Mental Illness Research and Education Clinical Center

Seattle, WA, United States

Mental Illness Research and Education Clinical Center

Seattle, WA, United States
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Li G.,University of Washington | Wang L.Y.,University of Washington | Wang L.Y.,Mental Illness Research and Education Clinical Center | Shofer J.B.,University of Washington | And 8 more authors.
Archives of General Psychiatry | Year: 2011

Context: Late-life depression is associated with increased risk of dementia, but the temporal relationship between depression and development of dementia remains unclear. Objectives: To examine the association between risk of dementia and baseline depressive symptoms; history of depression, particularly early-life (<50 years) vs latelife depression (≥50 years); and individual domains of the Center for Epidemiologic Studies Depression Scale. Design: A large cohort with initially nondemented participants was followed up biennially for up to 15 years. Baseline depressive symptoms were assessed using the 11- item version of the Center for Epidemiologic Studies Depression Scale; presence of significant depressive symptoms was defined as a score of 11 or greater. Self-reported history of depression was collected at the baseline interview. Cox proportional hazards regression was used to assess the association between depression and dementia risk. Setting: Population-based cohort drawn from members of the Group Health Cooperative in Seattle, Washington. Participants: A cohort of 3410 participants without dementia aged at least 65 years. Results: During a mean of 7.1 years of follow-up, 658 participants (19.3%) developed dementia. At baseline, 9.4% of participants had presence of significant depressive symptoms, and 21.2% reported a history of depression. The adjusted hazard ratio for dementia associated with baseline depressive symptoms was 1.71 (95% confidence interval, 1.37-2.13), after adjusting for age at entry, sex, educational level, and wave of enrollment. Compared with participants without depression history, those with late-life depression were at increased dementia risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.16-1.84), but early-life depression had no association with dementia risk (1.10 [0.83-1.47]). Depressed mood (adjusted hazard ratio, 1.48; 95% confidence interval, 1.25-1.76) and perceived performance difficulty (1.39 [1.15-1.67]) were independently associated with dementia. Conclusion: This study confirmed that late-life depression is associated with increased risk of dementia and supplied evidence that late-life depression may be an early manifestation of dementia rather than increasing risk for dementia. ©2011 American Medical Association. All rights reserved.


Wang L.Y.,Mental Illness Research and Education Clinical Center | Wang L.Y.,University of Washington | Murphy R.R.,Mental Illness Research and Education Clinical Center | Murphy R.R.,University of Washington | And 14 more authors.
Neurobiology of Aging | Year: 2013

Adequate central nervous system noradrenergic activity enhances cognition, but excessive noradrenergic activity may have adverse effects on cognition. Previous studies have also demonstrated that noradrenergic activity is higher in older than younger adults. We aimed to determine relationships between cerebrospinal fluid (CSF) norepinephrine (NE) concentration and cognitive performance by using data from a CSF bank that includes samples from 258 cognitively normal participants aged 21-100 years. After adjusting for age, gender, education, and ethnicity, higher CSF NE levels (units of 100 pg/mL) are associated with poorer performance on tests of attention, processing speed, and executive function (Trail Making A: regression coefficient 1.5, standard error [SE] 0.77, p= 0.046; Trail Making B: regression coefficient 5.0, SE 2.2, p= 0.024; Stroop Word-Color Interference task: regression coefficient 6.1, SE 2.0, p= 0.003). Findings are consistent with the earlier literature relating excess noradrenergic activity with cognitive impairment. © 2013.


Herskovits A.Z.,Brigham and Women's Hospital | Herskovits A.Z.,Massachusetts General Hospital | Locascio J.J.,Massachusetts General Hospital | Peskind E.R.,University of Washington | And 3 more authors.
PLoS ONE | Year: 2013

Amyloid beta (aβ) protein assembles into larger protein aggregates during the pathogenesis of Alzheimer's disease (AD) and there is increasing evidence that soluble aβ oligomers are a critical pathologic species. Diagnostic evaluations rely on the measurement of increased tau and decreased aβ42 in the cerebrospinal fluid (CSF) from AD patients and evidence for oligomeric aβ in patient CSF is conflicting. In this study, we have adapted a monoclonal single antibody sandwich ELISA assay to a Luminex platform and found that this assay can detect oligomerized aβ42 and sAPPα fragments. We evaluated oligomeric aβ reactivity in 20 patients with AD relative to 19 age matched controls and compared these values with a commercially available Alzbio3 kit that detects tau, phosphorylated tau and aβ42 on the same diagnostic platform. We found that CSF samples of patients with AD had elevated aβ oligomers compared to control subjects (p < 0.05) and the ratio of aβ oligomers to aβ42 was also significantly elevated (p < 0.0001). Further research to develop high sensitivity analytical platforms and rigorous methods of developing stable assay standards will be needed before the analysis of oligomeric aβ becomes a routine diagnostic assay for the evaluation of late onset AD patients. © 2013 Herskovits et al.


PubMed | Mental Illness Research and Education Clinical Center
Type: Journal Article | Journal: Journal of the American Geriatrics Society | Year: 2010

To examine correlations between blood pressure (BP) and dementia-related pathological brain changes in a community-based autopsy sample.Prospective cohort study.A large health maintenance organization in Seattle, Washington.A cohort of 250 participants aged 65 and older and cognitively normal at time of enrollment in the Adult Changes in Thought (ACT) Study and who underwent autopsy.BP and history of antihypertensive treatment were taken at enrollment. A linear regression model was used to examine the relationship between BP (systolic (SBP) and diastolic (DBP)) at enrollment and pathological changes in the cerebrum (cystic macroscopic infarcts, microinfarcts, neuritic plaques, neurofibrillary tangles, and cortical Lewy bodies).The presence of more than 2 microinfarcts, but not any other pathological change, was independently associated with SBP in younger participants (65-80, n=137) but not in older participants (>80, n=91). The relative risk (RR) for more than two microinfarcts with each 10-mmHg increase in SBP was 1.15 (95% confidence interval (CI)=1.00-1.33) in the younger participants, adjusted for age at entry, sex, and time to death. This RR was particularly strong in younger participants not taking antihypertensive medications (RR=1.48, 95% CI=1.21, 1.81); significant associations were not observed in participants treated for hypertension. Findings for DBP were negative.The association between high SBP and cerebrovascular damage in untreated older adults (65-80) suggests that adequate hypertension treatment may reduce dementia risk by minimizing microvascular injury to cerebrum.

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