The epidemiologic study of dementia: a life-long quest?

doi:10.1016/j.neurobiolaging.2004.03.016

Neurobiology of Aging

Volume 26, Issue 3, March 2005, Pages 335-340

https://doi.org/10.1016/j.neurobiolaging.2004.03.016 Get rights and content

Abstract

Based on many experimental and observational studies we now understand that neurodegenerative brain changes begin by middle age. Characteristics of the risk factors for these brain changes may also change with age. A review is conducted of studies that report on the association of mid-life risk factors to late cognitive impairment and dementia. Issues related to the interpretation of the data are discussed. The studies suggest that mid-life cardiovascular risk factors, and in particular elevated levels of blood pressure, increase the risk for late-life cognitive impairment and dementia. Our understanding the contribution of cardiovascular risk factors to late age brain disease has been helped tremendously by prospective studies with long follow-up. To better understand which risk factors lead to disease initiation, progression and prognosis, a life course approach to the epidemiologic study of dementia is needed.

Section snippets

Brain structure and function

Studies conducted at different ages suggest brain aging begins relatively early. From the studies of Braak et al. [2], we have learned that the classical markers of Alzheimer's disease pathology can start to appear in autopsied brains of 40-year-olds. White matter hyperintensities appear on magnetic resonance images (MRI) of the brains of middle-age adults without a history of cerebrovascular disease [24]. Cross-sectional MRI studies show that selected sub-regions of the hippocampus also begin

Risk factors

The levels of risk factors, such as a blood pressure or cholesterol level, also change with age, as a result of alterations in brain and peripheral structures, in gene expression, and in the nature of endogeneous and exogenous environmental exposures.

Long-term perspectives on the study of dementia: mid-life risk factors and the risk for late-life disorders of cognition

These age-related changes in brain structure and function, and concurrent changes in risk factors for cognitive impairment may be dependent or independent and various scientific approaches are needed to determine how such changes are related. One important approach is prospective population-based studies that measure cognitive function in late age—and risk factors in early and middle age, when presumably risk factors are less affected by the disease. The value of prospective studies of dementia

Lessons about diseases of cognition from the long-term follow-up studies

The body of research reviewed here suggests mid-life levels of cardiovascular risk factors, and in particular elevated levels of blood pressure, increase the risk for DOC that emerge 20 years or more after the risk factor is measured. There is some support for the hypothesis that increased genetic susceptibility, marked by having the apolipoprotein E ɛ4 allele, may interact with these risk factors to increase the risk for DOC. Chronic inflammation may also contribute to an increased risk for

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The epidemiologic study of dementia: a life-long quest?

Abstract

Section snippets

Brain structure and function

Risk factors

Long-term perspectives on the study of dementia: mid-life risk factors and the risk for late-life disorders of cognition

Lessons about diseases of cognition from the long-term follow-up studies

Ann Epidemiol

Prog Brain Res

Endocrinol Metab Clin N Am

Lancet

Endocrinol Metab Clin N Am

Neurobiol Aging

J Psychosom Res

Lancet

Neurobiol Aging

Am J Cardiol

Lancet

Prev Med

Neurobiol Aging

Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins

Neurology

Midlife cardiovascular risk factors and brain morphology in identical older male twins

Neurology

Pulmonary function measures as predictors and correlates of cognitive functioning in later life

Am J Epidemiol

Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute twin study

Arch Neurol

A follow-up study of blood pressure and cerebral white matter lesions

Ann Neurol

Aortic atherosclerosis at middle age predicts cerebral white matter lesions in the elderly

Stroke

Untreated blood pressure level is inversely related to cognitive functioning: the Framingham study

Am J Epidemiol

Lipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group

Circulation

Blood pressure and cognitive performance. The Framingham study

Am J Epidemiol

Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates

Eur J Endocrinol

Smoking history in middle age and subsequent cognitive performance in elderly Japanese-American men. The Honolulu-Asia aging study

Am J Epidemiol

Embracing complexity: a consideration of hypertension in the very old

J Gerontol A Biol Sci Med Sci

Low blood pressure and dementia in elderly people: the Kungsholmen project

BMJ

Variability in midlife systolic blood pressure is related to late-life brain white matter lesions: the Honolulu-Asia aging study

Stroke