Neuropsychiatric symptoms and lifelong mental activities in cerebral amyloid angiopathy - a cross-sectional study

Abstract

Background: While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted.

Methods: We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC). The number and severity of NPS were assessed using the Alzheimer's Disease (AD) Assessment Scale's (ADAS) noncognitive subscale. We applied different regression models exploring associations between NPS number or severity and group status (CAA vs. NC), CAA severity assessed with magnetic resonance imaging (MRI) or cognitive function (Mini-Mental State Examination (MMSE), ADAS cognitive subscale), adjusting for age, sex, years of education, arterial hypertension, AD pathology, and apolipoprotein E status. Mediation analyses were performed to test indirect effects of lifelong mental activities on CAA severity and NPS.

Results: Patients with CAA had 4.86 times (95% CI 2.20-10.73) more NPS and 3.56 units (95% CI 1.94-5.19) higher expected NPS severity than NC. Higher total CAA severity on MRI predicted 1.14 times (95% CI 1.01.-1.27) more NPS and 0.57 units (95% CI 0.19-0.95) higher expected NPS severity. More severe white matter hyperintensities were associated with 1.21 times more NPS (95% CI 1.05-1.39) and 0.63 units (95% CI 0.19-1.08) more severe NPS. NPS number (MMSE mean difference - 1.15, 95% CI -1.67 to -0.63; ADAS cognitive mean difference 1.91, 95% CI 1.26-2.56) and severity (MMSE - 0.55, 95% CI -0.80 to -0.30; ADAS cognitive mean difference 0.89, 95% CI 0.57-1.21) predicted lower cognitive function. Greater lifelong mental activities partially mediated the relationship between CAA severity and NPS (indirect effect 0.05, 95% CI 0.0007-0.13), and greater lifelong mental activities led to less pronounced CAA severity and thus to less NPS (indirect effect - 0.08, 95% CI -0.22 to -0.002).

Discussion: This study suggests that NPS are common in CAA, and that this relationship may be driven by CAA severity. Furthermore, NPS seem to be tied to lower cognitive function. However, lifelong mental activities might mitigate the impact of NPS in CAA.

Keywords: Alzheimer’s disease; Cerebral amyloid angiopathy; Depression; Lifelong mental activities; Magnetic resonance imaging; Neuropsychiatric symptoms; White matter hyperintensities.

Fig. 1

Mediation model testing indirect effects of lifelong mental activities on cerebral amyloid angiopathy (CAA) severity and neuropsychiatric symptom (NPS) number. CAA total score was the independent, NPS number the dependent variable and the lifetime of experiences questionnaire (LEQ) total score the mediator. Covariates were age, sex, years of education, arterial hypertension, Alzheimer’s disease pathology, apolipoprotein E status. a: effect of CAA severity on LEQ total score (-1.68, 95% confidence interval (CI) -3.24 to -0.12, p = 0.035). b: effect of LEQ total score on NPS number (-0.26, 95% CI -0.05 to -0.002, p = 0.033). c’: direct effect of CAA score on NPS number (0.22, 95% CI 0.04–0.39, p = 0.014). c: total effect of CAA score on NPS number (0.26, 95% CI 0.09–0.44, p = 0.003)