Cognitive and social lifestyle: links with neuropathology and cognition in late life

Abstract

Many studies report an association of cognitive and social experiential factors and related traits with dementia risk. Further, many clinical-pathologic studies find a poor correspondence between levels of neuropathology and the presence of dementia and level of cognitive impairment. The poor correspondence suggests that other factors contribute to the maintenance or loss of cognitive function, with factors associated with the maintenance of function referred to as neural or cognitive reserve. This has led investigators to examine the associations of cognitive and social experiential factors with neuropathology as a first step in disentangling the complex associations between these experiential risk factors, neuropathology, and cognitive impairment. Despite the consistent associations of a range of cognitive and social lifestyle factors with cognitive decline and dementia risk, the extant clinical-pathologic data find only a single factor from one cohort, linguistic ability, related to AD pathology. Other factors, including education, harm avoidance, and emotional neglect, are associated with cerebrovascular disease. Overall, the associations are weak. Some factors, such as education, social networks, and purpose in life, modify the relation of neuropathology to cognition. Finally, some factors such as cognitive activity appear to bypass known pathologies altogether suggesting a more direct association with biologic indices that promote person-specific differences in reserve and resilience. Future work will first need to replicate findings across more studies to ensure the veracity of the existing data. Second, effort is needed to identify the molecular substrates of neural reserve as potential mediators of the association of lifestyle factors with cognition.

Figure 1

Schematic representing three potential classes of mechanisms linking cognitive and social lifestyle factors with neuropathology and dementia. Lifestyle I is a direct disease effect on neuropathology such that it is directly associated with more or less pathology. Lifestyle II represents a modulatory effect such that the experiential factor alters the relation of pathology to cognition, i.e., increases or decreases the probability of dementia for any given level of neuropathology. Lifestyle III represents a pathway linking lifestyle to dementia that is unrelated to classic neuropathology.