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.
Highlights
Multiple pathologies can co-exist in cognitively unimpaired individuals, causing neurodegeneration years before the onset of cognitive decline [1]
We investigated 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 skeleton
We found that the association of WM neurodegeneration with a higher number of complaints was widespread across the WM skeleton, with a tendency to spare the occipital lobe
Summary
Multiple pathologies can co-exist in cognitively unimpaired individuals, causing neurodegeneration years before the onset of cognitive decline [1]. Previous studies revealed macrostructural neurodegeneration in the brain gray matter (GM) of SCD individuals, but the analyses were often limited to areas typically affected in AD These studies consistently found reduced volumes in the hippocampus and entorhinal cortex [14,15,16], and cortical thinning in medial temporal areas [17,18,19]. Some studies overcame this limitation by exploring the whole cortex using voxelbased morphometry or vertex-wise analysis in SCD [22,23,24,25,26,27,28,29]. Little is known about GM neurodegeneration potentially associated with complaints in non-memory cognitive domains
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