005

        A family with HD like 2

        Clinical/genetic testing

        1

        Total 39 family members

        13 had the disease

        Magazi [140], 2008

        South Africa

        Hospital

        Case series

        12 cases (men 6); age 25–52 y.

        Clinical/genetic testing

        NA

        HD; Huntington disease; MRI: magnetic resonance imaging; NA: not applicable; NINCDS-ADRDA, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association; y: year.

        Discussion

        This review represents an unprecedented effort to summarize epidemiological data on neurodegenerative diseases in SSA. However, this being a large diverse multicultural and multiethnic region, it is difficult to reliably quantify and compare the burden of neurodegenerative disorders across countries. Although mostly based on prevalent cases and on retrospective data, from studies that have essentially included urban populations, findings summarized in the current review are very informative.

        The most widely investigated and prevalent neurodegenerative condition appeared to be dementia with most cases being of Alzheimer disease type. Major risk factors of AD include an advanced age (higher after the age of 60), female sex, a low schooling (less than 6 year of education), family background and rural residence. Unlike North America, Australia, Europe, and Japan where several population-based studies have been conducted on dementia, good quality epidemiological studies (prospective, population-based, using standardized criteria) are scanty in SSA, with methodological issues hampering any meaningful comparison with other regions of the world. The reported prevalence in one collaborative good quality study in Nigeria about 20 years ago among those aged >60 years was 2.3%. This was lower than the reported prevalence in developing countries, but within the range of reports from developing countries in Asia and Latin America where reported prevalence range from 1.9 to 3.8% [155]. The anticipated ageing of the population (which is the main driver of dementia figures) in Africa may translate in a higher prevalence and absolute number of people living with dementia as observed in other developing regions. However, caution is needed when interpreting findings from studies conducted in different settings by different investigators. Our overview tends to suggest that the projected increase in the prevalence of dementia in SSA is likely, based on the comparison of findings from three recent studies with those from the study above conducted in Nigeria 20 years ago [5557]. Furthermore, with the large scale implementation of antiretroviral therapy and related improved survival, it is expected that the number of patients with the diagnosis of HIV-related neurocognitive impairment may increase as suggested by the increasing number of related-publications. Such trends will need to be confirmed by large scale prospective observational studies which will also assess the putative accelerating effect of HIV-related neurocognitive impairment on other types of prevalent dementia and neurodegeneration.

        For Parkinsonism, the wide prevalence range observed both in population and hospital-based studies might also be a consequence of differences in methodologies for case ascertainment, diagnostic criteria, or age distributions of the study populations. These heterogeneities in PD prevalence are not unique to SSA as these have also been observed in Europe where prevalence of PD ranged from 66 to 12,500/100,000 [156]. There have been provisional set of minimal scientific criteria for conducting epidemiological studies on PD which, when adopted at a large scale will improve comparison within SSA and between SSA and other regions of the world [156]. Prevalence rates reported in population-based studies in the continent are limited to two studies and cases were ascertained through screening and neurological exam in one study, thus making any comparison with other region difficult. In ALS and Huntington disease, the picture is less clear as the majority of studies were hospital-based, retrospective in nature, with a final diagnosis not always based on pathology or genetics and the risk factors not properly assessed; thus making comparisons and inferences inaccurate. For these two conditions therefore, important gaps remain to be filled, without which the issues of prevention and control will not be efficiently addressed in the African context.

        The comparatively higher number of population-based investigations of dementia relative to other neurodegenerative conditions in SSA, may at least in part be explained by the availability of standardized and widely accepted screening and diagnostic tools/criteria which facilitate epidemiological studies of dementia [157] as compared with other conditions where existing tools have not always been validated in different settings and therefore remain unpopular [158, 159], or which, by the virtue of their low prevalence makes any assessment in the general population difficult and very expensive. There are context-specific challenges to obtaining key epidemiological data on neurodegenerative conditions in SSA including the low level of patient education, the need to accurately translate available screening and diagnostic tools to local languages, limited number of scientists and clinicians in neurosciences, and competing health interest in the setting of limited financial resources [5, 16].

        Needs in terms of epidemiological data

        In order to improve the knowledge base of each of the neurodegenerative conditions addressed in this review, two main types of epidemiological studies appear necessary and feasible in SSA. A population-based prevalence and incidence study including both urban and rural populations, in order to capture the real variability in socio-economic status and possibility in other factors that may exist in the population. Such a study may serve a dual purpose, providing information on disease rate and identification of key risk factors, as it would permit to establish the sequence of events. Given that such an undertaking could be planned beforehand, it offers the possibility of addressing multiple questions and/or diseases at a reduced cost. Inclusion of a large enough but manageable number of participants would be necessary to ensure adequate precision around the estimates generated. As many patients with possible neurodegenerative conditions would be tempted to consult traditional healers rather than accessing health facilities in SSA, special efforts would be required to ensure that these people are captured by such a study. Also, ascertaining cases of neurodegenerative conditions in a population-based sample may be costly and logistically challenging, particularly with regard to the asymptomatic or mildly symptomatic nature of early stages of some of the diseases, and the lack of validated instruments and appropriate expertise.

        A second type of epidemiological study is a multicenter, hospital-based, registry investigation. The latter has several advantages over a single large-scale cohort study. Large numbers of cases could potentially be collected over a relatively short period of time, with the possibility of comparing resources and outcomes within and across countries. However, the major limitations of this approach include the costs associated with the effort and infrastructure for coordination and communication between centers, as well as data capture and ongoing monitoring and quality control. In addition, there are biases inherent to any such hospital-based study, especially given that in SSA there is major access and cost barriers to care, with a sizeable proportion of patients with neurodegenerative conditions who are never seen by health care providers thus limiting the scope of registries. The degree of such selection bias is likely to vary considerably across centers, affecting both case mix and outcomes. The approach would therefore not provide a study population fully representative of incident cases and the natural history of disease and its management.

        For both types of studies, the definition of the pool of people ‘at-risk’ population could be challenging in the SSA context, given the lack of formal census of the population in many countries; thus making reliable estimation of the effect of individual risk factors difficult. Other methodological issues relate to the assessment of the outcome in a reliable fashion in the African context as discussed above. Hence, a combination of the aforementioned study approaches would probably overcome some of their respective limitations and improve the quality of estimates generated.

        The challenges to performing high quality incidence and prevalence studies of neurodegenerative diseases are well known [159]. Cases of most neurodegenerative conditions are difficult to define and ascertain reliably in population-based sample, and there are problems in relating events and the effects of different exposures to defined ‘at-risk’ populations. With the ageing of the population in SSA, the importance of HIV/AIDS, as well as the surge in risk factors such as hypertension and diabetes that have been linked to dementia [157, 160, 161] and possibly to Parkinson diseases [162, 163], the importance of neurodegenerative disorders would considerably increase over time. Indeed, by 2025, the numbers of people aged 60 years and over will more than double in many countries [164]. With this rapid demographic and nutritional transition, neurodegenerative conditions would become an important public health problem in SSA. Critical investments are therefore necessary to improve surveillance and program-relevant research to provide an evidence base for policy development and effective control and prevention of neurodegenerative diseases. Precise identification of risk factors other than ageing would allow proper prevention effort spanning from primordial to secondary and event tertiary prevention, given that most of those conditions are associated with higher levels of disability and increased risk of death. Community-based risk factor control, combined with high risk approaches and realignment of health systems to incorporate the chronic management of neurodegenerative diseases are needed.

        Strengths and limitations of the review

        Our review is the first of its kind on neurodegenerative conditions in SSA. It is more up-to-date and broader than previous attempts to summarize evidence on single diseases in this setting [48]. By systematically assessing all published articles on these conditions, we aimed to draw the attention on the importance of the conditions in the region, and identify the research priorities. A limitation of this review is inherent to the limitations of the individual studies included. We relied on clinic-based studies where necessary in this systematic review; but such studies have limitations, particularly with regard to the generalization of their results data. However, we have tried to convey a clear understanding of the current burden and risk factors of each condition by examining all published papers across a broad range of clinical, biology, public health, and psychosocial literature, incorporating various types of evidence. By the nature of the disease, the age range for participants in studies on ALS and HIV-related neurocognitive impairment extended to the pediatric age for some studies. It is of note that large number of studies are realized in hospital in Africa, often published in local journals or reported in thesis. It the absence of straightforward strategies for capturing this sort of evidence in a systematic way, we did not account for them, which may have lowered the number of results found in some countries. Finally, the many sources of heterogeneity precluded any meaningful assessed of the quality of the included studies.

        Conclusion

        This review summarizes the body of literature on neurodegenerative disorders in SSA, which is large with regard to Dementia and HIV-related neurocognitive disorders but limited for other neurodegenerative disorders. In addition, it emphasizes some of the challenges in conducting good quality, population-based studies on the continent including the lack of standardized criteria for some neurodegenerative disorders, with most studies limited to few regions/countries on the continent. High-quality prospective cohort studies, which would use internationally- validated criteria, wide catchment areas in several geographic regions, and adjust for the projected ageing of the continent population, by compensating for the imprecise nature of the available data, will help map the epidemiology of neurodegenerative diseases in SSA and improve comparisons with the rest of the world.

        Declarations

        Authors’ Affiliations

        (1)
        Department of Neurosciences, Division of Neurology, Medical University of South Carolina
        (2)
        Hubert Department of Global Health, Rollins School of Public Health, Emory University
        (3)
        MedStar Health
        (4)
        Department of Medicine, University of Cape Town
        (5)
        The George Institute for Global Health
        (6)
        Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht
        (7)
        Non-Communicable Diseases Research Unit, South African Medical Research Council

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