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1.  Mild Physical Impairment Predicts Future Diagnosis of Dementia of the Alzheimer Type 
Journal of the American Geriatrics Society  2013;61(7):10.1111/jgs.12255.
To determine whether mildly impaired physical function (based on performance-based assessment) is associated with the development of dementia of the Alzheimer type (DAT) in cognitively normal older adults.
Longitudinal, observational study with yearly assessments of physical and cognitive function. Mean follow-up was 5 years.
Knight Alzheimer’s Disease Research Center at Washington University, St. Louis, Missouri.
Four hundred thirty-five cognitively normal adults, age 60 years or older participating in longitudinal studies of aging.
Survival analyses were used to examine whether scores on the 9-item Physical Performance Test (PPT) predicted time to DAT diagnosis. Cox proportional hazards models were used to examine associations between the PPT total scores and time to cognitive impairment and DAT; as well as the association of time to these events while adjusting for, and simultaneously testing the effects of age, gender, education, and presence of at least one apolipoprotein (APOE) ε4 allele.
During the follow-up period, 81 participants developed DAT. Compared to those who remained cognitively normal, participants diagnosed with DAT were older (81 vs 74.2 years; p=.001) and had worse performance on the PPT (25.5 vs 28.1; p=.009). Time to DAT diagnosis was associated with total scores on the PPT (hazard ratio [HR] =.89, 95% CI=.86–.93, p<.001) such that time to a DAT diagnosis was slower for participants with higher physical performance scores. In the adjusted analysis, the PPT scores significantly predicted time to a DAT diagnosis (HR =.94, 95% CI=.89–.99, p<.022).
The presence of mild physical impairment in cognitively normal older adults is associated with subsequent development of DAT. Although the physical impairment may be sufficiently mild that it is recognized only with performance-based assessments, its presence may predate clinically detectable cognitive decline.
PMCID: PMC3809089  PMID: 23647233
Dementia of Alzheimer type; physical performance; predictors; frailty
2.  Vitamin D Deficiency Is Associated With Worse Cognitive Performance and Lower Bone Density in Older African Americans 
Vitamin D deficiency is common in older adults and is more prevalent among persons with darker pigmented skin. The detrimental effects of vitamin D deficiency on the bone are widely known; however, recent data suggest that vitamin D deficiency may contribute to other disorders, including low mood, cognitive impairment, and impaired mobility.
The purpose of this study was to determine whether nonskeletal diseases such as depression, cognitive impairment, and physical disability, which have been associated with vitamin D deficiency, are more commonly seen in older African Americans.
In a cross-sectional study of 60 older adults (30 African Americans and 30 European Americans), vitamin D status, cognitive performance, physical performance, and bone mineral density (BMD) were assessed. Differences between groups and differences between those with vitamin D deficiency and those with normal vitamin D levels were tested.
African Americans had a lower mean 25-hydroxyvitamin D level (17.98 ng/ml; SD, 6.9) compared to European Americans (25.20 ng/ml; SD, 7.0; p < .0001). Participants with vitamin D deficiency performed worse on a measure of cognitive performance, the Short Blessed Test (10.87 vs 6.31; p = .016); the Physical Performance Test (PPT) (27.00 vs 28.96; p = .039); and had lower BMD (0.823 vs 0.914; p = .005) and t scores (−1.29 vs −0.72; p = .008) of the hip. Among African Americans, vitamin D deficiency was associated with worse cognitive performance and lower BMD of the hip.
Vitamin D deficiency in older African Americans was associated with worse cognitive performance and lower BMD of the hip.
PMCID: PMC2801439  PMID: 19397226
vitamins and minerals; African Americans; cognitive functioning; bone
3.  Late life depression with cognitive impairment: Evaluation and treatment 
Older adults with depression often present with signs and symptoms indicative of functional or cognitive impairment. These somatic symptoms make evaluating and treating depression in older adults more complex. Late life depression (LLD), depression in adults over the age of 65, is more frequently associated with cognitive changes. Cognitive impairment in LLD may be a result of the depressive disorder or an underlying dementing condition. Memory complaints are also common in older adults with depression. There is a wide range of cognitive impairment in LLD including decreased central processing speed, executive dysfunction, and impaired short-term memory. The etiology of cognitive impairment in LLD may include cerebrovascular disease, a significant risk factor for LLD, which likely interrupts key pathways between frontal white matter and subcortical structures important in mood regulation. Because depressive symptoms often coexist with dementia, it is important to determine the temporal relationship between depressive symptoms and cognitive change. If depressive symptoms pre-date the cognitive impairment and cognitive symptoms are mild and temporary, LLD is the likely etiology of the cognitive impairment. If cognitive changes appear prior to depressive symptoms and persist after LLD is successfully treated, an underlying dementia is more likely. Clinicians should be exclude common conditions such as thyroid disease which can contribute to depressive symptoms and cognitive impairment prior to treating LLD. Both antidepressants and psychotherapy can be effective in treating LLD. Subsequent evaluations following treatment should also reassess cognition.
PMCID: PMC2685224  PMID: 19503765
late life depression; cognitive impairment; diagnosis; treatment; cognition
4.  Osteoporosis screening and risk management 
Clinical Interventions in Aging  2007;2(3):389-394.
Osteoporosis is common among older adults and results in costly osteoporotic fractures. Screening for this metabolic bone disorder is warranted in most older adults and clinicians must be diligent in identifying persons at risk. The evaluation should include an assessment of risk factors for falls, a bone density test, and consideration of possible secondary causes of osteoporosis. Several medications are available to improve bone density and decrease fractures. Adequate calcium and vitamin D intake (and treatment of vitamin D deficiency) are paramount in the management of osteoporosis.
PMCID: PMC2685263  PMID: 18044189
Osteoporosis; Fractures; Vitamin D
5.  Osteoporosis screening is unjustifiably low in older African-American women. 
BACKGROUND: More than one million Americans suffer osteoporotic fractures yearly, resulting in a marked increase in morbidity and mortality. Despite a decrease in bone mineral density with increasing age in all ethnic groups and both genders, preventative and therapeutics efforts in osteoporosis have been focused on caucasian and Asian women. This study assesses the osteoporosis screening practices and the frequency of low bone density in a primarily African-American population of older women. METHODS: Medical records of 252 women at risk for osteoporosis were reviewed for the diagnosis of osteoporosis, prior osteoporosis screening, prior breast cancer screening, and the use of calcium, vitamin D or estrogen. Subsequently, 128 women were assessed for risk factors for osteoporosis, and their bone mineral density was measured using a peripheral bone densitometer. RESULTS: Osteoporosis screening had been performed in 11.5% of the subjects. Of the women evaluated by peripheral bone densitometry, 44.5% of all women, 40.4% of African-American women, and 53.3% of caucasian women had abnormally low bone density measurements. The frequency of abnormal bone density increased with both increasing age and decreasing body mass index. CONCLUSIONS: Although few women in this population were previously screened for osteoporosis, low bone density occurred in African-American women at substantial rates. Increasing age and low body mass are important risk factors for low bone density in African-American women. Ethnicity should not be used as an exclusion criterion for screening for osteoporosis.
PMCID: PMC2595016  PMID: 15101666
6.  Community Representatives’ Involvement in Clinical and Translational Science Awardee Activities 
Objectives: To understand the formal roles of community representatives (CRs) in Clinical and Translational Science Awardee (CTSA) activities, to evaluate the extent of integration into the organizational and governance structures and to identify barriers to effective integration.
Methods: The inventory tool was distributed to each of the 60 CTSAs using a secure web application.
Results: Forty-seven (78%) completed the inventory. The mean number of CRs per CTSA is 21.4 (SD: 14.8). Most CTSAs had community advisory boards (89%) and 94% included CRs in Community Engagement (CE) cores. Only 11% reported a CR being a member of the CTSA leadership team and 19% reported that CRs advise core programs beyond CE.
CRs are compensated by 79% of CTSAs. Mean annual compensation is $753 (median: $400). Compensation directly correlated with the number of hours that CRs worked in CTSA activities (r = 0.64; P = 0.001).
Conclusions: This inventory allows CTSAs to better understand how CRs have engaged in activities and brings attention to the limited representation among cores and in leadership roles. CTSAs should, with substantive input from CRs, develop strategies to provide the resources and compensation necessary to better integrate the community in CTSA activities and fully realize the goals of the CTSA vision.
PMCID: PMC3884765  PMID: 23919364
community engagement; CTSA; community-engaged research; translational research
7.  Regional White Matter Hyperintensity Burden in Automated Segmentation Distinguishes Late-Life Depressed Subjects From Comparison Subjects Matched for Vascular Risk Factors 
The American journal of psychiatry  2008;165(4):524-532.
Segmented brain white matter hyperintensities were compared between subjects with late-life depression and age-matched subjects with similar vascular risk factor scores. Correlations between neuropsychological performance and whole brain-segmented white matter hyperintensities and white and gray matter volumes were also examined.
Eighty-three subjects with late-life depression and 32 comparison subjects underwent physical examination, psychiatric evaluation, neuropsychological testing, vascular risk factor assessment, and brain magnetic resonance imaging (MRI). Automated segmentation methods were used to compare the total brain and regional white matter hyperintensity burden between depressed patients and comparison subjects.
Depressed patients and comparison subjects did not differ in demographic variables, including vascular risk factor, or whole brain-segmented volumes. However, depressed subjects had seven regions of greater white matter hyperintensities located in the following white matter tracts: the superior longitudinal fasciculus, fronto-occipital fasciculus, uncinate fasciculus, extreme capsule, and inferior longitudinal fasciculus. These white matter tracts underlie brain regions associated with cognitive and emotional function. In depressed patients but not comparison subjects, volumes of three of these regions correlated with executive function; whole brain white matter hyperintensities correlated with executive function; whole brain white matter correlated with episodic memory, processing speed, and executive function; and whole brain gray matter correlated with processing speed.
These findings support the hypothesis that the strategic location of white matter hyperintensities may be critical in late-life depression. Further, the correlation of neuropsychological deficits with the volumes of whole brain white matter hyperintensities and gray and white matter in depressed subjects but not comparison subjects supports the hypothesis of an interaction between these structural brain components and depressed status.
PMCID: PMC4118770  PMID: 18281408
8.  Cognitive Improvement Following Treatment in Late Life Depression: Relationship to Vascular Risk and Age of Onset 
To test the hypothesis that the degree vascular burden and/or age of onset may influence the degree to which cognition can improve during the course of treatment in late life depression.
Measurement of cognition both prior to and following 12-weeks of treatment with Sertraline.
University Medical Centers (Washington University and Duke University)
166 individuals with late life depression.
Sertraline treatment.
The cognitive tasks were grouped into five domains (language, processing speed, working memory, episodic memory, and executive function). We measured vascular risk using the Framingham Stroke Risk Profile measure. We measured T2 based white matter hyperintensities using the Fazekas criteria.
Both episodic memory and executive function demonstrated significant improvement among adults with late life depression during treatment with sertraline. Importantly, older age, higher vascular risk scores, and lower baseline Mini-Mental state exam scores predicted less change in working memory. Further, older age, later age of onset, and higher vascular risk scores predicted less change in executive function.
These results have important clinical implications, in that they suggest that a regular assessment of vascular risk in older adults with depression is necessary as a component of treatment planning and in predicting prognosis, both for the course of the depression itself and for the cognitive impairments that often accompany depression in later life.
PMCID: PMC3382028  PMID: 22430020
Cognition; Vascular Depression; Treatment; white matter
9.  A brief clinical tool to assess physical function: The mini physical performance test 
The aim was to develop a brief physical performance assessment tool that can be reliably used to detect physical impairment in older adults with and without mild dementia. Scores on the 9-item physical performance test (PPT) from non-demented participants were used to develop and validate the 4-item mini-PPT. The validated mini-PPT was then used to predict total PPT score and functional physical status in participants with mild dementia. Receiver Operating Curve (ROC) analyses were used to generate a cut off score that classifies participants as functional vs. not functional. The setting was in the Alzheimer’s Disease Research Center (Washington University). A total of 1,199 participants met inclusion criteria: 574 non demented participants, 436 with very mild dementia, measured by the clinical dementia rating (CDR) = 0.5 and 189 with mild dementia (CDR = 1). The mean age of the sample was 76.4 years, mean educational attainment was 14 years, 58% were women, and 11% were African American. A 4-item scale, the mini-PPT, was developed (based on the results of multiple regression analyses and clinical meaningfulness) that highly correlated with total PPT score (r = 0.917, p < 0.0001) in the non-demented sample The correlation of the mini-PPT with total PPT was 0.90 among those with very mild, and 0.91 among those with mild dementia. Using the ROCs, a cut off score of 12 correctly classified at least 85% of non demented and demented persons. The 4-item mini-PPT is highly correlated with the 9-item PPT in non demented and mildly demented persons. This brief tool may be useful in detecting early physical impairment in the clinical setting.
PMCID: PMC2787987  PMID: 19282039
physical performance; assessment of physical performance; Alzheimer’s disease; dementia

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