Association between neuropsychiatric symptoms and neurodegeneration-related plasma biomarkers in older adults with and without clinical dementia in the Democratic Republic of the Congo

Abstract

Introduction: Neuropsychiatric symptoms (NPS) are prevalent in dementia, but most studies focus on Western populations. This study examines the association between NPS and neurodegeneration-related plasma biomarkers in older adults with and without dementia in the Democratic Republic of the Congo (DRC).

Methods: Eighty-five individuals (≥65 years) underwent dementia adjudication using the Community Screening Instrument for Dementia (CSID) and Alzheimer's Questionnaire (AQ). Plasma biomarkers (amyloid β [Aβ] 42/40, phosphorylated-tau181 [p-tau181], neurofilament light [NfL], glial fibrillary acidic protein (GFAP), interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α]) were measured. NPS were assessed using the Geriatric Depression Scale (GDS), Beck Anxiety Inventory (BAI), and Neuropsychiatric Inventory Questionnaire (NPI) (for dementia cases). Logistic regressions examined associations between NPS and biomarkers, adjusting for age, sex, and education.

Results: NPS were common in dementia cases, with irritability (57.8%) and depression (90.7%) most frequent. GFAP was linked to irritability (odds ratio [OR] = 3.34, p = 0.01), and NfL and GFAP were associated with depressive symptoms (OR = 0.76, p = 0.04; OR = 1.98, p = 0.02, respectively).

Discussion: These findings highlight the burden of NPS in the DRC and suggest biomarker-driven mechanisms, emphasizing the need for further research in diverse populations.

Highlights: Identifies neuropsychiatric symptoms as early indicators of Alzheimer's disease (AD) progression. Examines associations between depression and AD biomarkers in preclinical and prodromal stages. Highlights the role of amyloid and tau pathology in depression-related cognitive decline. Discusses implications for early intervention and personalized treatment strategies.

Keywords: Congo; biomarkers; cognition; dementia; neuropsychiatric symptoms.

FIGURE 1

Flow chart of recruitment status from those assessed for eligibility at enrollment (n = 1432) to the individuals who were allocated to dementia (n = 45) and healthy controls (n = 40) who donated blood for biomarkers.

FIGURE 2

Scatterplots displaying the relationship between age and various Alzheimer's disease‐related biomarkers, including Aβ42/40, p‐tau181, Aβ42/p‐tau181, NfL, GFAP, TNF‐α, and IL‐10. Each plot includes a fitted regression line (red) and Pearson's correlation coefficient (r) summarizing the strength and direction of the association. Biomarker values were not transformed. Overall, the associations between age and biomarker levels ranged from negligible to moderate, with the strongest positive correlation observed for p‐tau181 (r = 0.320) and GFAP (r = 0.300). Aβ, amyloid β; GFAP glial fibrillary acidic protein; IL‐10, interleukin‐10; NfL, neurofilament light chain; p‐tau, phosphorylated tauTNF‐α, tumor necrosis factor‐alpha.

FIGURE 3

Boxplots of biomarker concentrations stratified by (left to right): (A) Gender (male vs. female), (B) APOE ε4 carrier status (noncarrier vs. carrier), and (C) Neurological status (healthy control vs. clinical dementia). Biomarkers shown include Aβ42/40, p‐tau181, Aβ42/p‐tau181, NFL, GFAP, TNF‐α, and IL‐10. Median values are labeled on each boxplot. This visualization highlights group differences in biomarker levels across demographic and clinical variables, including elevated p‐tau181 and GFAP among APOE ε4 carriers and individuals with clinical dementia. Aβ, amyloid β; APOE, apolipoprotein E; GFAP glial fibrillary acidic protein; IL‐10, interleukin‐10; NfL, neurofilament light chain; p‐tau, phosphorylated tau; TNF‐α, tumor necrosis factor‐alpha.

FIGURE 4

This figure illustrates the prevalence and demographic distribution of neuropsychiatric symptoms (NPS) across multiple domains: (1) Left panel: Bar plots show the proportion of NPS presence and absence by gender, (2) Middle panel: Boxplots depict the age distribution among individuals with and without each symptom, with median ages labeled, and (3) Right panel: Bar plots show NPS proportions stratified by APOE ε4 carrier status. The visualization suggests demographic variation in NPS expression, including a higher prevalence of depressive symptoms among females and APOE ε4 carriers. APOE, apolipoprotein E, NPS, neuropsychiatric symptoms.