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IC‐P‐036: Preliminary analysis of copy number variation in the ADNI cohort
Author(s) -
Swaminathan Shanker,
Kim Sungeun,
Shen Li,
Risacher Shan L.,
Foroud Tatiana,
Pankratz Nathan,
Potkin Steven G.,
Huentelman Matthew J.,
Craig David W.,
Weiner Michael W.,
Saykin Andrew J.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.050
Subject(s) - copy number variation , autism , genetics , gene duplication , gene dosage , gene , biology , medicine , genome , psychiatry , gene expression
Background: Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is associated with behavioural disturbances in approximately 50% of AD patients. Memantine is a specific, moderate affinity, noncompetitive NMDA receptor antagonist. Data from randomised, double-blind, place-controlled clinical investigations suggest memantine has a beneficial effect on behavioural symptoms of patients with moderate to severe AD, with the most pronounced effect on agitation/aggression. Compromised white matter integrity has been reported in AD. This study aimed to investigate the preliminary effect of memantine on agitation in AD patients, and additionally to explore the effect of memantine medication on white matter integrioty in AD. Methods: Twenty-six AD (NINCDS-ADRDA criteria) patients with agitation were enrolled in this study. Neuropsychiatric symptoms were evaluated with Neuropsychiatric Inventory (NPI) at baseline, week 4, 8, and 12 after memantine medication. White matter integrity was represented with values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measured on diffusion-tensor images (DTI) acquired at baseline and week 12 after memantine medication. Fifteen subjects (4 males, 11 females) completed both preand post-medication NPI evaluation and DTI imaging. The FA and ADC values were measured at the ROIs of the white matter of temporal, frontal, parietal, parahippocampal gyrus (PHG), anterior (ACG) and posterior cingulate gyrus (PCG), and genu and splenium of corpus callosum. Results: After 12-week treatment, the total score of NPI improved significantly (t1⁄4 4.208, df1⁄4 14, P1⁄4 0.001). There was significant improvement in the item scores of delusion (t 1⁄4 5.401, df 1⁄4 14, P 1⁄4 0.000) and irritability (t 1⁄4 3.581, df 1⁄4 14, P 1⁄4 0.003). After 12-week treatment of memantine, the FA and ADC values of all selected areas did not change significantly (P > 0.05). Stepwise linear regression analysis showed that the change percentage of FA values of white matter of parietal, PHG and ACG, and the ADC value of ACG would predict the change percentage of delusion item score (adjusted R 1⁄4 0.695, F 1⁄4 8.964, P 1⁄4 0.002) (Table 1). Conclusions: Memantine could improve the behavioral symptoms in AD, and maintain the white matter integrity during 12-week treatment. The change of white matter integrity in parietal, parahippocampal gyrus, and anterior cingulate gyrus measured on DTI images may be assotiated with the change of behavioral symptoms. Further large-scale long-term investigations are warranted.