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. Subjective cognitive complaints were assessed through 9 questions covering amnestic and non-amnestic cognitive domains. In our cohort, 123 individuals endorsed from one to six subjective cognitive complaints (i.e. they fulfilled the diagnostic criteria for SCD), while 102 individuals reported zero 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 complaints, but the contribution of cortical thinning to the number of complaints 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. Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.

Association of walking speed with cognitive function in Chinese older adults: A nationally representative cohort study

“…Several mechanisms may account for the link between walking speed and the risk of poorer cognitive function and slightly faster cognitive decline. First, neurodegeneration not only contributes to cognitive decline ( Cedres et al, 2021 ) but also to some extent affects walking abilities ( Tian et al, 2016 ). Some evidence has indicated that slow walking speed was associated with higher levels of amyloid β in key brain areas( Del Campo et al, 2016 ) as well as the changes in subcortical white matter and cortical gray matter volumes ( Holtzer et al, 2014 ).…”

Subjective Impairments in Olfaction and Cognition Predict Dissociated Behavioral Outcomes

“…The lack of association between SCD and objective olfaction, while present in the SCD + SOI group, might point to different underlying pathologies for each subgroup. In this population-based cohort, we hypothesized that the exclusive SCD presentation might represent an underlying subclinical pathology, presumably from a vascular origin ( Cedres et al, 2019 ; Diaz-Galvan, Cedres, et al, 2021 ), while the joint SCD + SOI group might be subclinically associated with other pathologies more strongly linked to olfaction, such as AD ( Duff et al, 2002 ) or Parkinson’s disease ( Doty, 2012 ). We base this speculation on the finding that SCD in the general population is associated with underlying cerebrovascular pathology ( Cedres et al, 2019 ; Diaz-Galvan, Cedres, et al, 2021 ) and an increased likelihood of progression to vascular dementia ( Slot, Sikkes, Berkhof, Brodaty, van der Flier, et al, 2019 ).…”

“…In this population-based cohort, we hypothesized that the exclusive SCD presentation might represent an underlying subclinical pathology, presumably from a vascular origin ( Cedres et al, 2019 ; Diaz-Galvan, Cedres, et al, 2021 ), while the joint SCD + SOI group might be subclinically associated with other pathologies more strongly linked to olfaction, such as AD ( Duff et al, 2002 ) or Parkinson’s disease ( Doty, 2012 ). We base this speculation on the finding that SCD in the general population is associated with underlying cerebrovascular pathology ( Cedres et al, 2019 ; Diaz-Galvan, Cedres, et al, 2021 ) and an increased likelihood of progression to vascular dementia ( Slot, Sikkes, Berkhof, Brodaty, van der Flier, et al, 2019 ). Individuals with vascular dementia rarely present olfactory deficits ( Duff et al, 2002 ), since the symptomatology is highly dependent on where the vascular lesions are located ( Alves et al, 2014 ).…”

“…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 ).…”

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

“…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.…”