Although cognitively normal, brain aging in older adults occurs in a highly heterogeneous manner: it undergoes a wide range of abnormal neural changes that are not clinically evident. One of these abnormal neural changes is an accumulation of beta-amyloid, a pathological hallmark of Alzheimers disease (AD). Approximately 20-35% of cognitively normal older adults were shown to harbor a high level of Abeta deposition, equivalent to the level of AD patients, and brain systems supporting memory were shown to be particularly vulnerable to the effect of Abeta deposition. Using amyloid PET, glucose metabolism PET, and functional magnetic resonance imaging (fMRI), we demonstrated that differential neural plasticity occurs in response to aging and Abeta deposition in cognitively normal elderly in both regional activity and functional synchrony across the frontoparietal control regions and medial temporal lobes implicated in episodic memory.
Not only functional alterations described above but also neuromorphological changes occur with aging and Abeta deposition. In a set of studies, we examined changes in brain structure using gray matter volume and cortical thickness. Independent of Abeta deposition, a substantial aging-related reduction in gray matter volume and cortical thickness was found in most of brain regions, while Abeta-related gray matter atrophy was additionally found in frontal and parietal cortices and hippocampus. Among these regions undergoing gray matter atrophy, contributions of gray matter volume to cognition in older adults were more regionally specific, but the structure-cognition relationship was different dependent upon the level of Abeta deposition: A fronto-striatal network was related to cognition in older adults without Abeta deposition, while a hippocampal network was related to cognition in older adults with Abeta deposition. These findings contribute to a growing movement within cognitive aging research to better understand aging-related neural constraints that are driven by more heterogeneous etiologies than previously thought and their differential impact on cognition.
Considering that a relatively large proportion of cognitively normal elderly presents with Abeta deposition, it is not clear to what extent age and Abeta deposition contribute to cognitive changes in normal older adults. In a series of studies, we found that regardless of Abeta deposition, older adults, compared to young controls, show poorer performance in visual episodic memory and executive functions while performance in verbal episodic memory and semantic memory is preserved. Abeta-positive older adults, however, showed greater cognitive decline compared to Abeta-negative older adults, suggesting that even within a normal range of cognition, Abeta deposition is detrimentally associated with cognitive functions in normal older adults. In collaboration with researchers at Harvard/MGH, we further showed a significantly negative relationship between amyloid and cognition in a meta-analysis conducted on a large sample (7140 subjects) collapsing across 64 published studies.
A degree of the relationship between brain aging and cognition, however, seems to vary across individuals. In a set of studies, we showed that the observed relationship between Abeta deposition and cognition was moderated by a level of neural integrity such as metabolic rates and that cognitively stimulating activities across the lifetime affect the degree of AD pathology during aging.
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