Cerebrovascular Disease and Depressive Symptomatology in Individuals With Subjective Cognitive Decline: A Community-Based Study

Abstract

Subjective cognitive decline (SCD) may be the first sign of Alzheimer's disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. We investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We recruited 225 cognitively unimpaired individuals from a prospective community-based study [mean age (SD) = 54.64 (10.18); age range 35–77 years; 55% women; 123 individuals with one or more subjective cognitive complaints, 102 individuals with zero complaints]. SCD was assessed with a scale of 9 memory and non-memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. Cerebrovascular disease was assessed with magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD). We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD. We found that SCD was associated with more cerebrovascular disease, older age, and increased depressive symptomatology. In turn, depressive symptomatology was not associated with cerebrovascular disease. Variability in MD was mediated by WMSA burden, presumably reflecting cerebrovascular disease. We conclude that, in our community-based cohort, depressive symptomatology is associated with SCD but not with cerebrovascular disease. In addition, depressive symptomatology did not influence the association between cerebrovascular disease and SCD. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD individuals from the community.

The interplay between gray matter and white matter neurodegeneration in subjective cognitive decline

“…Both the internal capsule and posterior WM tracts receive dense cholinergic input, and increased MD in cholinergic WM pathways was associated with greater cerebrovascular disease and lower cognitive performance in our cohort [ 49 ]. Finally, as we showed in a recent study using the same cohort, the association between the number of subjective cognitive complaints and WM neurodegeneration was independent from depressive symptomatology [ 50 ], despite depressive symptomatology is consistently associated with SCD [ 9 , 12 , 13 ]. All together, these findings indicate that SCD is associated with WM neurodegeneration in certain regions that go beyond age- or depressive symptomatology-related effects.…”

“…Because multiple pathologies usually coexist in the brain of cognitively unimpaired individuals [ 53 , 54 ], future studies should unveil the pathologies underlying non-AD patterns of GM and WM neurodegeneration in SCD. Investigating pathologies such as cerebrovascular disease and tauopathies is warranted due to their contribution to SCD in community-based cohorts [ 11 , 49 , 50 , 55 ]. A limitation of our cohort is that we do not have biomarkers for amyloid-beta and tau-related pathologies.…”

Recent contributions to the field of subjective cognitive decline in aging: A literature review

“…Another study found that 34% of the variance in SCC reported during the COVID‐19 pandemic was explained by a combination of perceived stress, negative emotions, and poorer general physical health related to prolonged confinement or quarantine 123 . Certain medical conditions may also be associated with elevated reports of SCC and increased NPS, including migraines and cerebrovascular disease, although the study examining cerebrovascular disease found that NPS were more associated with perceived SCD than cerebrovascular disease itself 124,125 …”

Subjective Impairments in Olfaction and Cognition Predict Dissociated Behavioral Outcomes

“…Yet, SCD individuals have shown an increased risk for future cognitive impairment and dementia compared to non-SCD, independent of the origin of the sample (i.e., memory clinic or general population; Slot, Sikkes, Berkhof, Brodaty, van der Flier, et al, 2019 ). Furthermore, SCD has been associated with multiple underlying brain pathological markers, such as increased amyloidosis and tauopathies ( Buckley et al, 2017 ), gray and white matter neurodegeneration ( Cedres et al, 2021 ), and small vessel disease ( Diaz-Galvan, Cedres, et al, 2021 ). In fact, it has been shown that amnestic SCD (i.e., cognitive complaints referring to the memory domain) presents a brain atrophy pattern similar to that typically presented in Alzheimer’s disease (AD; Diaz-Galvan, Ferreira, et al, 2021 ).…”

“…Furthermore, SCD has been associated with multiple underlying brain pathological markers, such as increased amyloidosis and tauopathies ( Buckley et al, 2017 ), gray and white matter neurodegeneration ( Cedres et al, 2021 ), and small vessel disease ( Diaz-Galvan, Cedres, et al, 2021 ). In fact, it has been shown that amnestic SCD (i.e., cognitive complaints referring to the memory domain) presents a brain atrophy pattern similar to that typically presented in Alzheimer’s disease (AD; Diaz-Galvan, Ferreira, et al, 2021 ). On the other hand, the same study showed that nonamnestic SCD seems to be associated with increased underlying small vessel disease in the general population ( Diaz-Galvan, Ferreira, et al, 2021 ).…”