T402
Poster Presentations P2:
Results: Compared with the baseline, a significant cluster of increased FA located in the right parietal lobe (Figure 1) was observed while the score of MMSE remained unchanged. There were no areas of significantly decreased FA, increase MD or decreased MD observed in AD patients compared with controls. Conclusions: Our preliminary result showed changes of brain diffusivity can be detected prior to the significant change of clinical manifestations. In agreement with previous studies, we found the involvement of white matter in parietal lobe which may be one the first brain regions in response to the treatment. We conclude that Donepezil treatment bring new changes in brain structures of AD patients, and DTI (especially FA) may be used to monitor the early therapeutic effect.
replication cohort of Dutch FTLD cases (N⫽230), and controls (N⫽484) were also genotyped for these tagging SNPs. 3 of the UBAP1 SNPs associated with FTLD in the Dutch data, with a maximum haplotype association of OR 1.39 (95% CI 1.02-1.89, P⫽ 0.033). Combined analysis resulted in a haplotype association of P⫽0.014, with a maximum haplotype risk of OR 1.42 (95% CI 1.12-1.80, P⫽0.003). Conclusions: These data suggest that UBAP1 is a risk factor for FTLD in at least two different populations. Analysis of UBAP1 in chr9p-linked families is required. Molecular and biochemical characterisation of UBAP1 is underway to determine the biological basis of this association. P2-107
ANXIETY AND APATHY ARE ASSOCIATED WITH PROBABLE REM SLEEP BEHAVIOR DISORDER AMONG COGNITIVELY NORMAL ELDERLY SUBJECTS: THE MAYO CLINIC STUDY OF AGING
Jennifer Molano, Bradley Boeve, Rosebud Roberts, Yonas V. Geda, David Knopman, Eric Tangalos, Glenn Smith, Robert Ivnik, Ruth Cha, Vernon Pankratz, Michael Silber, Tanis Ferman, Ronald Petersen, Mayo Clinic, Rochester, MN, USA. Contact e-mail:
[email protected]
P2-106
UBAP1 IS A RISK FACTOR FOR FRONTOTEMPORAL LOBAR DEGENERATION
Sara J. Rollinson1, Stephen K. Sikkink1, Nicola A. Halliwell1, Patrizia Rizzu Rizzu2, Peter Heutink2, John Van Swieten3, David Mann4, Stuart Pickering-Brown1, 1University of Manchester, Manchester, United Kingdom; 2Section Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, Netherlands; 3Erasmus MC, Rotterdam, P.O. Box 2040, Rotterdame, Netherlands; 4Greater Manchester Neurosciences Centre, Hope Hospital, Salford Royal Hospitals NHS Foundation Trust, Salford, United Kingdom. Contact e-mail:
[email protected] Background: Frontotemporal lobar degeneration (FTLD) is a heterogeneous neurodegenerative syndrome that includes the clinical syndromes of frontotemporal dementia, semantic dementia, progressive nonfluent aphasia, and progressive apraxia. Approximately 30 - 50% of cases are thought to be familial in origin. Mutations in MAPT and PGRN account for up to 20% of familial FTLD, and rare forms result from mutations of CHMP2B. Recently, linkage to chr9p was reported in families with FTLD and motor neuron disease. Methods: Based on published linkage data the chr9p minimal candidate region was defined from D9S2154 to D9S1874. Using a gene-centric approach we genotyped 190 haplotype tagging SNP’s covering this region in the Manchester FTLD cohort (N⫽214) and 286 normal controls using the Sequenom MassArray genotyping technology. Results: Using a case-control approach and sliding window haplotype analysis, UBAP1 (Ubiquitin associated protein 1) was found to be associated with a maximum sliding window P value of 0.00025. A further 12 tagging SNPs covering UBAP1 were genotyped for validation. Of the 10 SNPs that make up the haplotype block covering UBAP1, 7 were associated with FTLD with a P value of ⱕ0.05, the haplotype block itself associated with disease status with a global P value of 0.008, a finding that translates to maximum increased risk for FTLD of OR 1.71 (95% CI 1.20-2.44, P⫽0.003). A
Background: The Braak staging scheme for Parkinson’s disease posits an ascending progression of Lewy body pathology occurring in the brainstem prior to involvement of the telencephalon. One could therefore hypothesize that those with evolving Lewy body disease (LBD) would have significant pathology in the structures that are exhibited clinically by the presence of depression (DEP), anxiety (ANX), or apathy (AP) (eg, raphe nucleus, locus coeruleus, pedunculopontine/laterodorsal tegmental nuclei, and likely others) as well as those involved in REM sleep behavior disorder (RBD) pathophysiology (eg, pontomedullary circuits). We sought to explore this hypothesis by analyzing the frequencies of DEP, ANX, or AP among those with probable RBD (pRBD) in cognitively normal subjects in a populationbased study. Methods: Participants are 70-89 year old residents of Olmsted County, Minnesota. Features were viewed present based on cut-off scores: DEP-score ⬎0 on the DEP scale of the Neuropsychiatric Inventory-Questionnaire (NPI-Q) or ⱖ13 on the Beck DEP Inventory; ANX-score ⬎0 on the ANX scale of the NPI-Q or ⱖ10 on the Beck ANX Inventory; and AP-score ⬎0 on the AP scale of the NPI-Q. pRBD was considered present based on the Mayo Sleep Questionnaire-a validated screening measure for RBD. Data were analyzed on those who completed the key measures and were considered cognitively normal. Results: Among 765 subjects, the frequency of pRBD was 8.0%. The frequencies for each feature for those with and without pRBD were: DEP 16.4% vs. 13.4% (p⫽0.51); ANX 21.3% vs. 8.4% (p⬍0.01); and AP 11.5% vs. 4.3% (p⫽0.01). There were significant associations of pRBD with ANX (OR ⫽ 3.09; 95% CI ⫽ 1.56, 6.15; p⬍0.01) and AP (OR ⫽ 2.91; 95% CI ⫽ 1.21, 6.98; p⫽0.02), and no association with DEP (OR 1.27; 95% CI ⫽ 0.62, 2.60; p⫽0.52), after adjustment for age and education (as continuous variables) and sex. Conclusions: The association of ANX and AP with pRBD suggests that they may be etiologically related. Whether this association reflects LB disease affecting key brainstem nuclei will require further study. P2-108
LOWER SCORES IN ATTENTION/EXECUTIVE FUNCTIONING ARE ASSOCIATED WITH PROBABLE REM SLEEP BEHAVIOR DISORDER AMONG COGNITIVELY NORMAL ELDERLY SUBJECTS: THE MAYO CLINIC STUDY OF AGING
Jennifer Molano, Bradley Boeve, Rosebud Roberts, Glenn E. Smith, Robert Ivnik, Tanis Ferman, Yonas E. Geda, David S. Knopman, Eric G. Tangalos, Cha Ruth, V. Shane Pankratz, Michael H. Silber, Ronald Petersen, Mayo Clinic, Rochester, MN, USA. Contact e-mail:
[email protected] Background: REM sleep behavior disorder (RBD) is often associated with Lewy body disease (LBD). Neuropsychological studies in patients with
