Effective diagnosis of Alzheimer's disease (AD) is of primary importance in biomedical research. Recent studies have demonstrated that neuroimaging parameters are sensitive and consistent measures of AD. In addition, genetic and demographic information have also been successfully used for detecting the onset and progression of AD. The research so far has mainly focused on studying one type of data source only. It is expected that the integration of heterogeneous data (neuroimages, demographic, and genetic measures) will improve the prediction accuracy and enhance knowledge discovery from the data, such as the detection of biomarkers. In this paper, we propose to integrate heterogeneous data for AD prediction based on a kernel method. We further extend the kernel framework for selecting features (biomarkers) from heterogeneous data sources. The proposed method is applied to a collection of MRI data from 59 normal healthy controls and 59 AD patients. The MRI data are pre-processed using tensor factorization. In this study, we treat the complementary voxel-based data and region of interest (ROI) data from MRI as two data sources, and attempt to integrate the complementary information by the proposed method. Experimental results show that the integration of multiple data sources leads to a considerable improvement in the prediction accuracy. Results also show that the proposed algorithm identifies biomarkers that play more significant roles than others in AD diagnosis. © 2008 ACM.
PMID: 19170447;PMCID: PMC2701389;Abstract:
Previously, utilizing a series of genome-wide association, brain imaging, and gene expression studies we implicated the KIBRA gene and the RhoA/ROCK pathway in hippocampal-mediated human memory. Here we show that peripheral administration of the ROCK inhibitor hydroxyfasudil improves spatial learning and working memory in the rodent model. This study supports the action of ROCK on learning and memory, suggests the potential value of ROCK inhibition for the promotion of cognition in humans, and highlights the powerful potential of unbiased genome-wide association studies to inform potential novel uses for existing pharmaceuticals. © 2009 American Psychological Association.
To identify changes in brain functions associated with the development of dementia, brain metabolism and cognition were assessed repeatedly in 12 adults with Down syndrome (DS) using positron emission tomography and neuropsychological tests. Ten subjects remained non-demented (ND) and showed no significant changes over time in cognitive measures or in cerebral metabolism. Two subjects developed dementia after 7 years. Brain functions were relatively stable prior to the onset of dementia; after the onset of dementia, both cognitive function and glucose metabolism in parietal and temporal brain regions known to be vulnerable to Alzheimer disease (AD) showed a rapid linear decline. These findings support the concept that brain functions are stable over time in ND individuals with DS and that decline of brain functions in DS subjects with dementia follows two distinct phases that correspond to the clinical progression of AD. This may have implications for timing of new therapeutic strategies.
Objective: To determine whether memory loss is detectable before the symptomatic presentation of mild cognitive impairment (MCI) in those at greater genetic risk for Alzheimer disease (AD) based upon presence or absence of the e4 allele of APOE. Methods: Participants were age 50 years or older who responded to newspaper advertisements. A total of 212 cognitively normal individuals of known APOE genotype were initially enrolled in a match paradigm that included e4 homozygotes, e3/4 heterozygotes, and e4 noncarriers in a 1:1:2 ratio (53 sets). Of the original 212 individually matched participants, 180 completed at least two epochs of testing including 45 APOE e4/4 homozygotes, 42 APOE e3/4 heterozygotes, and 93 APOE e4 noncarriers, mean age 60 (±6.2) years. Of these, four developed MCI or AD during the follow-up period and were excluded from analysis. Longitudinal neuropsychological study included two verbal (Auditory Verbal Learning Test [AVLT], Selective Reminding Test [SRT]) and two visual (Complex Figure Test [CFT], Visual Retention Test) memory tests. Results: Multiple measures on both verbal memory tests showed poorer performance over a mean interval of 33 months in e4 carriers than noncarriers: AVLT total learning, long term delayed recall; SRT free and cued recall. Among those age 50 to 59 years, AVLT long term delayed recall, SRT free and cued recall, and CFT recall declined more in APOE e4 carriers. No differences were found in the domains of language, spatial skills, or executive function. Conclusions: Memory declined in APOE e4 carriers before the symptomatic presentation of MCI in a cohort whose mean age was 60 years over a median period of 33 months. The decline began prior to age 60.