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F5‐03‐03: RESISTANCE TO AD OVER THE LIFECOURSE
Author(s) -
Jagust William J.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.2978
Subject(s) - neuropathology , dementia , neuroimaging , cognition , neuroscience , psychology , amyloid (mycology) , cognitive reserve , biomarker , cognitive decline , medicine , gerontology , disease , pathology , cognitive impairment , biology , biochemistry
Background:It is generally believed that the neuropathology of AD proceeds inexorably in the presence of a relatively limited group of risk factors such as genetics and age, and that whether or not an individual ultimately expresses symptoms is largely a function of resilience in the face of this pathology. However, if one takes a broader view of the factors that lead to dementia, data suggest that a variety of factors over the lifespan actually may enhance or inhibit dementia related pathology and thus confer resistance. Methods: This talk reviews mechanisms underlying the development of dementia pathology, and how a variety of exposures operating over the lifespan might exacerbate or alleviate this pathology. Key to these studies are investigations of relationships between exposures and imaging outcomes reflecting pathology. Results:One of the determinants of deposition of b-amyloid in the brain is neural activity. In this situation, it is possible that lower levels of neural activity result in less Ab release over the lifespan. This lower Ab release should be associated with greater neural efficiency. Imaging research supports this model to some extent: more brain Ab (measured with PET) is associated with greater neural activity in cognitively normal older people, and lifetime cognitive engagement (presumably reflecting greater neural “training” and efficiency) is associated with less Ab. A gene x environment interaction has specifically noted these salutary lifelong cognitive engagement effects in ApoE4 carriers. Lifetime cognitive activity, and lifetime physical activity were also both associated with the volume of brain white matter lesions (WML) which were associated with a multimodal biomarker of neural integrity in AD-vulnerable brain regions that was in turn associated with global cognition. In addition, a number of studies have shown associations between vascular risk factors and brain Ab, with particular findings related to midlife vascular risk, hypertension, and hypercholesterolemia. Conclusions:Together these studies point to the possibility that lifelong exposures may affect brain b-amyloid deposition in older age. These exposures include cognitive engagement, physical activity, and cerebrovascular risk. Lifelong health habits offer potential for ameliorating AD risk by conferring resistance to pathology.