An active or higher cognitive lifestyle is generally considered to be associated with diminished risk for dementia, but the underlying mechanisms are not well characterized. Possible mechanisms are thought to include disease modification, neuroprotection, and compensation.
Disease modification predicts that individuals with a more active cognitive lifestyle should have less Alzheimer pathology at death. Neuroprotection predicts that a more active cognitive lifestyle will be associated with a greater number of healthy neurons for a given level of Alzheimer pathology. Compensation predicts that a more active cognitive lifestyle will result in neurotrophic microstructural changes in mid-prefrontal brain areas.
Study subjects came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study. The brains of 329 individuals with cognitive lifestyle data were available for neuropathological assessment. A subsample of 72 subjects was selected for more detailed quantitative histology in the hippocampus and Brodmann area 9.
The study results suggest that a cognitively active lifestyle may reduce the incidence of clinical dementia, possibly through effects on silent cerebrovascular disease or compensatory prefrontal brain mechanisms, but not through reducing amyloid or tau pathology. No group differences were evident in hippocampal neuronal density. In Brodmann area 9, cognitively active individuals had significantly greater neuronal density, as well as correlated increases in cortical thickness. This study is consistent with some previous reports but is in conflict with a recent PET imaging study that found an association between higher lifetime cognitive engagement and low beta-amyloid deposit in the brain. The authors suggest that complex cognitive activity over the lifespan may protect against dementia through multiple biological pathways.
Valenzuela MJ, Matthews FE, Brayne C, Ince P, Halliday G, Kril JJ, Dalton MA, Richardson K, Forster G, Sachdev PS; Medical Research Council Cognitive Function and Ageing Study: Multiple biological pathways link cognitive lifestyle to protection from dementia. Biological Psychiatry 71(9): 783-791 (2012).
