Background:
This paper will review our work in the area linking complex mental activity and dementia risk, focusing on epidemiological evidence and potential underlying mechanisms based upon in vivo metabolic and structural neuroimaging.
Methods:
A quantitative parametric meta-analysis of cognitive dementia studies. Mechanistic studies include a longitudinal study of cognition and magnetic resonance imaging volumetry as well as a randomized control trial of a memory training intervention with pre- and postmagnetic resonance spectroscopy of the medial temporal, frontal and occipital lobe.
Results:
Meta-analysis of 22 cohort studies showed a significant reduction in risk for dementia incidence based on history of high complex mental activity (odds ratio: 0.54, confidence interval: 0.49–0.59). Longitudinal analysis found that a history of complex mental activity was significantly associated with a slower rate of hippocampal atrophy over 3 years after controlling for relevant confounders (P < 0.01). Furthermore, differential rates of hippocampal atrophy accounted for the different rates of cognitive decline in the high- and low-mental-activity groups. Systematized memory exercise selectivity increased phosphocreatine-creatine signal in the medial temporal lobe over our 5-week intervention.
Conclusions:
There is compelling epidemiological evidence that complex mental activity is associated with a lower risk for dementia and cognitive decline. We have found that part of this association may be mediated by differential hippocampal atrophy. This link was further supported by finding selectively increased phosphocreatine-creatine in the medial temporal lobe as a consequence of focused memory exercises, particularly because upregulation of this high-energy buffer system has a neuroprotective effect in mouse models of neurodegeneration.