Biological sex differences in neurodegenerative diseases in Africa: a scoping review of evidence and research gaps

Abstract

Background

Biological sex is a well-established determinant of risk, progression, and therapeutic response in neurodegenerative diseases (NDs). However, current evidence on sex differences in NDs is from high-income Western populations. This review aims to map and synthesize evidence on biological sex differences in NDs in Africa, and to identify key research gaps.

Methods

This scoping review was conducted in accordance with the Joanna Briggs Institute methodology and reported in accordance with the PRISMA-ScR guidelines. A literature search was conducted on PubMed, African Journals Online, Sabinet Journals, ScienceDirect, and Google Scholar. We included studies conducted in African countries that reported sex disaggregated data or examined biological sex differences in at least one ND. Data were synthesized descriptively.

Results

All included studies reported sex distribution, but most (about 84%) did so only descriptively. Approximately 17% conducted sex-stratified analyses beyond prevalence. Similar to global epidemiological trends, several studies suggested a higher prevalence or odds of dementia and multiple sclerosis among females, while male predominance was observed in Parkinson’s disease and Amyotrophic lateral sclerosis studies. An earlier onset and a higher mutation frequency in LRRK2-G2019S were reported in females with Parkinson’s disease in some studies, while another study reported a higher mortality rate in females with dementia. No study evaluated sex specific biomarker profiles, disease progression, or treatment response.

Conclusions

Evidence on biological sex differences in NDs in Africa remains limited and is largely descriptive. Mechanistic, longitudinal, and biomarker-based investigations are largely absent.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12883-026-05123-w.

Introduction

Neurodegenerative diseases (NDs) are chronic, progressive neurological disorders characterized by a progressive loss of the structure and function in neurons, ultimately resulting in neuronal death and neurological impairment [1]. They include dementia-type diseases such as Alzheimer’s disease (AD), and frontotemporal dementia, Parkinson’s disease (PD) and related disorders, motor neuron diseases such as amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and HIV-associated Neurocognitive Disorders (HAND) [2]. These diseases are typically irreversible and incurable, though symptom-based treatments can help manage symptoms and slow progression. Globally, the burden of NDs is projected to rise, with a growing share expected in low- and middle-income countries, particularly in Africa, where demographic shifts toward older populations are accelerating [3].

Beyond aging, biological sex is a well-established determinant of ND risk and progression. A sizable body of evidence from Europe and North America has demonstrated significant sex differences in disease epidemiology, clinical presentation, biomarker profiles, progression rates, and therapeutic responses [4–13]. For example, AD has been shown to predominantly affect women. About two-thirds of AD patients are women, with women experiencing a faster, more severe cognitive decline, with the APOEε4 allele, a major genetic risk factor for AD, being associated with a greater increase in risk for heterogeneous female carriers than men [5]. Other NDs, such as PD and ALS, tend to affect more men than women, with an early onset in men compared to women [14]. These sex differences have been attributed to a complex interplay of hormonal, genetic, and biological factors, with key drivers including the loss of estrogen’s neuroprotective effects in post-menopausal women, higher microglial activity, and the potential involvement of androgens in PD and ALS [9, 15–18]. Understanding biological sex differences in NDs is critical to advancing precision medicine and personalized therapeutic strategies [19]. Despite the sizable body of evidence in the literature highlighting sex differences in NDs, they have been largely understudied in African populations.

African populations exhibit the highest levels of global human genetic diversity, distinct environmental exposures, and unique sociocultural contexts that may influence disease expression and progression. Furthermore, there is a severe underrepresentation of individuals from African countries in ND research and clinical trials. Consequently, findings from high-income settings may not be directly generalizable to African populations. To date, the extent to which biological sex differences in neurodegenerative diseases have been studied in Africa remains unclear. Mapping this evidence is essential for identifying knowledge gaps, informing context-specific research priorities, and advancing precision neurology in African settings. This scoping review aims to systematically map the existing literature on biological sex and differences in NDs conducted in African populations and to identify critical gaps for future research.

Methodology

Design

This scoping review was conducted in accordance with the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) [20].

Eligibility criteria

Eligibility criteria were defined using the Population–Concept–Context (PCC) framework, which is recommended for scoping reviews.

Inclusion criteria

Population

• Adults (≥ 18 years)

• Studies conducted in African countries

Concept

• Reports sex-disaggregated data and/or

• Performs sex-stratified analysis and/or

• Adjusts for sex in statistical models and/or

• Examines biological sex differences explicitly

This review focused on biological sex differences. We defined sex as the biological attributes of a person, including chromosomes, reproductive anatomy, and hormonal profiles. The included studies reported male–female classifications without evaluating gender-related constructs.

Condition

• Alzheimer’s disease and related dementias

• Parkinson’s disease

• ALS

• Huntington’s disease

• FTD

• HAND

• Multiple sclerosis (MS)

Classical NDs were the primary focus, but we also included multiple sclerosis and HAND. Although MS is primarily autoimmune, and the neurodegeneration in HAND is secondary to HIV infection, both conditions involve chronic progressive neurodegeneration. Both are characterized by significant neurodegenerative changes with chronic neuroaxonal injury, neuroinflammation, and progressive neurocognitive impairment, and were therefore included because of these shared neurodegenerative features with classical NDs.

Study types

• Observational studies (Cohort, Case-control, and Cross-sectional studies)

• Clinical trials

• Registry studies

• Conference abstracts

• Population-based surveys

• Relevant grey literature (including theses and reports)

Conference abstracts and grey literature were considered for inclusion only if they provided sufficient methodological and outcome data that were relevant to the review objectives. Abstracts and grey literature with inadequate details were excluded.

Exclusion criteria

• Studies conducted exclusively outside Africa without disaggregated African data

• Animal or in vitro studies

• Case reports

• Editorials or commentaries without primary data

Search strategy

We conducted a literature search on PubMed, Google Scholar, African Journals Online, Web of Science, Sabinet journals, and Scopus. Databases were searched from inception to January 2026. Grey literature sources, including university repositories and relevant organizational reports, were also searched. Reference lists of included studies were manually screened to identify additional relevant publications.

Search terms

Search strategies combined controlled vocabulary (MeSH terms) and free-text keywords related to neurodegenerative diseases, biological sex, and African geographic identifiers. Search terms included combinations of:

“neurodegenerative disease,” “Alzheimer’s disease,” “dementia,” “Parkinson’s disease,” “amyotrophic lateral sclerosis,” “frontotemporal dementia,” “Huntington’s disease,” “HAND,” “Multiple sclerosis,” AND “sex differences,” “biological sex,” “male,” “female,” “sex-stratified” AND “Africa” or the names of individual African countries alongside their French equivalents.

Boolean operators (“AND,” “OR”) and database-specific search adaptations were used to optimize sensitivity and specificity across databases. Search strategies were adapted appropriately for each database using database-specific indexing terms and syntax. The complete search strategies for all databases are provided in the Supplementary Material.

Study selection

All identified studies were imported into Zotero reference management software, and duplicates were removed. Two reviewers independently screened titles and abstracts for eligibility. Full texts of potentially relevant articles were assessed independently by both reviewers. Discrepancies were resolved through discussion or consultation with a third reviewer. The study selection process was presented using a PRISMA-ScR flow diagram.

Data extraction

A standardized data extraction form was developed and pilot-tested prior to full data extraction. Extracted variables included:

• Author(s) and year

• Country

• Study design

• Sample size

• Disease type

• Sex distribution

• Type of sex analysis performed

• Key findings related to sex differences

• Adjustments for confounders

• Identified limitations

The extraction form was iteratively refined as necessary.

Data synthesis

Descriptive statistics were used to summarize study characteristics, including geographic distribution, disease categories, and study designs. An inductive thematic analysis was conducted to identify patterns in how sex differences were reported and analyzed across studies. Findings were categorized into domains, including epidemiology, genetics, clinical presentation, biomarkers, disease progression, and treatment response. Results are presented narratively and in tabular format. Consistent with scoping review methodology, a formal risk-of-bias assessment was not performed.

Results

The database search yielded 1,110 articles. We removed 297 duplicates and screened 813 titles and abstracts. Ninety-eight (98) full-text articles were assessed for eligibility, from which 44 studies were included. Figure 1 shows the PRISMA-ScR flow diagram of the study.

Fig. 1.

PRISMA-ScR flow chart for the screening process

Characteristics of included studies

We included 44 studies that were conducted across Africa. Most studies were hospital-based cross-sectional studies, followed by cohort studies and systematic reviews. Table 1 summarizes the characteristics of the studies. Sample sizes ranged from 9 participants to over 3 million individuals in a systematic review of MS prevalence. Geographically, studies were concentrated in Nigeria, South Africa, Morocco, Tanzania, and Egypt. There were limited data from Central and West African countries.

Table 1.

Summary of included studies

Study	Participants	Aim	Study design	Sample size	Disease type	Sex-Related Reporting	Domain assessed	Key Findings
Adeloye et al., 2019 [21] Nigeria	Not specified	To synthesize epidemiological evidence on dementia in Nigeria	Systematic review	10,820	AD	Prevalence stratified by sex	Prevalence and risk factors	Females had 2.2 times the risk of developing AD compared to men
Ogunniyi et al., 2006 [22] Nigeria	Community-dwelling elderly African Americans living in Indianapolis and Yoruba people living in Ibadan, Nigeria	To identify the factors associated with increased risk of incident AD in the two communities.	Cross sectional	1255	AD	Sex was included as a covariate in the model	Risk factors for incident AD	Females had 2.93 times the risk of developing AD compared to men
Duodu et al., 2024 [23] Ghana	Adults aged 45 years or older	To estimate sex differences in the prevalence and associated factors of dementia	Cross-sectional study	800	Dementia	Sex stratified analysis	Prevalence and risk factors	Females had a higher risk of dementia
George-Carey et al., 2012 [24] Nigeria, Egypt, Benin, South Africa, Central African Republic, Republic of the Congo	Predominance of older adults	To estimate the prevalence of dementia and dementia subtypes among community-dwelling elderly people in northern Nigeria	Systematic review	Not specified	AD, VaD Other types	Prevalence stratified by sex	Prevalence and risk factors	Females have a higher overall prevalence, especially in older age groups.
Yusuf et al., 2011 [25] Nigeria	Community-dwelling elderly persons	To determine the prevalence of dementia and dementia subtypes among community-dwelling elderly people in northern Nigeria	Cross-sectional descriptive study	9	AD, FTD	Prevalence stratified by sex	Prevalence and risk factors	More females than males have dementia
Longdon et al., 2012 [26] Tanzania	Community-dwelling elderly persons	To estimate the prevalence of dementia in those who are 70 years and older	Cross-sectional	78	Dementia	Prevalence stratified by sex	Prevalence and risk factors	More females than males with dementia, sex ratio of 0.4
Paddick et al., 2015 [27] Tanzania	Community-dwelling Tanzanians	To report the mortality rate for those with dementia, mild cognitive impairment, and no cognitive impairment at 4-year follow-up.	Prospective cohort study	77	AD, VaD	Sex stratified analysis	Mortality rate	More females than males, with a sex ratio of 0.5 Higher mortality rate in women, 63.5% vs. 60%
Paddick et al., 2014 [28] Tanzania	Cohort of dementia cases	To estimate the proportions of AD and VaD in a prevalent cohort of dementia cases in rural Tanzania	Cross-sectional study	78	AD, VaD. Parkinson’s disease, dementia, and Lewy body dementia	Sex stratified analysis	Prevalence	Predominance of females in all subtypes, highest in AD, with a sex ratio of 0.3
Coume et al., 2012 [29] Senegal	People aged 55 and over who were insured	To estimate the prevalence of cognitive impairment in a population of Senegalese elderly people	Cross sectional	90	Dementia	Sex distribution	Risk factors	More females than males with AD
Njamnshi et al., 2016 [30] Cameroon	HIV-infected adults	To investigate the risk factors for HAND	Cross-sectional study	185	HAND	Prevalence stratified by sex. Sex was included as covariates in the model	Prevalence and risk factors	The presence of HAND was not influenced by sex
Patel et al., 2010 [31] Malawi	HIV-infected adults	To study the prevalence of suspected HAD	Cross-sectional study	179	HAD	Sex was included as a covariate in the model	Prevalence and risk factors	Male sex was an independent risk factor of suspected HAD
Choi et al., 2011 [32] Guinea-Bissau	HIV-infected and non-infected adults	To determine the neurologic manifestations of human immunodeficiency virus-2: dementia, myelopathy, and neuropathy	Case-control study	67	HAND	Sex was included as a covariate in the model	Risk factors	The presence of HAND was not influenced by sex
Joska et al., 2010 [33] South Africa	HIV-infected adults	To examine the frequency of HAND and the relationship between clinical and demographic variables	Cross-sectional study	536	HAND	Sex was included as a covariate in the model	Risk factors	No sex differences in HAND
Joska et al., 2011 [34] South Africa	HIV-infected adults	To evaluate HAND and possible risk factors among HIV-infected individuals awaiting HAART	Cross-sectional study	170	HAND	Sex was included as a covariate in the model	Risk factors	Males had 3.989 times the risk of having HAD.
Broh et al., 2018 [35] Ivory Coast	Adults	To describe the epidemiological and clinical profiles of patients with ALS	Cross-sectional study	11	ALS	Prevalence stratified by sex	Epidemiology and clinical characteristics	Males were more affected, with a sex ratio of 2.7
Moustafa et al., 2022 [36] Algeria	Adults	To describe the epidemiological and clinical profiles of patients with ALS	Hospital-based cross-sectional study	11	ALS	Prevalence stratified by sex	Epidemiology and clinical characteristics	Slight predominance of males with a sex ratio of 1.2 Younger mean age of onset in women (50 vs. 52 years)
Imounana et al., 2015 [37] Morocco	Adults	To describe the epidemiological, clinical, and environmental aspects of ALS in the Moroccan population.	Cross-sectional study	60	ALS	Prevalence stratified by sex	Epidemiology and clinical characteristics	Predominance of males with a sex ratio of 1.5 Higher proportion of solvent exposure in males
Floudiotis et al., 2023 South Africa [38]	Cohort of patients of Black African ancestry -	To describe the nature of ALS in a South African cohort of patients of Black African ancestry	Cross-sectional	71	ALS	Sex distribution	Clinical presentation	Males were the most affected, with a sex ratio of 2:1.
Kengne et al., 2006 Cameroon [39]	Adults	To determine the relative prevalence and characteristics of neurodegenerative disorders of the	Cross-sectional	84	ALS, PD, and dementia	Sex distribution	Prevalence and characteristics	Males were the most affected, with a sex ratio of 2.53
Imam and Ogunniyi, 2004 Nigeria [40]	Adults	To describe risk factors and clinical characteristics	Hospital-based cross-sectional	16	ALS	Sex distribution	Risk factors and clinical characteristics	Males were the most affected, with a sex ratio of 15:1
Massi et al., 2018 Senegal [41]	Adult	To determine the environmental and occupational risk factors of ALS	Case-control	23	ALS	Sex distribution	Risk factors	Males were the most affected, with a sex ratio of 1.9
Dotchin et al., 2011 Tanzania [42]	Community-dwelling Tanzanians in a rural community	To document response to treatment, development of side effects, progression of disease, and feasibility and sustainability of supplying medication to patients in rural Tanzania	Prospective cohort study	32	PD	Sex stratified analysis	Response to treatment, development of side effects, and progression of disease	Male predominance with a sex ratio of 2.2 Higher mortality rates in females, although this was not statistically significant
Williams et al., 2018 South Africa, Nigeria, Zambia and Ghana [43]	Not specified	To descriptively summarize all epidemiologic and genetic studies from SSA published up to May 2016, compare the genetic and epidemiologic results from SSA to those from other populations in Africa outside SSA and review the level of care available and accessible to PD patients in SSA	Systematic review of 11 studies	Not specified	PD	Sex distribution	Genetic and epidemiologic characteristics	All studies observed a male predominance, with a male-to-female ratio ranging from 1.2:1 to 4:1.
Gouider-Kouja et al., 2000 Tunisia [44]	Familial PD cases	To determine inheritance patterns and clinical characteristics of familial PD in Tunisia.	Cross-sectional study	Not specified	PD	Sex distribution	Genetic and clinical characteristics	No sex differences.
Barreh et al., 2024 Tunisia [45]	PD patients	To investigate the clinical features, treatments, and complications of PD in Tunisian patients according to their LRRK2-G2019S profile	Longitudinal retrospective study	393	PD	Sex distribution	Genetic and clinical characteristics	Male predominance was, with a sex ratio of 1.09. A significant difference in sex distribution in LRRK2-G2019S status, with females having a higher mutation frequency.
Zoghlami et al., 2025 Tunisia [46]	PD patients	To describe mortality related to Parkinson’s disease (PD) and movement disorders in Tunisia during 2020–2021	Longitudinal retrospective study	96 deaths in 2020 (95 PD, 1 neuroleptic malignant syndrome) and 166 deaths in 2021 (157 PD, 6 neuroleptic malignant syndrome, 1 secondary parkinsonism, 2 unspecified parkinsonism)	PD	Sex distribution	Mortality	Higher mortality rate in males; 57.3% (2020) and 57.8% (2021)
Bouhouche et al., 2017 Morocco [47]	PD patients	To examine the prevalence of G2019S mutation and compare the motor and non-motor phenotype of G2019S carriers to patients with Idiopathic PD	Cross-sectional study	100	PD	Sex included as a covariate	Genetic mutation	Sex was not a predictor of the G2019S mutation
Atadzhanov et al., 2005 Zambia [48]	PD patients	To determine the inheritance patterns of familial PD, compare clinical characteristics of familial with sporadic PD and assess whether there are ethnic differences in clinical manifestations of the disease	Cross-sectional study	27	PD	Sex distribution	Genetic and clinical characteristics	Male predominance in both sporadic and genetic forms
Achbani et al., 2020 Morocco [49]	PD patients	To investigate sex and age differences in the sociodemographic and clinical profile of PD patients	Cross-sectional study	180	PD	Sex-stratified analysis	Sociodemographic and clinical characteristics	Overall predominance of males with sex ratio of 1.85 Predominance of females in the 30–40 years age group, with a sex ratio of 0.7. Earlier disease onset in females Tremor was the most common symptom at onset in females Bradykinesia was less common in females PD was more severe in males
Bouhouche et al., 2015 Morocco [47]	HD patients	To describe the clinical and genetic characteristics of Huntington’s patients of Moroccan origin	Cross-sectional study	21	HD	Sex distribution	Genetic and clinical characteristics	Female predominance with a sex ratio of 0.6
Magazi et al., 2008 South Africa [50]	Patients with genetically-proven HD	To describe a number of black patients with genetically proven HD and to review its occurrence in Africa	Cross-sectional study	12	HD	Sex distribution	Genetic and clinical characteristics	No sex predominance, sex ratio of 1 No sex differences in the type of genetic mutation Females were more cognitively impaired
Hayden et al., 1982 South Africa [51]	Persons who have died or are living with HD	To determine the prevalence of HD in South Africa	Cross-sectional study	481; 153 were alive.	HD	Sex stratified analysis	Prevalence	No sex differences in prevalence
Bocoum et al., 2022 South Africa [52]	Patients with HD phenotype and their relatives	To describe the clinical and genetic aspects of HD in the Malian population.	Cross-sectional study	18	HD	Sex distribution	Prevalence	Slight female predominance, with a sex ratio of 0.8 Patients with the lowest CAG repeat counts had maternal transmission, whereas those with the highest CAG repeat counts had paternal transmission.
Hayden and Beighton, 1982 South Africa [53]	Persons who have died or are living with HD	To examine and conduct family studies on every patient with HD in South Africa	Cross-sectional study	157	HD	Sex stratified analysis	Prevalence	Slight female predominance, and more females had Juvenile HD. The Huntington’s gene was transmitted 3.2 times more commonly by the father than the mother to patients with juvenile HD
Aderinto et al., 2025 Cameroon, Nigeria, South Africa, Senegal, Zimbabwe, Togo, Burkina Faso, The Gambia, [54]	Not specified	To estimate HD prevalence, describe demographic, clinical, and genetic characteristics, and evaluate clinical outcomes in African populations.	Systematic review of 24 studies in SSA	Not specified	HD	Sex stratified analysis	Prevalence	Sex differences in prevalence varied between studies, with some studies reporting slight female predominance, while others reported no sex predominance
Jamal et al., 2021 Kenya [55]	Patients with MS	To describe the demographic and clinical characteristics of patients with MS	Cross-sectional study	99	MS	Sex stratified analysis	Demographic and clinical characteristics	Female predominance with a male-to-female ratio of 1:4
Aderinto et al., 2025 Algeria, Egypt, Kenya, Libya, South Africa, Sudan, and Tunisia [56]	Not specified	To examine available literature on the prevalence, demographic distribution, clinical presentation, and treatment approaches for MS in Africa	Systematic review	3,431,575	MS	Sex stratified analysis	Prevalence, characteristics, and treatment outcome	Consistent female predominance was observed, with female-to-male ratios ranging from 1.4:1 to 4:1.
Bird and Sitoyoshi, 1975 South Africa [57]	Not specified	To compare the epidemiology of multiple sclerosis in South Africa and Japan	Cross-sectional study	53 cases in South Africa	MS	Sex distribution	Prevalence and risk factors	Predominance of females with a sex ratio of 0.6
Lotfi et al., 2024 Morocco [58]	MS patients	To describe the clinical, therapeutic, and epidemiological profiles of MS patients	Cross-sectional study	170	MS	Sex distribution	Clinical, therapeutic, and epidemiological profiles	Predominance of females
Lotfi et al., 2024 Morocco [59]	MS patients	To assess the dimensions of quality of life most affected among patients with MS in Morocco.	Cross-sectional study	157	MS	Sex distribution Sex was included as a covariate	Quality of life	Female predominance Females had the worst quality-of-life scores. Being a female was an independent predictor of having an impaired quality of life
Lotfi et al., 2024 Morocco [60]	MS patients	To measure the prevalence of fatigue and its impact on the physical, cognitive, and psychosocial abilities of individuals with MS.	Cross-sectional study	152	MS	Sex distribution Sex was included as a covariate	Clinical presentation	Female predominance Females had 2.03 times the risk of experiencing pathological fatigue. The cognitive and psychosocial abilities of women were more affected by pathological fatigue
IIham et al., 2024 Morocco [61]	MS patients aged 18 years or above	To identify the sociodemographic and clinical determinants of quality of life in people with MS	Cross-sectional study	200	MS	Sex distribution	Clinical, therapeutic, and epidemiological profiles	Male sex was significantly associated with better scores on both the physical and mental components
Hamdy et al., 2024 Egypt [62]	MS patients aged 18 years or above	To characterize the demographics and disease features of Egyptian patients	Cross-sectional study	1581	MS	Sex distribution	Clinical, therapeutic, and epidemiological profiles	The majority were females with a female-to-male ratio of 2.11:1
Zakaria et al., 2017 Egypt [63]	MS patients aged 18 years or above	To study the characteristics of Egyptian patients with multiple sclerosis in a new registry	Cross-sectional study	950	MS	Sex distribution	Clinical, therapeutic, and epidemiological profiles	Females represented 72% of subjects, with a female: male ratio of 2.57:1

AD Alzheimer’s disease, PD Parkinson’s disease, VaD Vascular Dementia, MS Multiple Sclerosis, FTD Frontotemporal dementia, HAD HIV-associated dementia, HAND HIV-associated Neurocognitive Disorders, HD Huntington’s Disease, ALS Amyotrophic Lateral Sclerosis, SSA Sub-Saharan Africa

Reporting of sex

All included studies reported sex distribution. However, 83.7% reported only descriptively. The remaining few either presented prevalence stratified by sex or included sex as a covariate in regression analyses. Approximately 17% conducted sex-stratified analyses beyond prevalence. No study examined sex-specific biomarker profiles, genotype interactions, long-term progression (except for limited mortality data in dementia and PD cohorts), and treatment response in NDs.

Disease-specific patterns

Dementia

Several studies reported higher prevalence or odds of dementia among females, with two Nigerian studies reporting a 2–3x higher risk in women. Only one study conducted sex-stratified modeling [23]. One study reported a higher mortality rate in women (63.5% vs. 60%), though this was not statistically significant [27].

ALS

A strong male predominance was consistently reported across most cohorts, with a sex ratio of up to 15:1 reported in one study [40]. One study noted an earlier age of onset in women. No sex-specific survival or progression analyses were performed.

Parkinson’s disease

All studies reported a male predominance, and only one study examined progression and mortality by sex, though differences were not statistically significant. One study reported a significant difference in sex distribution in LRRK2-G2019S status, with females having a higher mutation frequency [45]. No sex-specific motor phenotype analysis was done.

Huntington’s disease

Some studies reported a slight female predominance, while others reported no sex differences in prevalence. Sex-linked inheritance patterns were explored in some studies, with one reporting that paternal transmission was more common in juvenile HD, while another reported fewer CAG repeats with maternal transmission [52, 64].

Multiple sclerosis

A consistent female predominance was reported across African MS cohorts, with female: male ratios ranging from 1.4:1 to 4:1 in a systematic review [56]. Three studies from Morocco showed that females had worse quality-of-life scores, higher fatigue burden, and sex as an independent predictor of impaired quality of life [59, 60, 65]. MS studies showed the highest sex-specific reporting beyond prevalence.

HAND / HAD

There were mixed findings: some studies showed no sex effect, while a small number identified male sex as an independent predictor of HAND after multivariable regression.

Discussion

Our findings demonstrate that while sex distributions are reported in African neurodegenerative disease research, analytical investigation of biological sex differences remains limited. Sex was predominantly treated as a descriptive demographic characteristic rather than as a mechanistic or prognostic determinant of ND. Although prevalence patterns in this review are similar to global epidemiological trends (female predominance in dementia and MS, male predominance in ALS and PD), further investigations into sex-specific disease mechanisms were largely absent in African populations. MS was a notable exception, with several studies evaluating sex differences in quality of life and fatigue burden. However, mechanistic exploration still remains limited. ALS and PD studies consistently showed male predominance, yet phenotypic characteristics, treatment responses, survival, and progression differences based on sex were unexplored. Huntington’s disease studies provide preliminary insights into transmission patterns but lack large-scale analyses of genetic-sex interactions.

Comparison with global literature

In high-income countries, sex differences in neurodegeneration beyond prevalence have been extensively studied, including interactions between APOE genotypes and sex in AD, sex-specific patterns of tau and amyloid biomarkers, sex differences in neuroinflammatory profiles, and differential patterns of therapeutic response [66]. This disparity could be due to limited access to state-of-the-art research facilities and biomarker technologies, which enable high-precision, molecular-level, and longitudinal investigations that go beyond binary, categorical comparisons. Improving access to modern research infrastructure, such as advanced imaging and specialized in vitro models, will enable local researchers in Africa to identify sex-specific mechanisms in disease pathology, progression, and therapeutic responses, thereby bridging this critical gap.

Major evidence gaps

The major gaps identified included the lack of sex-specific biomarker studies, limited longitudinal sex-stratified progression data, limited exploration of genetic interactions, and the lack of randomized trials evaluating sex-specific treatment response. Also, the heavy reliance on hospital-based cross-sectional studies precluded assessment of causality.

Implications for future sex-informed neurodegenerative research in Africa

Knowledge of sex differences in neurodegenerative diseases is absolutely critical to advancing precision medicine on the African continent. The highly diverse and extensive genomic landscape of the African population may substantially influence sex differences in neurodegenerative diseases and, therefore, presents a unique opportunity to investigate and describe such differences that may differ from those observed in Western cohorts. Descriptive studies, although useful, may not capture these differences adequately. Future studies in neurodegenerative diseases in Africa should move beyond descriptive sex reporting and include genomic sequencing, biomarker profiling, neuroimaging, and inflammatory markers within sex-informed analytical frameworks. The establishment of longitudinal cohorts with sex-stratified analyses is essential to understand disease progression, mortality, and therapeutic response across diverse African populations. Additionally, environmental and sociocultural exposures, such as differences in educational access, occupational exposures, healthcare utilization, vascular risk factors, nutrition, and caregiving roles, may modify ND risk and outcomes differently in males and females. Because these factors differ from those in Western populations, where most existing evidence on sex differences in NDs originates, future studies should assess how these factors may interact with biological sex to influence disease expression in African settings.

Furthermore, the sex differences identified in the study highlight the importance of incorporating sex-informed recruitment strategies and adequately powered subgroup analyses in future clinical trials and biomarker studies conducted in Africa. Sex-stratified analyses should become a standard practice. This will be essential for advancing precision neurology, ensuring equitable representation of males and females in African neurodegenerative research.

Conclusion

Sex differences in NDs are well established in Western populations but remain underexplored in Africa. While the observed sex distribution patterns appear broadly consistent with global epidemiological trends, mechanistic investigations, biomarker profiling, and longitudinal sex-based investigations are largely absent. Addressing this gap is essential for advancing precision neurology and ensuring adequate design of future clinical trials.

Strengths and limitations

This review provides the first mapping of evidence on biological sex differences in neurodegenerative diseases in Africa. However, several limitations should be acknowledged. Most of the included studies were hospital-based, cross-sectional, and had small sample sizes. These limit the generalizability of the findings and preclude causal inference. Consequently, the observed sex distribution patterns should not be interpreted as evidence of underlying biological mechanisms or causal associations. Also, geographic representation was uneven, with most included studies conducted in a few countries, particularly Nigeria, South Africa, Morocco, and Egypt. Consequently, the findings may not be truly representative of the African continent. Additionally, the rarity and underdiagnosis of certain neurodegenerative diseases, such as amyotrophic lateral sclerosis and Huntington’s disease, might have contributed to the limited number of available studies on these conditions. Most studies reported sex descriptively rather than through inferential or mechanistic analyses, limiting interpretation of observed differences. Furthermore, none of the included studies assessed gender-related constructs; the findings of this review primarily reflect biological sex differences rather than gender-based determinants of neurodegeneration.

Authors' contributions

All authors were involved in the conceptualization, data curation, formal analysis, methodology, and manuscript preparation. MNN wrote the first draft. All authors read and approved the final manuscript.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

All data generated or analysed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

This systematic review used secondary data from publicly accessible documents as evidence. No primary human data were included in this study. All the authors of the publications used in the review have been acknowledged.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.