greater in the PSCI group (2.15 vs. 0.85; p = < 0.001) while the periventric- ular white matter hyperintensity demonstrated a trend towards significance. (2.35 vs.
S756
Poster Presentations P4
greater in the PSCI group (2.15 vs. 0.85; p ¼ < 0.001) while the periventricular white matter hyperintensity demonstrated a trend towards significance (2.35 vs. 1.39; p ¼ 0.067). Left sided deep subcortical white matter hyperintensity was associated with a 3.5 times increased risk of PSCI. Conclusions: White matter hyperintensity, specifically deep subcortical white matter hyperintensity is an important risk factor for late PSCI.
P4-148
MULTIMODALITY IMAGING DIFFERENTIATES DEMENTIA WITH LEWY BODIES FROM ALZHEIMER’S DISEASE 1
1
1
1
Kejal Kantarci* , Bradley Boeve , Val Lowe , Mathew Senjem , Stephen Weigand1, Scott Przybelski1, Gregory Preboske1, David Knopman1, Glenn Smith1, Tanis Ferman1, Ronald Petersen1, Clifford Jack1, 1Mayo Clinic, Rochester, Minnesota, United States. Background: The two most common neurodegenerative disorders associated with dementia in the elderly are Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Imaging markers that are associated with specific pathophysiological processes of AD and DLB may be complementary distinguishing these disorders. Pittsburgh Compound-B (PiB) retention on PET is a surrogate marker for b-amyloid pathology and cortical atrophy on MRI is associated with neurodegeneration and the neurofibrillary pathology of AD. Patients with DLB are characterized by occipital hypometabolism on FDG PET. Our objective was to determine whether PiB retention, cortical atrophy and decreased glucose metabolism are complementary in differentiating patients with DLB from AD. Methods: We studied age, gender and education matched patients with DLB (n ¼ 19), AD (n ¼ 19), from the Mayo Clinic Alzheimer’s Disease Research Center and cognitively normal subjects (CN) (n ¼ 38) from the Mayo Clinic Study on Aging. Subjects underwent clinical evaluation, MRI, FDG PET and PiB PET within six weeks. A global cortical PiB retention summary measure was formed by combining frontal, temporal and parietal PiB retention scaled to cerebellar retention. Cortical FDG PET uptake was scaled to pons uptake. Voxel-based analysis was performed on SPM5 to determine regional differences in cortical atrophy, PiB retention, and glucose metabolism among the clinical groups. Results: Glucose metabolism on FDG PET was significantly reduced in the parietooccipital cortex in patients with DLB compared to CN but only the occipital hypometabolism distinguished patients with DLB from AD. Global cortical PiB retention in DLB patients was significantly higher than CN but lower than AD subjects and AD patients had significantly greater atrophy in the hippocampus compared to DLB patients (p < 0.05 corrected for family-wise error for all comparisons). The area under receiver operating characteristic (AUROC) for distinguishing AD and DLB using logistic regression were 0.87 for PiB retention, 0.83 for occipital hypometabolism and 0.90 for hippocampal volumes. The AUROC increased to 0.97 when all three imaging markers were included in the model. Conclusions: Both MRI and PET contribute to characterizing distinct neurodegenerative mechanisms in AD and DLB. Hippocampal atrophy, global cortical PiB retention and occipital lobe FDG uptake were complimentary in distinguishing AD and DLB patients.
P4-149
APOE IS ASSOCIATED WITH VASCULAR DEMENTIA - USING ALZGENE-LIKE APPROACHES TO INVESTIGATE SUSCEPTIBILITY GENES FOR VASCULAR COGNITIVE IMPAIRMENT
Patrick Kehoe*1, Rebecca Dwyer1, Olivia Skrobot2, Marcus Munafo3, Patrick Kehoe3, 1Bristol University, Bristol, United Kingdom; 2Univeristy of Bristol, Bristol, United Kingdom; 3University of Bristol, Bristol, United Kingdom. Background: After Alzheimer’s disease (AD), Vascular dementia (VaD) is arguably the second most common dementia and represents a heterogeneous group of related conditions involving cognitive decline, resulting from inadequate cerebrovascular supply. Despite its prevalence, relatively few gene association studies of non-familial VaD have been conducted, partly due to the lack of universally adopted classification criteria and its often frequent co-morbidity with AD, both of which make sample collection problematic. Methods: We used Alzgene-like methods (www.Alzgene.org) to conduct the first systematic review of candidate gene association studies of VaD and its broader term vascular cognitive impairment (VCI) published up until 23rd October 2009. Fifty seven polymorphisms across 35 genes were identified. Systematic meta-analysis was used on 4 of these polymorphisms, which met the required available data from at least 4 case-control cohorts. Results: APOE e4 (rs429358) was found to be significantly associated with increased risk of VaD (OR ¼ 1.737, 95% CI 1.500-2.012, p < 0.001) with no evidence of publication bias although there were some ethnic differences. No significant associations were found for the remaining ACE, MTHFR and PSEN-1 polymorphisms that were analysed. Conclusions: While large-scale genetic association studies are awaited, this paper supports the utility of the Alzgene methodology in the identification of genetic associations amongst less common forms of dementia. P4-150
DEMENTIA IN IDIOPATHIC NORMAL PRESSURE HYDROCEPHALUS: KUOPIO NPH STUDY
Anne Koivisto*1, Irina Alafuzoff2, Sakari Savolainen3, Anna Sutela3, Jaana Rummukainen3, Ritva Vanninen1, Juha J€a€askel€ainen1, Hilkka Soininen1, Jaakko Rinne4, Ville Leinonen3, 1University of Eastern Finland, Kuopio, Finland; 2University of Eastern Finland,, Kuopio, Finland; 3Kuopio University Hospital, Kuopio, Finland; 4Kuopio University Hospitla, Kuopio, Finland. Background: Idiopathic normal pressure hydrocephalus (iNPH) causescognitive failure that can be alleviated by shunting. Long-term outcome studiesof shunted iNPH patients are scarce. Methods: We evaluated 468 patients with suspected NPH. All thepatients were examined by the neurologist and evaluated for the signs ofdementia. A Frontal cortical biopsy was taken prior to intraventricularpressure monitoring. Results: Totally 146 of the patients were diagnosed to have shunt responsive iNPH (medianfollow-up with 4.8 years). During the follow-up period, 80% of them were observedto have cognitive decline, half of them sufficient for clinical dementia. Themost common clinical diagnoses were Alzheimer’s disease and vascular dementia. Interestingly, 21% of the iNPH patients had clinically NPH-related cognitive failure, 12 % of them without any other possible comorbidity in care fuldiagnostic evaluation. Memory deficit as a leadingclinical symptom clearly generally predicted dementia in the whole study group (p < 0.001). On the contrary, in demented iNPHpatients without any other neurodegenerative comorbidity, gait disturbances had been the firstand leading symptom followed by the later deterioration of cognition. Conclusions: The iNPH patients are in high risk of progressivecognitive decline despite of primary shunt-response. A proportion of them suffers clinically distinctNPH-related dementia which may be a potential independent cause of progressivecognitive decline. Furthermore, our data demonstrates that iNPH patients haveoften other concurrent degenerative brain disease. P4-151
RESEARCH CONSORTIUM OF AMYOTROPHIC LATERAL SCLEROSIS/PARKINSONISMDEMENTIA COMPLEX OF THE KII PENINSULA OF JAPAN
Yasumasa Kokubo*1, Shigeo Murayama2, Hiroyuki Tomiyama3, Yoshihumi Hirokawa4, Masatho Hasegawa5, Kazushi Okamoto6,
