Abstract
The large majority of neuroimaging studies in Alzheimer’s disease (AD) patients have supported the idea that lifestyle factors may protect against the clinical manifestations of AD rather than influence AD neuropathological processes (the cognitive reserve hypothesis). This evidence argues in favor of the hypothesis that lifestyle factors act as moderators between AD pathology and cognition, i.e., through indirect compensatory mechanisms. In this review, we identify emerging evidence in cognitively normal older adults that relate lifestyle factors to established AD neuroimaging biomarkers. While some of these investigations are in agreement with the compensatory view of cognitive reserve, other studies have revealed new clues on the neural mechanisms underlying beneficial effects of lifestyle factors on the brain. Specifically, they provide novel evidence suggesting direct effects of lifestyle factors on AD neuropathological processes. We propose a tentative theoretical model where lifestyle factors may act via direct neuroprotective and/or indirect compensatory mechanisms. Importantly, we suggest that neuroprotective mechanisms may have a major role during early stages and compensatory mechanisms in later stages of the disease. In the absence of an effective treatment for AD and considering the potential of lifestyle factors in AD prevention, understanding the neural mechanisms underlying lifestyle effects on the brain seems crucial. We hope to provide an integrative view that may help to better understand the complex effects of lifestyle factors on AD neuropathological processes, starting from the preclinical stage.
Highlights
In the absence of effective treatments for Alzheimer’s disease (AD), new therapeutical approaches that may assist in preventing and/or delaying the onset of AD appear essential
Nowadays, growing neuroimaging evidence in cognitively normal individuals points to potential links between lifestyle factors and AD neuropathological expression (Figure 4B), which suggests that the effects of lifestyle might be exerted via both compensatory and neuroprotective mechanisms
While studies in AD patients point to lifestyle-related compensatory mechanisms, new evidence in cognitively normal elders with AD neuroimaging biomarkers and preclinical AD subjects suggests that lifestyle factors may directly impact the development of AD neuropathology
Summary
In the absence of effective treatments for Alzheimer’s disease (AD), new therapeutical approaches that may assist in preventing and/or delaying the onset of AD appear essential. These studies included: (i) samples of cognitively normal older adults with neuroimaging biomarker information (and CSF markers in some of them); or (ii) older adults considered to be at higher risk for AD (that may in part represent the preclinical AD stage), such as older adults showing pathological levels of Aβ deposition or carrying the ε4 allele of the Apolipoprotein (APOE) gene (the highest known genetic risk factor for sporadic AD) While some of these investigations are in agreement with the notion that lifestyle factors may have a modulatory effect on the brain, other studies provide new clues on the neural mechanisms underlying the effects of lifestyle factors on the brain and on the potential mechanisms underlying cognitive and brain reserve. Direct effects of lifestyle in key regions such as the hippocampus and the temporal lobe have found support in several cross-sectional studies
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