Cognitive phenotypes in Alzheimer's Disease and genetic risk

Snowden, Julie S., Stopford, Cheryl L., Julien, Camille L., Thompson, Jennifer C., Davidson, Yvonne, Gibbons, Linda, Pritchard, Antonia, Lendon, Corinne L., Richardson, Anna M., Varma, Anoop, Neary, David and Mann, David M. A. (2007) Cognitive phenotypes in Alzheimer's Disease and genetic risk. Cortex, 43 7: 835-845. doi:10.1016/S0010-9452(08)70683-X

Author Snowden, Julie S.
Stopford, Cheryl L.
Julien, Camille L.
Thompson, Jennifer C.
Davidson, Yvonne
Gibbons, Linda
Pritchard, Antonia
Lendon, Corinne L.
Richardson, Anna M.
Varma, Anoop
Neary, David
Mann, David M. A.
Title Cognitive phenotypes in Alzheimer's Disease and genetic risk
Journal name Cortex   Check publisher's open access policy
ISSN 0010-9452
Publication date 2007
Sub-type Article (original research)
DOI 10.1016/S0010-9452(08)70683-X
Volume 43
Issue 7
Start page 835
End page 845
Total pages 11
Place of publication Milano, Italy
Publisher Elsevier Masson
Language eng
Subject 1109 Neurosciences
Abstract Variation in the clinical characteristics of patients with Alzheimer's disease (AD) is increasingly recognised, although the factors underlying variation are not fully understood. The study examined the cognitive characteristics of 523 AD patients at the time of their presentation to a neurological dementia clinic and explored the relationship to family history and apolipoprotein E (APOE) genotype. Distinct profiles were identified, which were mirrored by topographical differences on neuroimaging. Clinical distinctions were maintained over time. Two-thirds of patients showed a constellation of deficits at presentation which included memory, language, visuospatial and constructional difficulties. However, a quarter had circumscribed presentations of amnesia, aphasia, perceptuospatial disorder or apraxia. The rare presence of frontal lobe characteristics was associated with a younger age of onset, an increased incidence of myoclonus at presentation, a positive family history but not with possession of APOE ɛ4 allele. An amnestic presentation (severe, yet circumscribed amnesia) was strongly associated with an older age of onset, a positive family history and the presence of APOE ɛ4 allele. Posterior cortical presentations showed a female bias, were typically sporadic, and showed no association with APOE ɛ4. The findings support the notion of phenotypic variation in AD, and show that genetic risk factors can influence clinical presentation. The findings draw attention to the specific association between APOE ɛ4 allele and memory but challenge the commonly held notion that the presence of the ɛ4 allele inevitably reduces onset age. The findings indicate that risk factors other than APOE ɛ4 allele underlie the non-familial, early onset posterior hemisphere presentations of AD.
Keyword Alzheimer's disease
APOE [.epsilon]4
Cognitive impairment
Genetic risk
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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