Sensitivity of the African neuropsychology battery memory subtests and learning slopes in discriminating APOE 4 and amyloid pathology in adult individuals in the Democratic Republic of Congo.

Background: The current study examined the sensitivity of two memory subtests and their corresponding learning slope metrics derived from the African Neuropsychology Battery (ANB) to detect amyloid pathology and APOEε4 status in adults from Kinshasa, the Democratic Republic of the Congo. Methods: 85 participants were classified for the presence of ß-amyloid pathology and based on allelic presence of APOEε4 using Simoa. All participants were screened using CSID and AQ, underwent verbal and visuospatial memory testing from ANB, and provided blood samples for plasma Aß42, Aß40, and APOE proteotype. Pearson correlation, linear and logistic regression were conducted to compare amyloid pathology and APOEε4 status with derived learning scores, including initial learning, raw learning score, learning over trials, and learning ratio. Results: Our sample included 35 amyloid positive and 44 amyloid negative individuals as well as 42 without and 39 with APOEε4. All ROC AUC ranges for the prediction of amyloid pathology based on learning scores were low, ranging between 0.56-0.70 (95% CI ranging from 0.44-0.82). The sensitivity of all the scores ranged between 54.3-88.6, with some learning metrics demonstrating good sensitivity. Regarding APOEε4 prediction, all AUC values ranged between 0.60-0.69, with all sensitivity measures ranging between 53.8-89.7. There were minimal differences in the AUC values across learning slope metrics, largely due to the lack of ceiling effects in this sample. Discussion: This study demonstrates that some ANB memory subtests and learning slope metrics can discriminate those that are normal from those with amyloid pathology and those with and without APOEε4, consistent with findings reported in Western populations.

The Association of Alzheimer's Disease-Related Blood-Based Biomarkers with Cognitive Screening Test Performance in the Congolese Population in Kinshasa.

BACKGROUND: Alzheimer's disease (AD), the most common cause of dementia, poses a significant global burden. Diagnosis typically involves invasive and costly methods like neuroimaging or cerebrospinal fluid (CSF) biomarker testing of phosphorylated tau (p-tau) and amyloid-ß42/40 (Aß42/40). Such procedures are especially impractical in resource-constrained regions, such as the Democratic Republic of Congo (DRC). Blood-based biomarker testing may provide a more accessible screening opportunity. OBJECTIVE: This study aims to examine if AD-related blood-based biomarkers are associated with cognitive test performance in the Congolese population, where limited research has been conducted. METHODS: In this cross-sectional study of 81 Congolese individuals, cognitive assessments (Alzheimer's Questionnaire (AQ) and Community Screening Interview for Dementia (CSID)) distinguished dementia cases from controls. Blood draws were taken to assess p-tau 181 and Aß42/40 biomarkers. Relationships between the biomarkers and cognitive performance were analyzed using multiple linear regression models. RESULTS: Lower plasma Aß42/40 was significantly associated with lower CSID scores and higher AQ scores, indicative of AD (p < 0.001). These relationships were observed in healthy controls (CSID p = 0.01, AQ p = 0.03), but not in dementia cases. However, p-tau 181 did not exhibit significant associations with either measure. Factors such as age, sex, education, presence of APOEɛ4 allele, did not alter these relationships. CONCLUSIONS: Understanding relationships between AD-related screening tests and blood biomarkers is a step towards utilization of blood-based biomarker tests as a screening tool for AD, especially in resource-limited regions. Further research should be conducted to evaluate blood biomarker test efficacy in larger samples and other populations.

Association of plasma biomarkers with cognitive function in persons with dementia and cognitively healthy in the Democratic Republic of Congo.

Introduction: This study investigates whether plasma biomarkers (Aß42/40 and p-tau 181), APS, as well as apolipoprotein E (APOE) proteotype predict cognitive deficits in elderly adults from the Democratic Republic of Congo. Methods: Forty-four with possible AD (pAD) and 41 healthy control (HC) subjects were screened using CSID and AQ, underwent cognitive assessment with the African Neuropsychology Battery (ANB), and provided blood samples for plasma Aß42, Aß40, Aß42/40, and APOE proteotype. Linear and logistic regression were used to evaluate the associations of plasma biomarkers with ANB tests and the ability of biomarkers to predict cognitive status. Results: Patients with pAD had significantly lower plasma Aß42/40 levels, higher APS, and higher prevalence of APOE E4 allele compared to HC. Groups did not differ in levels of Aß40, Aß42, or P-tau 181. Results showed that Aß42/40 ratio and APS were significantly associated with African Naming Test (ANT), African List Memory Test (ALMT), and African Visuospatial Memory Test (AVMT) scores, while the presence of APOE E4 allele was associated with ANT, ALMT, AVMT, and APT scores. P-tau 181 did not show any significant associations while adjusting for age, education, and gender. APS showed the highest area under the curve (AUC) value (AUC = 0.78, 95% confidence interval [CI]: 0.68-0.88) followed by Aß42/40 (AUC = 0.75, 95% CI: 0.66-0.86) and APOE E4 (AUC = 0.69 (CI 0.57-0.81) in discriminating pAD from HC. Discussion: These results demonstrate associations between select plasma biomarker of AD pathology (Aß42/40), APS, and APOE E4 allele) and ANB test scores and the ability of these biomarkers to differentiate pAD from cognitively normal SSA individuals, consistent with findings reported in other settings.

Association Between Hippocampal Volume and African Neuropsychology Memory Tests in Adult Individuals with Probable Alzheimer's Disease in Democratic Republic of Congo.

BACKGROUND: Western studies indicate potential associations between hippocampal volume and memory in the trajectory of Alzheimer's disease (AD). However, limited availability of neuroimaging technology and neuropsychological tests appropriate for sub-Saharan African (SSA) countries makes it difficult to establish neuroanatomical associations of hippocampus and memory in this locale. OBJECTIVE: This study examined hippocampal volumes and memory in healthy control (HC) and probable AD groups in the Democratic Republic of Congo (DRC). METHODS: Forty-six subjects with probable AD and 29 HC subjects were screened using the Community Instrument for Dementia and the Alzheimer Questionnaire. Participants underwent neuroimaging in Kinshasa, DRC, and memory was evaluated using the African Neuropsychology Battery (ANB). Multiple linear regression was used to determine associations between hippocampal volumes and memory. RESULTS: Patients with probable AD performed significantly worse than HCs on ANB memory measures, and exhibited greater cerebral atrophy, which was significantly pronounced in the medial temporal lobe region (hippocampus, entorhinal cortex). Both AD and HC subjects exhibited high rates of white matter hyperintensities compared to international base rate prevalence, which was significantly worse for probable AD. Both also exhibited elevated rates of microhemorrhages. Regression analysis demonstrated a significant association between hippocampal volume and ANB memory tests. Hippocampal atrophy discriminated probable AD from the HC group. CONCLUSIONS: This study establishes the feasibility of conducting neuroimaging research in the SSA, demonstrates many known neuroimaging findings in probable AD patients hold up using culturally appropriate memory tasks, and suggest cardiovascular problems are a greater issue in SSA than in Western countries.

Exploring factors contributing to caregiver burden in family caregivers of congolese adults with suspected dementia.

INTRODUCTION: Predicting caregiver burden in individuals with suspected dementia - is critical due to the debilitating nature of these disorders and need for caregiver support. While some examination of the factors affecting burden has been undertaken in Sub-Saharan Africa, each country presents with its own unique challenges and obstacles. This pilot study investigates predictors of caregiver burden in family caregivers of individuals with suspected dementia living in the Democratic Republic of the Congo (DRC). METHODS: Linear and multiple regression analyses were conducted to explore factors associated with caregiver burden in 30 patient-caregiver dyads with the Zarit Burden Interview (ZBI) for caregiver burden evaluation. Cognitive impairments of patients were assessed using the Community Screening Instrument for Dementia, Alzheimer's Questionnaire (AQ), the African Neuropsychology Battery, and the Neuropsychiatric Symptoms Inventory (NPI). RESULTS: Average caregiver burden on the ZBI was 36.1 (SD = 14.6; range = 12-58). Greater impairments in patient cognition (orientation, visuospatial, memory, executive functioning), fragility, and neuropsychiatric symptoms (delirium, agitation, depression) were predictive of caregiver burden. After controlling for AQ scores and caregiver gender, greater symptoms of depression, and worse performances on verbal memory and problem solving were associated with greater caregiver burden. CONCLUSION: Worsening patient fragility, cognition, functioning, and neuropsychiatric symptoms influenced caregiver burden in caregivers of individuals with suspected cognitive impairment in the DRC. These findings are consistent with the prior literature. Future studies may wish to explore supportive factors and caregiver specific characteristics that buffer against perceived burden.

The Association of Alzheimer's Disease-related Blood-based Biomarkers with Cognitive Screening Test Performance in the Congolese Population in Kinshasa.

Background: Alzheimer's Disease (AD), the most common cause of dementia, poses a significant global burden. Diagnosis typically involves invasive and costly methods like neuroimaging or cerebrospinal fluid (CSF) biomarker testing of phosphorylated tau (p-tau) and amyloid-ß42/40 (Aß42/40). Such procedures are especially impractical in resource-constrained regions, such as the Democratic Republic of Congo (DRC). Blood-based biomarker testing may provide a more accessible screening opportunity. Objective: This study aims to examine if AD-related blood-based biomarkers are associated with cognitive test performance in the Congolese population, where limited research has been conducted. Methods: In this cross-sectional study of 81 Congolese individuals, cognitive assessments (Alzheimer's Questionnaire (AQ) and Community Screening Interview for Dementia (CSID)) distinguished dementia cases from controls. Blood draws were taken to assess p-tau 181 and Aß42/40 biomarkers. Relationships between the biomarkers and cognitive performance were analyzed using multiple linear regression models. Results: Lower plasma Aß42/40 was significantly associated with lower CSID scores and higher AQ scores, indicative of AD (p<0.001). These relationships were observed in healthy controls (CSID p=0.01, AQ p=0.03), but not in dementia cases. However, p-tau 181 did not exhibit significant associations with either measure. Factors such as age, sex, education, presence of APOE e4 allele, did not alter these relationships. Conclusion: Understanding relationships between AD-related screening tests and blood-biomarkers is a step towards utilization of blood-based biomarker tests as a screening tool for AD, especially in resource-limited regions. Further research should be conducted to evaluate blood biomarker test efficacy in larger samples and other populations.

Performance on the African neuropsychology battery using the learning ratio in a sample of healthy Congolese.

OBJECTIVE: Using the African Neuropsychology Battery (ANB), we seek to develop normative data by examining the demographic effects for two learning process scores: initial learning (Trial One) and learning ratio (LR, the percentage of items learned relative of to-be-learned material following Trial 1). METHODS: Healthy participants from the Democratic Republic of Congo completed the four memory tests of the ANB: the African Story Memory Test (ASMT), African List Memory Test (ALMT), African Visuospatial Memory Test (AVMT), and African Contextual Visuospatial Memory Test (ACVMT). We developed indices of learning for each subtest, as well as aggregate learning indices for Trial 1 and LR, and composite indices examining verbal, visual, contextual, and noncontextual learning, and grand indices comprising all four subtests. RESULTS: Trial 1 and LR scores each demonstrated acceptable intercorrelations across memory tests. We present normative data for Trial 1 and LR by age and education. CONCLUSION: These data provide normative standards for evaluating learning in Sub-Saharan Africa.

Prevalence of suspected dementia in a sample of adults living in Kinshasa-Democratic Republic of the Congo.

BACKGROUND: The prevalence of dementia in Sub-Saharan Africa, particularly in French-speaking countries, has received limited attention. This study investigates the prevalence and risk factors of suspected dementia in elderly adults in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: A community-based sample of 355 individuals over 65 years old was selected using multistage probability sampling in Kinshasa. Participants were screened using the Community Screening Instrument for Dementia, Alzheimer's Questionnaire, Geriatric Depression Scale, Beck Anxiety Inventory, and Individual Fragility Questionnaire, followed by clinical interview and neurological examination. Suspected dementia diagnoses were made based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria including significant cognitive and functional impairments. Prevalence and odds ratios (ORs) with 95% confidence interval (CI) were calculated using, respectively, regression and logistic regression. RESULTS: Among 355 participants (mean age 74, SD = 7; 51% male), the crude prevalence of suspected dementia was 6.2% (9.0% in women and 3.8% in men). Female sex was a significant factor associated with suspected dementia [OR = 2.81, 95% CI (1.08-7.41)]. The prevalence of dementia increased with age (14.0% after 75 years and 23.1% after 85 years), with age being significantly associated with suspected dementia [OR = 5.42, 95% CI (2.86-10.28)]. Greater education was associated with a lower prevalence of suspected dementia [OR = 2.36, 95% CI (2.14-2.94), comparing those with ≥7.3 years of education to those with <7.3 years of education]. Other factors associated with the prevalence of suspected dementia included being widowed (OR = 1.66, 95% CI (1.05-2.61), being retired or semi-retired (OR = 3.25, 95% CI (1.50-7.03)], a diagnosis of anxiety [OR = 2.56, 95% CI (1.05-6.13)], and death of a spouse or a relative after age 65 [OR = 1.73, 95% CI (1.58-1.92)]. In contrast, depression [OR = 1.92, 95% CI (0.81-4.57)], hypertension [OR = 1.16, 95% CI (0.79-1.71)], body mass index (BMI) [OR = 1.06, 95% CI (0.40-2.79)], and alcohol consumption [OR = 0.83, 95% CI (0.19-3.58)] were not significantly associated with suspected dementia. CONCLUSIONS: This study found a prevalence of suspected dementia in Kinshasa/DRC similar to other developing countries and Central African countries. Reported risk factors provide information to identify high-risk individuals and develop preventive strategies in this setting.

Sensitivity of memory subtests and learning slopes from the ADAS-Cog to distinguish along the continuum of the NIA-AA Research Framework for Alzheimer's Disease.

Despite extensive use of the Alzheimer's Disease (AD) Assessment Scale - Cognitive Subscale (ADAS-Cog) in AD research, exploration of memory subtests or process scores from the measure has been limited. The current study sought to establish validity for the ADAS-Cog Word Recall Immediate and Delayed Memory subtests and learning slope scores by showing that they are sensitive to AD biomarker status. Word Recall subtest and learning slope scores were calculated for 441 participants from the Alzheimer's Disease Neuroimaging Initiative (aged 55 to 90). All participants were categorized using the NIA-AA Research Framework - based on PET-imaging of ß-amyloid (A) and tau (T) deposition - as Normal AD Biomarkers (A-T-), Alzheimer's Pathologic Change (A + T-), or Alzheimer's disease (A + T+). Memory subtest and learning slope performances were compared between biomarker status groups, and with regard to how well they discriminated samples with (A + T+) and without (A-T-) biomarkers. Lower Word Recall memory subtest scores - and scores for a particular learning slope calculation, the Learning Ratio - were observed for the AD (A + T+) group than the other biomarker groups. Memory subtest and Learning Ratio scores further displayed fair to good receiver operator characteristics when differentiating those with and without AD biomarkers. When comparing across learning slopes, the Learning Ratio metric consistently outperformed others. ADAS-Cog memory subtests and the Learning Ratio score are sensitive to AD biomarker status along the continuum of the NIA-AA Research Framework, and the results offer criterion validity for use of these subtests and process scores as unique markers of memory capacity.

The Reliability of the African Neuropsychology Battery in Persons of African Descent.

OBJECTIVE: The African Neuropsychology Battery (ANB) includes eight culturally appropriate cognitive tests developed for use in the Congo and other sub-Saharan African populations. The current study examines the reliability of the ANB in three samples of participants of African descent. METHODS: Subjects were recruited in the United States and the Congo to participate in three studies of ANB internal consistency reliability (Study 1), test-retest reliability (Study 2), and interrater reliability for the two ANB measures (i.e., Visuospatial Memory and Proverb Tests) requiring examiner ratings of response adequacy (Study 3). Subjects were administered ANB tests of visuospatial perception, language, memory, abstract reasoning, and problem solving. We calculated Cronbach's alpha, corrected item-total correlations and mean inter-item correlations for internal consistency, Pearson product-moment correlations and intraclass correlation coefficients for test-retest reliability, and intraclass correlation coefficients for interrater reliability. RESULTS: The ANB tests had acceptable internal consistency (Cronbach's alphas ranging from .37 to .93). Across subtests, test-retest reliability coefficients ranged from .39 to .91, and intraclass correlation stability coefficients (ICCs) ranged from .39 to .82. Of the two ANB tests requiring interrater reliability, only the Proverb Test had a low ICC of .13, (confidence intervals: -.29 to .52). CONCLUSION: The present study demonstrated that most ANB tests show adequate reliability in participants of African descent. However, the scoring criteria of the African Proverb Test require revision in order to improve the interrater reliability of the measure.

The conceptualization and measurement of cognitive reserve using common proxy indicators: Testing some tenable reflective and formative models.

INTRODUCTION: The examination of cognitive reserve (CR) literature reveals a lack of consensus regarding conceptualization and pervasive problems with its measurement. This study aimed at examining the conceptual nature of CR through the analysis of reflective and formative models using eight proxies commonly employed in the CR literature. We hypothesized that all CR proxies would significantly contribute to a one-factor reflective model and that educational and occupational attainment would produce the strongest loadings on a single CR factor. METHOD: The sample consisted of 149 participants (82 male/67 female), with 18.1 average years of education and ages of 45-99 years. Participants were assessed for eight proxies of CR (parent socioeconomic status, intellectual functioning, level of education, health literacy, occupational prestige, life leisure activities, physical activities, and spiritual and religious activities). Primary statistical analyses consisted of confirmatory factor analysis (CFA) to test reflective models and structural equation modeling (SEM) to evaluate multiple indicators multiple causes (MIMIC) models. RESULTS: CFA did not produce compelling support for a unitary CR construct when using all eight of our CR proxy variables in a reflective model but fairly cogent evidence for a one-factor model with four variable proxies. A second three-factor reflective model based upon an exploratory principal components analysis of the eight proxies was tested using CFA. Though all eight indicators significantly loaded on their assigned factors, evidence in support of overall model fit was mixed. Based upon the results involving the three-factor reflective model, two alternative formative models were developed and evaluated. While some support was obtained for both, the model in which the formative influences were specified as latent variables appeared to best account for the contributions of all eight proxies to the CR construct. CONCLUSION: While the findings provide partial support for our hypothesis regarding CR as a one-dimensional reflective construct, the results strongly suggest that the construct is more complex than what can be captured in a reflective model alone. There is a need for theory to better identify and differentiate formative from reflective indicators and to articulate the mechanisms by which CR develops and operates.