Subjective cognitive decline is associated with longitudinal cerebral blood flow reductions and gray matter atrophy in older adults

Abstract

Background Subjective cognitive decline (SCD), a potential harbinger of Alzheimer’s disease (AD), has been cross‐sectionally associated with neurodegeneration and cerebrovascular disease markers on brain MRI. However, longitudinal associations are less clear with few existing studies that yield inconsistent findings. Here, we related baseline SCD to longitudinal structural and hemodynamic markers of brain health in older adults free of clinical dementia and stroke. Methods Vanderbilt Memory & Aging Project participants (n=299,72±7 years, 58% male) completed a baseline SCD protocol and multimodal 3T brain MRI, including T 1‐weighted imaging (grey matter volumes) and pseudo‐continuous arterial spin labeling (cerebral blood flow (CBF)) at baseline and multiple follow‐ups (18‐months, 3‐years, 5‐years). Baseline SCD (total and subdomain memory, language, and executive functioning scores) was longitudinally related to global and regional grey matter volumes and CBF (mL/100g/min). Linear mixed effects models, with random intercepts and slopes and a follow‐up time interaction, covaried for baseline age, sex, race/ethnicity, education, diagnosis, mood, and apolipoprotein E (APOE)‐e4 status. Grey matter volume models covaried for intracranial volume. CBF models covaried for associated tissue volume. Results Mean follow‐up time was 3.8 years. Higher total SCD predicted hippocampal volume reductions (p=0.04), increased inferior lateral ventricular volume (p<0.001; Figure 1A), and global CBF reductions (p<0.001; Figure 1B). Higher scores within each SCD domain predicted hippocampal volume reductions, increased inferior lateral ventricular volume, and global CBF reductions (p‐values<0.04). Higher executive functioning‐SCD related only to frontal and occipital CBF reductions (p‐values<0.003; Figure 1C) but not temporal CBF or lobar atrophy (p‐values>0.07). Language‐SCD predicted reduced frontal CBF (p=0.01; Figure 1D) and temporal lobe volume (p=0.02). Surprisingly, memory‐SCD was not associated with temporal lobe volume or CBF (p‐values>0.05). Sensitivity analyses excluding outliers revealed the same associations. Conclusions Higher baseline SCD predicted multiple pathways of longitudinal brain changes, including cerebral hemodynamics and volume loss within areas first affected by AD. Executive functioning‐SCD predicted hemodynamic changes and language‐SCD related to alterations within the frontal and temporal lobes. Results suggest the relevance of considering the type of SCD, as specific domains may predict different pathologies over time with important prognostic implications. Future research is needed to understand the clinical consequences of these findings.

Greater subjective cognitive decline severity is associated with worse memory performance and lower entorhinal cerebral blood flow in healthy older adults

“…Another community-based study also found higher CBF in the left parahippocampal gyrus of individuals with SCD compared to those without SCD (Wenyi Li et al, 2022), suggestive of neurovascular dysregulation (Hays et al, 2016; Østergaard et al, 2013; Wierenga et al, 2014). Moreover, a longitudinal study showed that baseline SCD (measured as a continuous variable in a community-based sample) was associated with reduced global CBF in older adults over a 3.8 year follow-up period (Kresge et al, 2020). Given the importance of CBF to maintaining brain health and supporting cognitive function, and its role as a potential early marker of cognitive decline (Hays et al, 2016; Rabin et al, 2017; Wierenga et al, 2014), research is needed to better understand if SCD is associated with CBF in older adults.…”

Sex and Education Modify the Association Between Subjective Cognitive Decline and Amyloid Pathology

“…One efficient and inexpensive method of screening and identifying patients at increased risk of AD is through utilizing measures of subjective cognitive decline (SCD). Higher levels of SCD have been associated with cognitive decline, 4,5 hippocampal atrophy, 6 changes in cerebral blood flow, 6 and progression to MCI and dementia. 7 Despite the utility of SCD in predicting AD-related brain and clinical changes, there are numerous factors beyond AD that can contribute to SCD and many clinical and demographic factors that may modify the ability of SCD to predict AD-related changes.…”