Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease

doi:10.1016/S1474-4422(05)70198-8

The Lancet Neurology

Volume 4, Issue 11, November 2005, Pages 705-711

https://doi.org/10.1016/S1474-4422(05)70198-8 Get rights and content

Summary

Background

Physical activity may help maintain cognitive function and decrease dementia risk, but epidemiological findings remain controversial. The aim of our study was to investigate the association between leisure-time physical activity at midlife and the subsequent development of dementia and Alzheimer's disease (AD).

Methods

Participants were randomly selected from the survivors of a population-based cohort previously surveyed in 1972, 1977, 1982, or 1987. 1449 persons (72·5%) age 65–79 years participated in the re-examination in 1998 (mean follow-up, 21 years). 117 persons had dementia and 76 had AD. Multiple logistic regression methods were used to analyse the association between leisure-time physical activity and dementia or AD.

Findings

Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD (odds ratio [OR] 0·48 [95% CI 0·25–0·91] and 0·38 [0·17–0·85], respectively), even after adjustments for age, sex, education, follow-up time, locomotor disorders, APOE genotype, vascular disorders, smoking, and alcohol drinking. The associations were more pronounced among the APOE ɛ4 carriers.

Interpretation

Leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life. Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals.

Introduction

Recent studies have shown that a large proportion of the population undertakes less physical activity than is necessary to maintain good health.¹ At the same time, the proportion of old people is increasing, and age-related diseases, such as dementia and Alzheimer's disease (AD), are becoming major public health problems. Interventions that could postpone the onset of AD even modestly would have a major effect on public health.²

Current data, epidemiological and experimental, suggest that physical exercise may promote brain health, and prevent or slow cognitive decline and development of dementia; however, results are conflicting.3, 4, 5, 6, 7 Prospective epidemiological studies have previously been done in cohorts of elderly people (baseline age >65 years), but had relatively short follow-up times (3–7 years), making them prone to biases attributable to subclinical dementia and other factors.5, 6, 7, 8, 9, 10, 11, 12 The aim of our study was to investigate whether leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life. We also investigated whether sex or the APOE ɛ4 allele modify this association.

Section snippets

Participants

The participants of the Cardiovascular risk factors, Aging and Incidence of Dementia (CAIDE) study were the survivors of four separate, independent, population-based random samples examined within the framework of the North Karelia Project and the FINMONICA study. These surveys assessed the cardiovascular risk factors in two eastern provinces of Finland: North Karelia and Kuopio. The study design has been described in detail elsewhere.13, 14

Having being investigated once at midlife (either in

Results

Individuals who participated in leisure-time physical activity at least twice a week at midlife (active group) were somewhat older and had shorter follow-up than those in the sedentary group (table 1). Other sociodemographic and clinical characteristics did not differ significantly between the two activity groups. The proportions of participants with dementia and AD later in life was lower in the active group.

The active group had lower odds of dementia later in life compared with the sedentary

Discussion

This study shows that leisure-time physical activity at midlife is related to a decreased risk of dementia and AD. Individuals participating at least twice a week in a leisure-time physical activity had 50% lower odds of dementia compared with sedentary persons. The association was somewhat stronger for AD than for overall dementia; those in the active group had 60% lower odds of AD compared to those in sedentary group, even after adjusting for a wide array of potential confounding factors. The

References (49)

L Fratiglioni et al.
An active and socially integrated lifestyle in late life might protect against dementia
Lancet Neurol
(2004)
GA Broe et al.
Health habits and risk of cognitive impairment and dementia in old age: a prospective study on the effects of exercise, smoking and alcohol consumption
Aust N Z J Public Health
(1998)
M Richards et al.
Does active leisure protect cognition? Evidence from a national birth cohort
Soc Sci Med
(2003)
MF Folstein et al.
“Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975)
KP Riley et al.
Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study
Neurobiol Aging
(2005)
LJ Launer
Demonstrating the case that AD is a vascular disease: epidemiologic evidence
Ageing Res Rev
(2002)
L Tong et al.
Effects of exercise on gene-expression profile in the rat hippocampus
Neurobiol Dis
(2001)
CW Cotman et al.
Exercise: a behavioural intervention to enhance brain health and plasticity
Trends Neurosci
(2002)
O Lazarov et al.
Environmental enrichment reduces Aβ levels and amyloid deposition in transgenic mice
Cell
(2005)
Physical activity and cardiovascular health
JAMA
(1996)

R Brookmeyer et al.

Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset

Am J Public Health

(1998)

J Marx

Preventing Alzheimer's: a lifelong commitment?

Science

(2005)

D Laurin et al.

Physical activity and risk of cognitive impairment and dementia in elderly persons

Arch Neurol

(2001)

J Lindsay et al.

Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging

Am J Epidemiol

(2002)

RD Abbott et al.

Walking and dementia in physically capable elderly men

JAMA

(2004)

T Yoshitake et al.

Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese Hisayama Study

Neurology

(1995)

N Scarmeas et al.

Influence of leisure activity on the incidence of Alzheimer's disease

Neurology

(2001)

J Verghese et al.

Leisure activities and the risk of dementia in the elderly

N Engl J Med

(2003)

LJ Podewills et al.

Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study

Am J Epidemiol

(2005)

E Vartiainen et al.

Twenty-years trends in coronary risk factors in North-Karelia and in other areas of Finland

Int J Epidemiol

(1994)

M Kivipelto et al.

Midlife vascular risk factors and late-life mild cognitive impairment. A population-based study

Neurology

(2001)

R-R Pate et al.

Physical activity and public health. A recommendation from the Center for Disease Control and Prevention and the American College of Sports Medicine

JAMA

(1995)

The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults

Med Sci Sports Exerc

(1998)

K Tsukamoto et al.

Determination by PCR-RFLP of ApoE genotype in a Japanese population

J Lab Clin Med

(1993)

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Fast track — ArticlesLeisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Participants

Results

Discussion

Lancet Neurol

Aust N Z J Public Health

Soc Sci Med

J Psychiatr Res

Neurobiol Aging

Ageing Res Rev

Neurobiol Dis

Trends Neurosci

Cell

Physical activity and cardiovascular health

JAMA

Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset

Am J Public Health

Preventing Alzheimer's: a lifelong commitment?

Science

Physical activity and risk of cognitive impairment and dementia in elderly persons

Arch Neurol

Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging

Am J Epidemiol

Walking and dementia in physically capable elderly men

JAMA

Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese Hisayama Study

Neurology

Influence of leisure activity on the incidence of Alzheimer's disease

Neurology

Leisure activities and the risk of dementia in the elderly

N Engl J Med

Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study

Am J Epidemiol

Twenty-years trends in coronary risk factors in North-Karelia and in other areas of Finland

Int J Epidemiol

Midlife vascular risk factors and late-life mild cognitive impairment. A population-based study

Neurology

Physical activity and public health. A recommendation from the Center for Disease Control and Prevention and the American College of Sports Medicine

JAMA

The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults

Med Sci Sports Exerc

Determination by PCR-RFLP of ApoE genotype in a Japanese population

J Lab Clin Med

Fast track — Articles
Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease