Study investigates the link between gray matter and white matter neurodegeneration in subjective cognitive decline

Reviewed by Emily Henderson, B.Sc.Oct 11 2021

Aging-US published "The interplay between gray matter and white matter neurodegeneration in subjective cognitive decline" which reported that subjective cognitive complaints were assessed through 9 questions covering amnestic and non-amnestic cognitive domains. In these authors' cohorts, 123 individuals endorsed from one to six subjective cognitive complaints, while 102 individuals reported zero complaints.

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.

Multiple pathologies can co-exist in cognitively unimpaired individuals, causing neurodegeneration years before the onset of cognitive decline."

Dr. Nira Cedres, The Karolinska Institutet

Increasing research is trying to ascertain whether individuals are able to subjectively detect such neurodegeneration, motivating the emergence of concepts like subjective cognitive decline, as a risk factor for dementia. Several studies showed that SCD may be a harbinger of Alzheimer's disease. However, community-based studies show that SCD can also be associated with cerebrovascular disease, age-related tauopathy, and emotional factors such as depressive symptomatology.

While some authors reported reduced GM volume or thickness in hippocampus, precuneus, cingulum, and frontal cortex in SCD individuals compared with healthy controls, other authors reported no differences or even increased GM volume in the fusiform gyrus and occipital areas in SCD.

In addition, previous studies operationalized SCD mostly based on episodic memory complaints and had a strong focus on AD. Hong et al. investigated 46 SCD patients, of which 19 had a high risk of progressing to AD and 27 had a low risk of progressing to AD based on age, APOE genotype, and cognitive performance. Using DTI, Hong et al. showed that SCD patients at a high risk of progressing to AD had greater neurodegeneration in frontotemporal WM areas, while no differences were found in cortical thickness.

The overall goal of the current study was to extend the previous research on GM and WM neurodegeneration in SCD.

The Cedres Research Team concluded in their Aging-US Research Output that this study is one of the few in investigating the association between GM and WM neurodegeneration in SCD. These data suggest an association between neurodegeneration processes affecting the GM and WM in SCD individuals. However, GM neurodegeneration seemed to have a stronger contribution to SCD in our community-based cohort, highlighting brain areas that are typically not targeted by AD. This finding suggests the contribution of non-AD pathologies to SCD and encourages that future studies extend imaging analysis to brain areas other than those typically involved in AD.