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4 and the pattern of regional brain atrophy in Alzheimer’s disease
From the Departments of Clinical Neurosciences (Drs. Hashimoto, Tanimukai, Hirono, Kazui, and Mori), Basic Neurosciences (Dr. Yasuda), and Neuroimaging Research (Dr. Matsui), Hyogo Institute for Aging Brain and Cognitive Disorders, Himeji, Japan.
Address correspondence and reprint requests to Dr. M. Hashimoto, Clinical Neurosciences, Hyogo Institute for Aging Brain and Cognitive Disorders, 520 Saisho-Ko, Himeji, 670-0981, Japan; e-mail: hashi-m{at}hiabcd.go.jp
Background: — Although the APOE 
4 allele increases the risk of developing AD, the effects of the 4 allele on brain atrophy in clinical AD patients are controversial.
Objective: — To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD.
Methods: — Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the 3/3 allele, one group (n = 46) had the 3/4 allele, and one group (n = 46) had the 4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE 4 allele was also examined.
Results: — The normalized hippocampal volume was correlated with the number of APOE 4 alleles (r = -0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE 4 alleles (r = -0.178, p = 0.037). The number of APOE 4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale–Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale–Revised attention/concentration score (r = 0.191, p = 0.025).
Conclusions: — Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE 4 allele on the brains of AD patients may have regional specificity.
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