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Early Cortical Microstructural Changes in Aging Are Linked to Vulnerability to Alzheimer's Disease Pathology. | LitMetric

AI Article Synopsis

  • Early identification of Alzheimer's disease risk is vital, as structural changes in the brain can indicate neurodegeneration, with cortical thickness being a macrostructural measure and cortical mean diffusivity indicating microstructural changes.
  • A study of 194 adults over 5 to 6 years linked microstructural changes to patterns of tau deposition related to Alzheimer's, showing those changes correlate with greater declines in memory function.
  • The findings suggest that monitoring cortical microstructural changes might be more effective for early identification of Alzheimer's risk than focusing solely on macrostructural changes associated with normal aging processes.

Article Abstract

Background: Early identification of Alzheimer's disease (AD) risk is critical for improving treatment success. Cortical thickness is a macrostructural measure used to assess neurodegeneration in AD. However, cortical microstructural changes appear to precede macrostructural atrophy and may improve early risk identification. Currently, whether cortical microstructural changes in aging are linked to vulnerability to AD pathophysiology remains unclear in nonclinical populations, who are precisely the target for early risk identification.

Methods: In 194 adults, we calculated magnetic resonance imaging-derived maps of changes in cortical mean diffusivity (microstructure) and cortical thickness (macrostructure) over 5 to 6 years (mean age: time 1 = 61.82 years; time 2 = 67.48 years). Episodic memory was assessed using 3 well-established tests. We obtained positron emission tomography-derived maps of AD pathology deposition (amyloid-β, tau) and neurotransmitter receptors (cholinergic, glutamatergic) implicated in AD pathophysiology. Spatial correlational analyses were used to compare pattern similarity among maps.

Results: Spatial patterns of cortical macrostructural changes resembled patterns of cortical organization sensitive to age-related processes (r = -0.31, p < .05), whereas microstructural changes resembled the patterns of tau deposition in AD (r = 0.39, p = .038). Individuals with patterns of microstructural changes that more closely resembled stereotypical tau deposition exhibited greater memory decline (β = 0.22, p = .029). Microstructural changes and AD pathology deposition were enriched in areas with greater densities of cholinergic and glutamatergic receptors (ps < .05).

Conclusions: Patterns of cortical microstructural changes were more AD-like than patterns of macrostructural changes, which appeared to reflect more general aging processes. Microstructural changes may better inform early risk prediction efforts as a sensitive measure of vulnerability to pathological processes prior to overt atrophy and cognitive decline.

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Source
http://dx.doi.org/10.1016/j.bpsc.2024.05.012DOI Listing

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