Lactoferrin has been proposed as a minimally invasive biomarker for Alzheimer's disease (AD), but its relationship with established AD pathology remains uncertain. We analyzed paired cerebrospinal fluid (CSF) and plasma SOMAscan proteomic profiles from 1,367 participants in the ACE Alzheimer Center Barcelona cohort, focusing on two lactoferrin-targeting SOMAmers, Seq.14755.4 (LTF1) and Seq.2780.35 (LTF2). LTF1 and LTF2 showed distinct distributions and weak concordance across fluids, indicating that they should not be treated as interchangeable lactoferrin measures. In CSF, LTF2 was associated with lower Aβ42 and AD biomarker-defined status, whereas LTF1 showed subgroup-dependent associations with tau markers that were partly influenced by major CSF proteomic axes and reference-gene adjustment. Neither CSF nor plasma LTF signals predicted conversion from mild cognitive impairment to dementia. GNPC analyses supported the non-interchangeability and compartment specificity of LTF signals and identified a reproducible plasma LTF2-centered network enriched for innate immune and granule biology. These findings suggest that lactoferrin-related signals are assay-, compartment-, and network-context dependent rather than standalone AD biomarkers.

White matter hyperintensities (WMH) are frequently observed on MRI in aging and Alzheimer’s disease (AD), yet their microstructural pathology remains poorly characterized. Conventional MRI sequences provide limited information to describe the tissue abnormalities underlying WMH, while histopathology—the gold standard—can only be applied postmortem. Quantitative MRI (qMRI) offers promising non-invasive alternatives to postmortem histopathology, but lacks histological validation of these metrics in AD. In this study, we examined the relationship between MRI metrics and histopathology in postmortem brain scans from eight donors with AD from the South Texas Alzheimer’s Disease Research Center. Regions of interest are delineated by aligning MRI-identified WMH in the brain donor scans with postmortem histological sections. Histopathological features, including myelin integrity, tissue vacuolation, and gliosis, are quantified within these regions using machine learning. We report the correlations between these histopathological measures and two qMRI metrics: T2 and absolute myelin water signal (aMWS) maps, as well as conventional T1w/T2w MRI. The results derived from aMWS and T2 mapping indicate a strong association between WMH, myelin loss, and increased tissue vacuolation. Bland-Altman analyses indicated that T2 mapping showed more consistent agreement with histopathology, whereas the derived aMWS demonstrated signs of systematic bias. T1w/T2w values exhibited weaker associations with histological alterations. Additionally, we observed distinct patterns of gliosis in periventricular and subcortical WMH. Our study presents one of the first histopathological validations of qMRI in AD, confirming that aMWS and T2 mapping are robust, non-invasive biomarkers that offer promising ways to monitor white matter pathology in neurodegenerative disorders. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the South Texas Alzheimers and Neural Degeneration (STAND) Training grant T32 AG082661. This study was supported in part by the National Institutes of Health (NIH) grant P30AG066546 (South Texas Alzheimers Disease Research Center) and grant numbers 5R01HL127659, 1U24AG074855, 5R01AG080821, 1R01AG085571, 5R01AG083865, and the William and Ella Owens Medical Research Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The University of Texas Health Science Center at San Antonio IRB gave full ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The corresponding author can be contacted to discuss data sharing.

Alzheimer's disease (AD) is known as a progressive neurodegenerative disorder. Evidence suggest that Apolipoprotein E ( APOE ) plays a significant role with AD, but only limited work has examined APOE relationships with vascular pathology lesions in the brain. The objective here is to investigate the association between APOE genotypes and vascular pathology lesions using the National Alzheimer's Coordinating Center (NACC) dataset and to further explore absent TDP-43 proteinopathy vs. any TDP-43 proteinopathy. We used NACC data to evaluate the relationship between APOE genotype and vascular pathology lesions: arteriolosclerosis, atherosclerosis, large arterial infarcts, lacunes, hippocampal sclerosis of aging, and hemorrhages and microbleeds. Participants were classified by APOE genotype into APOE ɛ4 carriers (ɛ24, ɛ34, ɛ44), APOE ɛ3 homozygotes (ɛ33), and APOE ɛ2 carriers (ɛ22, ɛ23). Logistic regression models adjusting for age, sex, self-reported ancestry, and education were used. We also assessed effect modification by TDP-43 proteinopathy in the association between APOE genotype and each of the vascular lesions. Statistical significance was set at α=0.05. This study consisted of 7117 participants (mean age 79.1 ± 11.6 years, 47.6% female). Compared to participants with ε3 homozygotes, those carrying at least one APOE ε4 allele have higher odds of Arteriolosclerosis (OR [95% CI], p: 1.19[1.09,1.31],<0.001) and hippocampal sclerosis of aging (1.28[1.07,1.53],0.006) while participants with APOE ɛ2 carriers had an increased odds of large arterial infarcts (1.71[1.15, 2.55],0.009). We observed significant effect modification by TDP-43 proteinopathy in the association between APOE genotype and arteriolosclerosis ( p  = 0.037) and hippocampal sclerosis ( p  = 0.044). Among those with absent TDP-43 proteinopathy, APOE ɛ4 carriers showed increased odds of arteriolosclerosis (1.37[1.12,1.68],0.002) as compared to ε3 homozygotes, but not among those with any TDP-43 proteinopathy present, and none of the other associations were statistically significant. Our findings suggest that carrying at least one APOE ɛ4 allele increases the risk of arteriolosclerosis and hippocampal sclerosis, while the presence of at least one APOE ɛ2 increased the risk of large arterial infarcts. TDP-43 proteinopathy modifies these effects, with APOE ε4 showing stronger vascular and neurodegenerative associations in those with absent TDP-43 proteinopathy but not in those with TDP-43 proteinopathy.

Background Vitamin D3 is essential for calcium metabolism and exerts pleiotropic effects, including neuroprotective activities in cognition. Its insufficiency has been linked to dementia, Alzheimer's disease, and cognitive impairments. The association between vitamin D3 and particular cognitive functions, including memory recall and word intrusion, remains imprecise, particularly among diverse ethnic and socioeconomic groups. Objective To examine the relationship between vitamin D3 levels with memory recall and word intrusion in individuals aged 60 and above, emphasizing demographic differences. Methods Data was collected from 2759 individuals in the NHANES 2011-2014 surveys. Cognitive performance was evaluated with the CERAD Word Learning, Animal Fluency, and Digit Symbol Substitution assessments. Factor analysis was employed to identify two cognitive domains: F1 'Memory Recall' and F2 'Word Intrusion'. Linear and quantile regression models, controlled for demographic variables, were performed to assess the association between vitamin D3 levels and cognitive domains. Bootstrap techniques were used for standard error estimation, and nonparametric regression was applied to identify non-linear correlations. Results Vitamin D3 levels positively correlated in linear models and quantile regression with F1 'Memory Recall' at diminished cognitive function levels. F2 was not associated with vitamin D3. Socioeconomic factors influenced these correlations, revealing inequalities among ethnic and income groups. Conclusions Elevated vitamin D3 levels correlate with improved memory recall, especially in individuals with lower cognitive percentiles. These findings suggest the potential of vitamin D3 to alleviate cognitive decline, including Alzheimer's disease, highlighting the need for focused interventions, particularly in underrepresented demographic groups.

Mesial temporal lobe epilepsy (MTLE) seizures are known to alter neural architecture, yet imaging studies report conflicting findings of their effects on the brain. This study aimed to identify consistent regions exhibiting structural or functional changes in MTLE and compare the regional distributions of pathology detected by different neuroimaging modalities. To that end, thirty-six coordinate-based meta-analyses were performed by applying Alteration Likelihood Estimation to voxel-based morphometry (VBM) and voxel-based physiology (VBP) studies. The meta-analyses revealed convergent MTLE pathology in the epileptogenic hippocampus, bilateral thalamus (medial dorsal nucleus and pulvinar), and striatum (caudate and putamen); significant findings were partially colocalized between VBM-atrophy and VBP analyses, with VBP effects driven primarily by reports of cerebral hypometabolism. Subgroup meta-analyses of blood-oxygen-level-dependent (BOLD) signal-derived metrics revealed additional regions of functional disturbance but were underpowered, requiring further investigation to establish their potential for revealing novel aspects of MTLE pathophysiology via functional magnetic resonance imaging (fMRI). These findings support the current understanding of MTLE as a network-based pathology with progressive neurodegeneration in the hippocampus and connected regions. This study also highlights promising neuroimaging targets for investigating disease-related alterations and recommends incorporating these regions into functional network models of MTLE. Finally, the present work encourages further exploration of BOLD-derived metrics and specifically urges the epilepsy imaging research community to report amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) measures for resting-state fMRI studies in standard space coordinates, to advance neuroimaging approaches for improving diagnosis, prognosis, and treatment strategies in MTLE.

The APOE genotype, particularly APOE -ε4, increases AD risk and influences neuropathology. However, its role in disease progression remains complex, varying with individual factors like age and sex, requiring further investigation. Our objective is to assess the relationship between APOE genotype and neuropathological outcomes and explore modifying effect of TDP-43 proteinopathy. This study used the NACC dataset with 7,117 participants (mean age 79 ± 11.6 years), 47.6% female, 94.6% White, and 30.7% post-master educated. Participants were classified by APOE -ε2 carriers (ε 22 or ε 32) , ε3 homozygotes (ε 33) , and APOE -ε4 carriers (ε 24 , ε 43 or ε 44) . Neuropathological outcomes including Thal Phase, Braak Stage, neuritic plaques, diffuse plaques, and cerebral amyloid angiopathy, were examined. Logistic regression models adjusted for age, sex, self-reported ancestry, and education were used. Additionally, to assess the modifying effect of TDP-43 proteinopathy interaction analyses were performed. Statistical significance was set at α=0.05. Compared to ε3 homozygotes, APOE -ε4 carriers had significantly higher odds of Thal Phase (OR[95%CI], p: 4.70[4.09,5.41],<0.001), Braak Stage (3.78[3.42,4.18],<0.001), neuritic plaques (3.48[3.17,3.83],<0.001), diffuse plaques (3.46[3.12,3.85],<0.001) and Cerebral amyloid angiopathy (3.49[3.18,3.84],<0.001). APOE -ɛ2 carriers showed reduced odds of Thal Phase (0.51[0.42,0.63], <0.001), Braak Stage (0.56 [0.48, 0.66], <0.001), neuritic plaques (0.48 [0.41, 0.56], <0.001), diffuse plaques (0.49 [0.42, 0.57], <0.001). We did not observe any other statistically significant associations. We observed a statistically significant interaction by TDP-43 proteinopathy in the association between APOE and neuritic plaques ( p  = 0.028) but not with other pathologies. The effect of APOE -ε4 was reduced in individuals with any TDP-43 presence (3.68[2.89, 4.69], <0.001) compared to those with absence of TDP-43 (4.17[3.36, 5.17], <0.001). Interestingly, the protective effect of APOE -ε2 was enhanced in individuals with any TDP-43 presence (0.28[0.18, 0.45], <0.001) compared to those with absence of TDP-43 (0.63[0.45, 0.87], 0.006). These findings suggest that TDP-43 proteinopathy modifies the genetic risk associated with APOE , attenuating the impact of APOE -ε4 while amplifying the protective role of APOE -ε2. APOE -ɛ2 carriers appear to have a protective effect. The presence of TDP-43 proteinopathy may further modify these associations. Future studies should explore the impact of additional genetic and environmental factors on AD neuropathology burden.

Background:Pathological changes in Alzheimer's disease (AD) begin years before the onset of clinical symptoms. Developing cost-effective and minimally invasive biomarkers for preclinical diagnosis remains a critical goal in the field. Lactoferrin, an iron-binding glycoprotein, has emerged as a promising candidate due to its multifunctional roles reported in previous studies. However, whether lactoferrin levels in biofluids are associated with established AD biomarkers, and whether it can serve as a reliable diagnostic indicator, remains controversial. Methods:We analyzed SOMAscan proteomic data from 1,367 paired plasma and cerebrospinal fluid (CSF) samples from the ACE Alzheimer's Center Barcelona cohort to evaluate lactoferrin levels. Associations between two lactoferrin-targeting SOMAmers and classical AD biomarkers, including total tau (t-tau), phosphorylated tau (p-tau181), and amyloid-beta 42 (Aβ42), were assessed. The age, sex, proteomic principal components were considered as covariates for sensitive analysis. The prognostic value of lactoferrin in predicting dementia progression was further evaluated using survival analysis. Findings:Among the two lactoferrin-targeting SOMAmers, Seq.2780.35 (LTF2) showed a weak and exclusive association with CSF Aβ42 and syndromic status, whereas Seq.14755.4 (LTF1) was weakly associated with CSF p-tau and t-tau AD biomarker levels displayed expression-dependent stratification consistent with a ventricular-volume-related dilution effect rather than disease. Furthermore, lactoferrin levels were not significantly associated with the progression from mild cognitive impairment (MCI) to dementia. Interpretation:Isoform-specific lactoferrin expression changes in cerebrospinal fluid (CSF), but not plasma, appears to have biological relevance and diagnostic biomarker potential for AD.

Africa, the world's second-largest continent is home to 1.5 billion people, accounting for nearly 20% of the global population, (60% under age 25). By 2050, Africa's population will be 2.5 billion, and by 2035, more young Africans will be entering the workforce each year than in the rest of the world combined. Africa also hosts a rich social, cultural, and geopolitical diversity across its 5 geopolitical zones covering 54 countries. It is the most genetically, culturally, and linguistically diverse region on the planet. However, Africa's contribution to the global economy could be more significant if it urgently embraces the brain economy and leads in the development of new methodologies and approaches which can be exported around the world. In this paper, we explain our strategy to advance the Yaoundé Declaration for the Brain Economy, Brain Health, and Brain Capital. The Declaration has been endorsed by Cameroon's President, His Excellency Paul Biya, and demonstrates African leadership in global brain and society innovations, laying out a roadmap for how Africa can outcompete other economies by deftly deploying brain science-inspired policies and investments. We outline a new economic approach for African jobs, economic growth, sustainability, resilience, health, and well-being. The brain economy offers a broader framework than the current sustainable development goals (SDG) agenda. The Yaoundé Declaration is trans-disciplinary and cross-cutting across sectors: 32 sitting members of government from different sectors having co-authored this paper. It aligns with many aspects of the United Nations Pact for the Future and can accelerate the SDG.

Background: The hippocampus plays a crucial role in memory and is one of the first structures affected by Alzheimer's disease. Postmortem MRI offers a way to quantify the alterations by measuring the atrophy of the inner structures of the hippocampus. Unfortunately, the manual segmentation of hippocampal subregions required to carry out these measures is very time-consuming. New Method: In this study, we explore the use of fully automated methods relying on state-of-the-art Deep Learning approaches to produce these annotations. More specifically, we propose a new segmentation framework made of a set of encoder-decoder blocks embedding self-attention mechanisms and atrous spatial pyramidal pooling to produce better maps of the hippocampus and identify four hippocampal regions: the dentate gyrus, the hippocampal head, the hippocampal body, and the hippocampal tail. Results: Trained using slices extracted from 15 postmortem T1-weighted, T2-weighted, and susceptibility- weighted MRI scans, our new approach produces hippocampus parcellations that are better aligned with the manually delineated parcellations provided by neuroradiologists. Comparison with Existing Methods: Four standard deep learning segmentation architectures: UNet, Double UNet, Attention UNet, and Multi-resolution UNet have been utilized for the qualitative and quantitative comparison of the proposed hippocampal region segmentation model. Conclusions: Postmortem MRI serves as a highly valuable neuroimaging technique for examining the effects of neurodegenerative diseases on the intricate structures within the hippocampus. This study opens the way to large sample-size postmortem studies of the hippocampal substructures.

Observational studies have reported cognitive domain alterations in individuals with Type 2 diabetes mellitus (T2D), affecting cognitive domains of information-processing speed, memory, attention, and executive function. Epidemiological observational studies have shown an association between higher blood pressure [HBP], low processing speed, short-term memory and learning, and delayed recall. Within the US Hispanic/Latino population, specifically Mexican Americans, cognition remains insufficiently studied. This preliminary analysis aims to discern the impact of T2D and hypertension on cognition, employing propensity score matching to mitigate confounders. A dataset with 650 participants without dementia (mean age 50 ± 12.6 years, BMI 29.1 ± 6.6, 63% females) from the Mexican American Family Study Cohort from low economic strata was analyzed. The effects of T2D and HBP were evaluated using propensity score matching, specifically employing nearest-neighbor matching under a logistic model. Coefficients (95% confidence intervals) and p-values were reported. Among the participants, 9% had T2D, 6% had HBP, and 2% had both conditions. Adjusting for sex, age, and BMI, the presence of T2D impacted face memory delay [b = 1.3 (0.1, 2.5) p = 0.032] and Continuous Performance Test (CPT) hits [b = 45.9 (24.7, 67.1) p<0.001]. Hypertension influenced California Verbal Learning Test (CVLT) learning [b = -11.1 (-15.1, -7.4) p<0.001], CVLT recognition [b = -3.2 (-6.1, -0.3) p = 0.03], and CPT hits [b = -31.1 (-64.4, 2.3) p = 0.068)—Figure 1 CVLT score on T2D and HBP status. This preliminary study underscores the heightened risk of hypertension and T2D impacting cognitive function among Mexican Americans. Variations in cognitive measurements based on T2D or hypertension were observed, emphasizing the need for specific cognitive screening tools tailored to the prevalence of chronic conditions in this susceptible population.

The quality of life (QoL) perception has been studied in neurological diseases; however, there is limited information linking brain morphological characteristics, QoL, and cognition. Human behavior and perception are associated with specific brain areas that interact through diffuse electrochemical networking. We used magnetic resonance imaging (MRI) to analyze the brain region volume (BRV) correlation with the scores of Rand’s 36-item Short Form Survey (SF-36) and cognitive domains (memory and dementia status). We analyzed data from 420 adult participants in the Maracaibo Aging Study (MAS). Principal component analysis with oblimin axis rotation was used to gather redundant information from brain parcels and SF-36 domains. Canonical correlation was used to analyze the relationships between SF-36 domains and BRV (adjusted for intracranial cavity), as well as sex, age, education, obesity, and hypertension. The average age (±SD) of subjects was 56 ± 11.5 years; 71% were female; 39% were obese; 12% had diabetes, 52% hypertension, and 7% dementia. No sex-related differences were found in memory and orientation scores, but women had lower QoL scores. The 1st and 2nd canonical correlation roots support the association of SF-36 domains (except social functioning and role emotional) and total brain volume, frontal lobe volume, frontal pole, lateral orbital lobe, cerebellar, and entorhinal areas. Other variables, including age, dementia, memory score, and systolic blood pressure, had a significant influence. The results of this study demonstrate significant correlations between BRV and SF-36 components, adjusted for covariates. The frontal lobe and insula were associated with the mental health component; the lateral-orbital frontal lobe and entorhinal area were correlated with the physical component.

Recent research suggests that infection with Onchocerca volvulus induces neurocognitive decline. This study sought to compare the cognitive outcomes of elderly persons based on onchocerciasis infection status and report the overall prevalence of dementia in the rural Ntui Health District in Cameroon. A community-based approach was used to recruit 103 participants aged ≥60 years. Dementia screening was done using the Community Screening Interview for Dementia (CSID) tool with a cut-off value of ≤29.5. O. volvulus infection was determined via microscopic examination of skin snips and serological testing of Ov16 antibodies using rapid diagnostic tests. Overall, the prevalence of dementia was 10.7%. Among the tested individuals, 17.9% (15/84) and 62.1% (41/66) were positive for O. volvulus and Ov16 antibodies, respectively. A multivariable linear regression model of CSID scores found a significant positive association with education level (8.654; 95% CI: 2.0870 to 15.222). However, having a positive skin snip for O. volvulus (−3.399; 95% CI: −6.805 to 0.007) and inhaling tobacco (−5.441; 95% CI: −9.137 to −1.744) tended to lower the CSID scores. Ongoing onchocerciasis transmission in the Ntui Health District may constitute a risk factor for dementia. Strengthening onchocerciasis elimination and adopting healthier lifestyles would contribute to dementia prevention among the elderly residing in endemic communities.

To provide evidence of ergodicity in the patho-connectome of temporal lobe epilepsy and to motivate meta-connectomic biomarker development for translational/clinical applications.

Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations. The South Texas Alzheimer's Disease Research Center, with efforts from the National Institutes of Health and the Global Brain Health Institute, has partnered with the Brain Research Africa Initiative to develop the African Initiative on Bioinformatics Online Training in Neurodegenerative Disease (AI-BOND). AI-BOND is a comprehensive and accessible training program, the aim of which is to advance biostatistics and bioinformatics expertise in Africa in studying neurodegenerative diseases. This expertise is essential to enable African scientists to utilize the extensive AD/ADRD data and enhance the continent's ability to contribute to global research efforts in this field. The training addresses the gap in analyzing neurodegenerative disease data by providing skills and knowledge in genetic epidemiology, biostatistics, and bioinformatics to African students and researchers. This innovative online training program will last 6 months and provide training in skill sets R, SAS, and Python programing, genome-wide association studies, genomics, transcriptomics, proteomics, metabolomics, microbiome analysis, and advanced statistical methods. Additional training will include study design and manuscript and grant writing. The first cohort of the AI-BOND program will graduate in June 2024. The AI-BOND program is expected to build research computational capacities in Africa that will improve the ability of graduates to conduct and utilize large-scale studies, with the goal of curbing the growing incidence of neurodegenerative diseases in Africa.

This cohort study of applicants to US MD-PhD programs examines the association of application outcomes with family income.

A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD ( p values < 0.001), as well as better executive function ( p values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and β-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.

AbstractDementia is a global public health problem with increasing prevalence and incidence worldwide. The African continent is expected to bear the biggest brunt of the burden of dementia by 2050 because of the rapid demographic changes, including rapid population growth, an increase in life expectancy, and ageing. However, French-speaking Sub-Saharan African (FS-SSA) countries are underrepresented in research on dementia in Africa. While the reasons are diverse and complex, linguistic and cultural barriers to research, disproportionately affect these countries and may be significant factors. Any efforts, therefore, to redress the burden of dementia in Africa must consider the specific demographic, cultural, and linguistic characteristics of FS-SSA countries. This scoping review explores the current state of knowledge in dementia and cognitive impairment in Sub-Saharan Africa, highlighting research gaps and specific patterns unique to FS-SSA Africa. We identify pathways for research to bridge the knowledge gaps on dementia in FS-SSA as part of the global endeavor to tackle dementia worldwide.