The Interplay Between Gray Matter and White Matter Neurodegeneration in Subjective Cognitive Decline

Abstract

AIMS: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM. METHODS: We included 225 cognitively unimpaired individuals from a community-based cohort, of whom 123 endorsed one or more subjective cognitive complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration.RESULTS: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to the complaints, but the contribution of cortical thinning to SCD was stronger.CONCLUSIONS: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer’s disease (AD). Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.

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

“…Altogether, our results suggest that the variability in depressive symptomatology in our cohort may be related to emotional factors rather than cerebrovascular disease or age-related factors. Moreover, despite its strong association with SCC, depressive symptomatology seems to just co-exist with SCD in our cohort, without influencing associations of SCC with markers of cerebrovascular disease or, as demonstrated in previous studies using the same cohort, with markers of gray matter degeneration (Cedres et al, 2019 , 2020a ) or clinical-cognitive status (Diaz-Galvan et al, 2021 ). Hence, SCD in our cohort does not seem to merely reflect emotional factors, as traditionally postulated (Apolinario et al, 2013 ; Yates et al, 2015 ; Burmester et al, 2016 ), but may rather reflect neurodegeneration and subclinical cognitive decline.…”

“…For example, DTI has been proposed as a marker to monitor the progression of cerebrovascular disease (Fu et al, 2012 ). Both WMSA and DTI alterations have been separately associated with depression (Murphy et al, 2007 ; Allan et al, 2016 ) and SCD (Wang et al, 2012 ; Selnes et al, 2013 ; Li et al, 2016 ; Cedres et al, 2019 , 2020a ; Ohlhauser et al, 2019 ). However, little is known about the association between cerebrovascular disease, depressive symptomatology, and SCD.…”

Association of Cerebrovascular and Alzheimer Disease Biomarkers With Cholinergic White Matter Degeneration in Cognitively Unimpaired Individuals

“…greater WML volumes 4,28 , age was not included as a covariate in the models since it was controlled from the design (i.e. all participants were 70 years old).…”

“…R2 was computed to assess the quality of the RF models. Although aging is associated with WM neurodegeneration and greater WML volumes, 4,31 age was not included as a covariate in the models because it was controlled from the design (i.e., all participants were aged 70 years). For completeness of information, we also report Pearson correlation coefficients among the predictor variables included in the RF models and independent sample t tests for categorical variables that resulted important in the RF analysis.…”

Cerebrovascular disease and depressive symptomatology in individuals with subjective cognitive decline: A community‐based study

“…For example, DTI has been proposed as a marker to monitor the progression of cerebrovascular disease (Fu et al, 2012). Both WMSA and DTI alterations have been separately associated with depression (Murphy et al, 2007;Allan et al, 2016) and SCD (Wang et al, 2012;Selnes et al, 2013;Li et al, 2016;Cedres et al, 2019Cedres et al, , 2020aOhlhauser et al, 2019). However, little is known about the association between cerebrovascular Abbreviations: ACME, average causal mediation effect; AD, Alzheimer's disease; ADE, average direct effect; BDI, Beck's Depression Inventory; BDRS, Blessed Dementia Rating Scale; CVD, cerebrovascular disease; DTI, diffusion tensor imaging; FAQ, Functional Activity Questionnaire; FSPGR, Fast Spoiled Gradient Echo; GDS, Geriatric Depression Scale; GENIC, Grupo disease, depressive symptomatology, and SCD.…”