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Introduction Molecular imaging has been developed and validated in Thai patients, comprising a portion of patients in the dementia registry. This should provide a more accurate diagnosis of the etiology of dementia, which was the focus of this study. Methods This was a multicenter dementia study. The baseline characteristics, main presenting symptoms, and results of investigations and cognitive tests of the patients were electronically collected in the registry. Functional imaging and/or molecular imaging were performed in patients with an equivocal diagnosis of the causes of dementia, especially in atypical dementia or young onset dementia (YOD). Results There were 454 patients in the study. The mean age of the patients was 78 years, with 60% female. Functional imaging and/or molecular imaging were performed in 57 patients (57/454 patients, 13%). The most common cause of dementia was Alzheimer's disease (AD; 50%), followed by vascular dementia (VAD; 24%), dementia with Lewy bodies (6%), Parkinson's disease dementia (6%), frontotemporal dementia (FTD; 2.6%), progressive supranuclear palsy (2%), multiple system atrophy (0.8%), and corticobasal syndrome (0.4%). YOD accounted for 17% (77/454 patients), with a mean age of 58 years. The causes of YOD were early onset amnestic AD (44%), VAD (16%), behavioral variant FTD (8%), posterior cortical atrophy (6.5%), and logopenic variant primary progressive aphasia (5.2%). Conclusion AD was the most common cause of dementia in Thai patients and the distribution of other types of dementia and main presenting symptoms were similar to previous reports in Western patients; however, the proportion of YOD was higher.

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.

Background: Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. Methods: We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD+). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. Results: Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values >.05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD+ compared with SCD− (all false discovery rate–adjusted p values −, SCD+ subjects showed increased pDMN–MTMS connectivity (false discovery rate–adjusted p

Donepezil is the first cholinesterase inhibitor widely used for the treatment of Alzheimer's disease (AD). Its pharmacological actions are straightforward, enhancing cholinergic activity both in the brain and systemically, with a long-enough half-life to allow for once a day dosing. Its efficacy has been approved for use in mild-to-moderate AD stage for improvement of symptoms for 10 years, and now it is also approved for use in severe stage.This review article will offer a 10-year perspective on the use of donepezil in clinical practice against AD and related disorders. In addition to discussing the information from randomized clinical trials and from the drug monograph, this article will seek to facilitate the clinical development and clinical use of the next generation of drugs for AD.Adjustments about expectations and safe use of donepezil were made over time based on such clinical experiences. Offering a cholinesterase inhibitor to patients with mild-to-moderate AD clearly showed advantages. If well tolerated, donepezil should be continued in the severe stages of AD as long as the patient appears to benefit from a slower clinical decline.

Lucas Porcello Schilling, Eduardo Rigon Zimmer, Antoine Leuzy, Andrea Lessa Benedet, Tharick Pascoal, Sara Mohades, Sulantha Mathotaarachch, Laksanun Cheewakriengkrai, Monica Shin, Maxime Parent, Min Su Kang, Sarinporn Manitsirikul, Daliah Farajat, Seqian Wang, Jessica Di Ciero, Thomas Beaudry, Simon Eskildsen, Jared Rowley, Felix Carbonell, Vladmir Fonov, Serge Gauthier, Pedro Rosa-Neto, McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; PUCRS, Porto Alegre, Quebec, Brazil; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; Aarhus University, Aarhus, Denmark. Canada; Biospective Inc., Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada. Contact e-mail: lucaspschilling@gmail.com

IC-P-194 REGIONAL ASSOCIATION MAPS DESCRIBE DYNAMIC ARCHITECTURE OFAMYLOIDOSIS AND HYPOMETABOLISM IN ALZHEIMER’S DISEASE Sulantha Sanjeewa Mathotaarachchi, Sara Mohades, Eduardo Rigon Zimmer, Felix Carbonell, Thomas Beaudry, Maxime Parent, Andrea Lessa Benedet, Seqian Wang, Monica Shin, Vladimir S. Fonov, Laksanun Cheewakriengkrai, Antoine Leuzy, Lucas Porcello Schilling, Sarinporn Manitsirikul, Simon Eskildsen, Min Su Kang, Serge Gauthier, Pedro Rosa-Neto, McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Center-McGill Centre for Studies in Aging, Montreal, Quebec, Canada; McGill Center for Studies in Aging, Montreal, Quebec, Canada; Biospective Inc., Montreal, Quebec, Canada; McGill Centre for Studies in Aging, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill Centre for Studies in Aging/Translational Neuroimaging Laboratory, Montreal, Quebec, Canada; McGill University, Porto Alegre, Brazil. Contact e-mail: sulantha.s@gmail.com

old. Three hundred fourteen (314) subjects have multiple MRIs, 52 have NP data , and 268 have genotype data at ADGC. After restricting to UDS visits within 180 days of a MRI (n1⁄41379), corresponding cognitive diagnoses consisted of 830 (60.2%) normal cognition, 308 (22.3%) mild cognitive impairment, and 241 (17.5%) dementia, among which 222 (92.1%) were primary probable or possible AD. Associated data from standardized assessments of behavioral and motor symptoms, functional activities, neurologic exam, and neuropsychological tests are also available. Conclusions: The NACC MRI Database is a large, freely available sample of MRIs that are linked to the rich, standardized UDS and NP data, as well as genotype data from ADGC.

The purpose of this project was to evaluate white matter degeneration and its impact on hippocampal structural connectivity in patients with amnestic mild cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer’s disease. We estimated white matter fractional anisotropy, mean diffusivity and hippocampal structural connectivity in two independent cohorts. The ADNI cohort included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer’s disease]. A second cohort included 34 subjects [15 cognitively normal and 19 amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent clinical and neuropsychological assessment in addition to diffusion and T1 MRI. Individual fractional anisotropy and mean diffusivity maps were generated using FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the probability of connectivity between the hippocampus and cortex were generated using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics of fractional anisotropy, mean diffusivity and hippocampal structural connectivity were estimated using Tract-Based Spatial Statistics. The proportion of abnormal to total white matter volume was estimated using the total volume of the white matter skeleton. We found that in both cohorts, amnestic mild cognitive impairment patients had 27-29% white matter volume showing higher mean diffusivity but no significant fractional anisotropy abnormalities. No fractional anisotropy or mean diffusivity differences were observed between non-amnestic mild cognitive impairment patients and cognitively normal subjects. Alzheimer’s disease patients had 66.3% of normalized white matter volume with increased mean diffusivity and 54.3% of the white matter had reduced fractional anisotropy. Reduced structural connectivity was found in the hippocampal connections to temporal, inferior parietal, posterior cingulate and frontal regions only in the Alzheimer’s group. The severity of white matter degeneration appears to be higher in advanced clinical stages, supporting the construct that these abnormalities are part of the pathophysiological processes of Alzheimer’s disease.