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Hippocampal Neuronal Atrophy and Cognitive Function in Delayed Poststroke and Aging-Related Dementias

Lookup NU author(s): Lizzie Gemmell, Dr Helen Bosomworth, Dr Louise Allan, Roslyn Hall, Dr Ahmad Khundakar, Arthur Oakley, Dr Vincent Deramecourt, Dr Tuomo Polvikoski, Professor John O'Brien, Professor Raj KalariaORCiD

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Abstract

BACKGROUND AND PURPOSE: We have previously shown delayed poststroke dementia in elderly (≥75 years old) stroke survivors is associated with medial temporal lobe atrophy; however, the basis of the structural and functional changes is unknown. METHODS: Using 3-dimensional stereological methods, we quantified hippocampal pyramidal neuronal volumes and densities in a total of 95 postmortem samples from demented and nondemented poststroke survivors within our prospective Cognitive Function after Stroke study and subjects pathologically diagnosed with vascular dementia, Alzheimer disease, and mixed Alzheimer disease and vascular dementia syndrome. RESULTS: Hippocampal CA1 but not CA2 subfield neuron density was affected in poststroke, Alzheimer disease, vascular dementia, and mixed dementia groups relative to control subjects (P<0.05). Neuronal volume was reduced in the poststroke dementia relative to poststroke nondemented group in both CA1 and CA2, although there were no apparent differences in neuronal density. Poststroke nondemented neuronal volumes were similar to control subjects but greater than in all dementias (P<0.05). Neuronal volumes positively correlated with global cognitive function and memory function in both CA1 and CA2 in poststroke subjects (P<0.01). Degrees of neuronal atrophy and loss were similar in the poststroke dementia and vascular dementia groups. However, in the entorhinal cortex layer V, neuronal volumes were only impaired in the mixed and Alzheimer disease groups (P<0.05). CONCLUSIONS: Our results suggest hippocampal neuronal atrophy is an important substrate for dementia in both cerebrovascular and neurodegenerative disease.


Publication metadata

Author(s): Gemmell E, Bosomworth H, Allan L, Hall R, Khundakar A, Oakley AE, Deramecourt V, Polvikoski TM, O'Brien JT, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Stroke

Year: 2012

Volume: 43

Issue: 3

Pages: 808-814

Print publication date: 29/12/2011

ISSN (print): 0039-2499

ISSN (electronic): 1524-4628

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1161/STROKEAHA.111.636498

DOI: 10.1161/STROKEAHA.111.636498

PubMed id: 22207507


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Funding

Funder referenceFunder name
Alzheimer's Research United Kingdom (ARUK)
Newcastle Centre for Brain Ageing and Vitality
Newcastle National Institute of Health Research Biomedical Research Centre
Research Councils United Kingdom
Alzheimer's Society
G0400074Medical Research Council (MRC) of the United Kingdom
G0500247Medical Research Council (MRC) of the United Kingdom

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