Journal Article

Changing perspectives regarding late-life dementia

Hachinski, Vladimir, Fotuhi, Majid, Whitehouse, Peter J.

2009

Overview

The view of cognitive impairment in elderly individuals has evolved over the centuries, from a normal inevitable part of aging, through demonic possession and hardening of blood vessels, to Alzheimer disease. As Fotuhi et al . discuss in this article, individuals over 80 years of age rarely have 'pure Alzheimer disease' or 'pure vascular dementia'. The authors present a new framework, known as the dynamic polygon hypothesis, which reflects the complex interplay of factors that contribute to cognitive impairment in the oldest old. Individuals over 80 years of age represent the most rapidly growing segment of the population, and late-life dementia has become a major public health concern worldwide. Development of effective preventive and treatment strategies for late-life dementia relies on a deep understanding of all the processes involved. In the centuries since the Greek philosopher Pythagoras described the inevitable loss of higher cognitive functions with advanced age, various theories regarding the potential culprits have dominated the field, ranging from demonic possession, through 'hardening of blood vessels', to Alzheimer disease (AD). Recent studies suggest that atrophy in the cortex and hippocampus—now considered to be the best determinant of cognitive decline with aging—results from a combination of AD pathology, inflammation, Lewy bodies, and vascular lesions. A specific constellation of genetic and environmental factors (including apolipoprotein E genotype, obesity, diabetes, hypertension, head trauma, systemic illnesses, and obstructive sleep apnea) contributes to late-life brain atrophy and dementia in each individual. Only a small percentage of people beyond the age of 80 years have 'pure AD' or 'pure vascular dementia'. These concepts, formulated as the dynamic polygon hypothesis, have major implications for clinical trials, as any given drug might not be ideal for all elderly people with dementia. Key Points Over the past 27 centuries, the perception of cognitive impairment with aging has changed from a normal inevitable part of aging to being mostly attributable to Alzheimer disease (AD) Alois Alzheimer was one of the first clinician–scientists to describe the importance of vascular pathology and to de-emphasize the role of amyloid plaques in brain atrophy and late-life dementia Clinicopathological studies have consistently shown that individuals over 80 years of age generally have 'mixed' pathologies (infarcts, plaques, tangles, Lewy bodies and inflammation) rather than 'pure AD' The size of the cortex and hippocampus—more than AD or any other single pathological finding—correlates with the degrees of cognitive decline and dementia in elderly individuals Appreciating the link between midlife risk factors and late-life size of the cortex and hippocampus has serious implications for disease diagnosis, patient management, and interpretation of research findings The dynamic polygon hypothesis provides a new framework for thinking about aging and dementia that departs from the linear model proposed by the amyloid cascade hypothesis

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Aging / Alzheimer Disease - complications / Alzheimer's disease / Atrophy / Atrophy - complications / Atrophy - pathology / Blood vessels / Brain / Brain - pathology / Care and treatment / Case reports / Clinical trials / Cognition Disorders - etiology / Cognition Disorders - history / Cognition Disorders - psychology / Cognitive ability / Dementia / Dementia - complications / Dementia - etiology / Dementia - history / Dementia - psychology / Environment / Etiology / History, 20th Century / History, 21st Century / Humans / Hypotheses / Medicine / Medicine & Public Health / Memory / Neurology / Pathology / Patients / Philosophers / Prevention / Public health / Renaissance period / review-article / Risk Factors / Spirit possession / Vascular Diseases - complications