The Effect of Subsyndromal Symptoms of Depression and White Matter Lesions on Disability for Individuals With Mild Cognitive Impairment.
ABSTRACT OBJECTIVE:: To assess the effect of subsyndromal symptoms of depression (SSD) on ratings of disability for individuals with mild cognitive impairment (MCI). METHODS:: Data from 405 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Participants were evaluated at baseline and at 6-month intervals over 2 years. Severity of depressive symptoms was rated utilizing the Geriatric Depression Scale. Disability was assessed utilizing the Functional Assessment Questionnaire (FAQ). Other clinical variables included white matter lesion (WML) and intracranial brain (ICV) volumes derived from magnetic resonance imaging, ratings of overall cognitive function (Alzheimer's Disease Assessment Scale, ADAS), and apolipoprotein E (ApoE) status. Demographic variables included age, education, and gender. RESULTS:: SSD individuals had a lower volume of WML and higher frequency of ApoE [Latin Small Letter Open E]4 alleles than nondepressed participants but the two groups did not differ with respect to other clinical or demographic variables. At baseline, SSD individuals were 1.77 times more likely to have poorer FAQ scores than individuals with no symptoms of depression after controlling for the effect of cognitive functioning, ICV, WML, and ApoE status. The presence of SSD at baseline was not associated with a poorer course of disability outcomes, cognitive functioning, or conversion to dementia over 24 months. CONCLUSIONS:: SSD demonstrated a significant impact on disability for MCI individuals, who are also at high risk for functional limitations related to neurodegenerative disease. Therefore, the treatment of SSD may represent a significant avenue to reduce the burden of disability in this vulnerable patient population.
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ABSTRACT: Objective: Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in frontostriatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter hyperintensities (WMHs) on magnetic resonance imaging has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction. Methods: Magnetic resonance imaging scans and clinical gait/balance data (scores from the Short Physical Performance Battery [SPPB]) were sourced from 66 subjects in the previously published LADIS trial, performed in nondisabled individuals older than age 65 years with WMHs at study entry. Data were obtained at study entry and at 3-year follow-up. Caudate nuclei and putamina were manually traced using a previously published method and volumes calculated. The relationships between volume and physical performance on the SPPB were investigated with shape analysis using the spherical harmonic shape description toolkit. Results: There was no correlation between the severity of WMHs and striatal volumes. Caudate nuclei volume correlated with performance on the SPPB at baseline but not at follow-up, with subsequent shape analysis showing left caudate changes occurred in areas corresponding to inputs of the dorsolateral prefrontal, premotor, and motor cortex. There was no correlation between putamen volumes and performance on the SPPB. Conclusion: Disruption in frontostriatal circuits may play a role in mediating poorer physical performance in individuals with WMHs. Striatal volume and shape changes may be suitable biomarkers for functional changes in this population.American Journal of Geriatric Psychiatry 01/2013; 23(1). DOI:10.1016/j.jagp.2013.04.011 · 3.52 Impact Factor
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ABSTRACT: The Genetics Core of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), formally established in 2009, aims to provide resources and facilitate research related to genetic predictors of multidimensional Alzheimer’s disease (AD)-related phenotypes. Here, we provide a systematic review of genetic studies published between 2009 and 2012 where either ADNI APOE genotype or genome-wide association study (GWAS) data were used. We review and synthesize ADNI genetic associations with disease status or quantitative disease endophenotypes including structural and functional neuroimaging, fluid biomarker assays, and cognitive performance. We also discuss the diverse analytical strategies used in these studies, including univariate and multivariate analysis, meta-analysis, pathway analysis, and interaction and network analysis. Finally, we perform pathway and network enrichment analyses of these ADNI genetic associations to highlight key mechanisms that may drive disease onset and trajectory. Major ADNI findings included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU, CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6) that were later replicated on different data sets. Several other genes (e.g., APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI phenotypes, warranting further investigation on other data sets. The broad availability and wide scope of ADNI genetic and phenotypic data has advanced our understanding of the genetic basis of AD and has nominated novel targets for future studies employing next-generation sequencing and convergent multi-omics approaches, and for clinical drug and biomarker development. Electronic supplementary material The online version of this article (doi:10.1007/s11682-013-9262-z) contains supplementary material, which is available to authorized users.Brain Imaging and Behavior 10/2013; 8(2). DOI:10.1007/s11682-013-9262-z · 4.60 Impact Factor
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ABSTRACT: The anterior cingulate cortex (ACC) is recognized as a key structure in the pathogenesis of depression. This study aimed to investigate the resting-state regional activity and functional connectivity of the ACC in a community sample of elderly individuals with subthreshold depression (StD). We employed resting-state functional magnetic resonance imaging to acquire data from 19 elderly subjects with StD and 18 normal controls. We used a regional amplitude of low-frequency fluctuation (ALFF) analysis and a correlation-based functional connectivity (FC) approach to explore changes in local activity and remote connectivity of the ACC in StD. Compared to controls, the StD group demonstrated increased ALFF in the anterior portion of the dorsal ACC (adACC). The adACC also displayed increased FC with the dorsolateral prefrontal cortex and supplementary motor area and decreased FC with several subcortical regions. The FC levels of the adACC displayed a trending correlation with self-reported depressive symptoms. This study is the first to reveal the ACC changes in resting-state activity and connectivity in the elderly with StD, suggesting that altered ALFF/FC of the adACC is an important feature of StD.Psychiatry Research : Neuroimaging 04/2014; DOI:10.1016/j.pscychresns.2014.02.013 · 2.83 Impact Factor