Arbitrary associative memory: a candidate cognitive endophenotype for probable Alzheimer's disease
type: CreativeWork
description: The genetic basis of sporadic, senile onset Alzheimer’s disease (AD) is not as well documented as familial, younger-onset AD. At present, there is no evidence to support monogenic inheritance in senile onset AD or “probable AD”. As far as genetic risk factors are concerned, the apolipoprotein E epsilon-4 allele is the only reliable genetic susceptibility factor for probable AD. The investigation of cognitive endophenotypes for probable AD, or cognitive markers of liability to the condition that are theoretically closer to its genetic mechanisms than its clinical phenotype, might assist in the identification of susceptibility genes for AD. This is especially the case if these cognitive differences reflect genetically predetermined differences in brain structure and function. The traditional view of probable AD is that cognitive dysfunction emerges many years, and possibly decades, after underlying brain neuropathological, metabolic, and structural changes have begun. According to this theory, while brain functional and structural changes might be present in middle age in people at risk of developing the disease, cognitive abnormalities emerge only when a “threshold” of neurodegeneration has been reached and unaffected brain regions can no longer compensate functionally for affected areas. An alternative viewpoint is that cognitive deficits are present in the earliest stages of probable AD, but that two issues have limited our ability to detect such changes: First, previous studies have utilised tests which are not sensitive to the earliest neurocognitive changes in the condition. Second, the heterogeneous clinical phenotype of probable AD has meant that the conventional approach of comparing mean scores on cognitive tests between low-risk and high-risk groups might be masking subsets of affected people within high-risk groups. The use of more sensitive tests, in conjunction with cognitive discrepancy analyses, which compare performances within high-risk groups on com…
abstract: The genetic basis of sporadic, senile onset Alzheimer’s disease (AD) is not as well documented as familial, younger-onset AD. At present, there is no evidence to support monogenic inheritance in senile onset AD or “probable AD”. As far as genetic risk factors are concerned, the apolipoprotein E epsilon-4 allele is the only reliable genetic susceptibility factor for probable AD. The investigation of cognitive endophenotypes for probable AD, or cognitive markers of liability to the condition that are theoretically closer to its genetic mechanisms than its clinical phenotype, might assist in the identification of susceptibility genes for AD. This is especially the case if these cognitive differences reflect genetically predetermined differences in brain structure and function. The traditional view of probable AD is that cognitive dysfunction emerges many years, and possibly decades, after underlying brain neuropathological, metabolic, and structural changes have begun. According to this theory, while brain functional and structural changes might be present in middle age in people at risk of developing the disease, cognitive abnormalities emerge only when a “threshold” of neurodegeneration has been reached and unaffected brain regions can no longer compensate functionally for affected areas. An alternative viewpoint is that cognitive deficits are present in the earliest stages of probable AD, but that two issues have limited our ability to detect such changes: First, previous studies have utilised tests which are not sensitive to the earliest neurocognitive changes in the condition. Second, the heterogeneous clinical phenotype of probable AD has meant that the conventional approach of comparing mean scores on cognitive tests between low-risk and high-risk groups might be masking subsets of affected people within high-risk groups. The use of more sensitive tests, in conjunction with cognitive discrepancy analyses, which compare performances within high-risk groups on com…
author: Werden, Emile
keywords: arbitrary associative memory, Alzheimer's disease, cognition, parental history, endophenotype
date published: 2015
date modified: 2026-07-27T20:18:41Z
provider: University of Melbourne
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Melbourne

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property ID: Handle
value: http://hdl.handle.net/11343/112366