Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change

Area of Science:

• Neuroscience
• Gerontology
• Cognitive Aging

Background:

• Episodic memory loss in aging is linked to brain atrophy, but the precise relationship is unclear.
• Aging and Alzheimer's Disease (AD) genetic risk accelerate brain decline, but their impact on memory loss beyond atrophy is unknown.

Purpose of the Study:

• To investigate the association between brain structure decline and episodic memory decline in aging.
• To determine if age and genetic risk for AD modify this brain-memory association.
• To assess if memory decline correlates with global or regional brain atrophy.

Main Methods:

• Mega-analysis of 13 longitudinal datasets (3737 healthy adults, 10,343 MRI scans, 13,460 memory assessments).
• Examined nonlinear relationships between brain atrophy and memory decline.
• Assessed the influence of age and APOE ε4 genotype on these associations.

Main Results:

• A nonlinear association exists between memory decline and brain atrophy, most prominent in individuals with accelerated brain structural decline.
• Associations are strongest in the hippocampus but also involve widespread cortical and subcortical regions.
• The brain-memory associations strengthen with age, becoming moderate in individuals in their eighties. APOE ε4 carrier status did not affect the change-change associations.

Conclusions:

• Common macrostructural substrates underlie memory function in older adults, vulnerable to various age-related factors.
• Memory decline is associated with widespread brain atrophy, not just localized changes.
• While aging intensifies the link between brain atrophy and memory loss, genetic risk for AD does not specifically alter this relationship in cognitively healthy individuals.