Lifespan Mental Activity Predicts Diminished Rate of Hippocampal Atrophy

Michael J Valenzuela,Perminder Sachdev,Wei Wen,Henry Brodaty,Xiaohua Chen,Olaf Sporns

doi:10.1371/journal.pone.0002598

Michael J Valenzuela, Perminder Sachdev + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0002598

Copy DOI

Abstract

ObjectiveEpidemiological studies suggest that complex mental activity may reduce the risk for dementia, however an underlying mechanism remains unclear. Our objective was to determine whether individual differences in lifespan complex mental activity are linked to altered rates of hippocampal atrophy independent of global measures of neurodegeneration.MethodsThirty seven healthy older individuals had their complex mental activity levels estimated using the Lifetime of Experiences Questionnaire (LEQ) and completed serial MRI investigations at baseline and three years follow-up. Hippocampal volume and semi-automatic quantitation of whole brain volume (WBV) and white matter hyperintensities (WMHs) were compared at both time points.ResultsHigher LEQ scores were correlated with hippocampal volume independent of covariates at the three year follow-up stage (r = 0.43, p = 0.012). Moreover, those with higher LEQ scores experienced less hippocampal atrophy over the follow-up period (r = 0.41, p = 0.02). High LEQ individuals had less than half the hippocampal volume decline of low LEQ individuals in a multivariate analysis (F = 4.47, p = 0.042). No parallel changes were found in measures of WBV and WMHs.ConclusionsHigh level of complex mental activity across the lifespan was correlated with a reduced rate of hippocampal atrophy. This finding could not be explained by general differences in intracranial volume, larger hippocampi at baseline, presence of hypertensive disease, gender or low mood. Our results suggest that neuroprotection in medial temporal lobe may be one mechanism underlying the link between mental activity and lower rates of dementia observed in population-based studies. Additional studies are required to further explore this novel finding.

Highlights

Epidemiological and clinical studies suggest that lifespan mental activity may be a significant modifiable protective factor in the development of dementia
Alzheimer’s disease (AD) transgenic rodent studies have produced mixed results: three groups have reported between 30–50% reduction in amyloid burden [8,9,10], but others have replicated a behavioral advantage and found either increased b-amyloid burden [11], or no change [12]
High Lifetime of Experiences Questionnaire (LEQ) individuals experienced an average loss of 3.6% of hippocampal volume over a three-year period, whilst low LEQ individuals exhibited more than twice this volumetric loss (8.3%)

Summary

Introduction

Epidemiological and clinical studies suggest that lifespan mental activity may be a significant modifiable protective factor in the development of dementia. Alzheimer’s disease (AD) transgenic rodent studies have produced mixed results: three groups have reported between 30–50% reduction in amyloid burden [8,9,10], but others have replicated a behavioral advantage and found either increased b-amyloid burden [11], or no change [12]. Differences between how these groups operationally defined their specific enrichment intervention may partly account for these divergent findings

Methods

Results

Discussion

Conclusion