The Effect of Subsyndromal Symptoms of Depression and White Matter Lesions on Disability for Individuals With Mild Cognitive Impairment

ArticleinThe American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 21(9) · September 2012with9 Reads
DOI: 10.1097/JGP.0b013e318263a0b6 · Source: PubMed
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 ε4 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.
    • "The ε2 allele was associated with slower changes in daily functioning over time and better neuropsychological performance across a number of measures, demonstrating the expected protective effect of APOE ε2 allele. In addition, the relationship between subsyndromal symptoms of depression (SSD) in MCI patients and APOE ε4 allele carrier status was investigated with a higher frequency of ε4 allele carriers found in participants with SSD (Mackin et al. 2012). While many studies investigated a targeted set of SNPs, other studies have performed GWAS of cognitive decline of patients with MCI (Hu et al. 2011b), of age-at-onset of AD (Kamboh et al. 2011), of global cognitive decline in several studies with mixed diagnoses (De Jager et al. 2012 ), of executive functioning resilience (Mukherjee et al. 2012a), and of a composite measure of memory performance (Ramanan et al. 2012a). "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Oct 2013
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    Full-text · Article · Jan 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Objective To examine neuroanatomical changes associated with depressive symptoms in Alzheimer's disease (AD) and the relationship between brain structure and cerebrospinal fluid (CSF) AD biomarkers in depressed and non-depressed patients. Methods Two independent cohorts were used in this study. The first cohort (KI) was collected from the Memory Clinic at Karolinska University Hospital and consisted of 41 AD patients. The second cohort was selected and downloaded from the Alzheimer’s Disease Neuroimaging Initiative database (ADNI) and consisted of 148 patient. Patients underwent medical, neuropsychological assessment, laboratory analyses of CSF, including β amyloid 1–42 (Aβ 42), total τ (t-τ), phosphorylated τ 181 (p-τ) and brain MRI examination. In the KI cohort, depression was assessed using the Cornell Scale for Depression in Dementia, and in the ADNI cohort the Geriatric Depression Scale was applied. 3D T1-weighted MRI images were processed using automated steps for segmentation and surface reconstruction implemented in Freesurfer. General linear model analysis was used as a statistical approach. Results Cortical thinning in AD patients with depressive symptoms compared with those without was observed in the left parietal and temporal brain regions in both cohorts. Negative correlation between cortical thickness and t-τ was greater in depressed compared with non-depressed AD patients in precuneus and parahippocampal cortex. Conclusions Our findings suggest that depressive symptoms in AD patients are associated with cortical thinning in temporal and parietal regions. In addition, our findings suggest that τ protein pathology in these areas may contribute to the development of depressive symptoms in AD.
    Article · Jan 2014
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