TY - JOUR
T1 - Changing perspectives regarding late-life dementia
AU - Fotuhi, Majid
AU - Hachinski, Vladimir
AU - Whitehouse, Peter J.
N1 - Funding Information:
v. Hachinski is funded by the Alzheimer Association, Award Number IIRG-08-91792. P. J. Whitehouse received support from the National Institute on Aging, Shigeo and Megumi Takayama, and the Greenwall Foundation. Barbara Crain, Miia Kivipelto and Michael Williams made significant suggestions, and we very much appreciate their critical and thoughtful comments. We thank Tzipora Sofare, Medical Editor at the Sandra and Malcolm Berman Brain & Spine Institute, for her help with the preparation of the tables and figures.
PY - 2009/12
Y1 - 2009/12
N2 - 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 hippocampusnow considered to be the best determinant of cognitive decline with agingresults 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.
AB - 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 hippocampusnow considered to be the best determinant of cognitive decline with agingresults 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.
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U2 - 10.1038/nrneurol.2009.175
DO - 10.1038/nrneurol.2009.175
M3 - Review article
C2 - 19918254
AN - SCOPUS:75049084559
SN - 1759-4758
VL - 5
SP - 649
EP - 658
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
IS - 12
ER -