Brain structure and function as mediators of the effects of amyloid on memory

• Objective:The objective of this study was to test whether effects of -amyloid (A) pathology on episodic memory were mediated by metabolism and gray matter volume in the early stages of Alzheimer disease.Methods:This was a prospective cohort study. We measured baseline A (using florbetapir-PET), brain function (using fluorodeoxyglucose-PET), and brain structure (using MRI). A mediation analysis was performed to test whether statistical effects of A positivity on cross-sectional and longitudinal episodic memory were mediated by hypometabolism or regional gray matter volume in cognitively healthy controls (CN, n = 280) and mild cognitive impairment (MCI, n = 463).Results:Lower memory scores were associated with A positivity (CN, mildly; MCI, strongly), smaller gray matter volumes (CN, few regions, including hippocampus; MCI, widespread), and hypometabolism. Smaller volumes and hypometabolism mediated effects of A in MCI but not in CN. The strongest individual regions mediated up to approximately 25%. A combination of brain structure and function mediated up to approximately 40%. In several regions, gray matter atrophy and hypometabolism predicted episodic memory without being associated (at p < 0.05) with A positivity.Conclusions:Changes in brain structure and function appear to be, in part, downstream events from A pathology, ultimately resulting in episodic memory deficits. However, A pathology is also strongly related to memory deficits through mechanisms that are not quantified by these imaging measurements, and episodic memory decline is partly caused by Alzheimer disease-like brain changes independently of A pathology.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Keyword

PRECLINICAL ALZHEIMERS-DISEASE

MILD COGNITIVE IMPAIRMENT

ELDERLY

SUBJECTS

EPISODIC MEMORY

OLDER-ADULTS

ATROPHY

BIOMARKERS

DECLINE

DEPOSITION

PATHOLOGY

Clinical Neurology

Publication and Content Type

ref (subject category)

art (subject category)