Consuelo H. Wilkins

Regional White Matter Hyperintensity Burden in Automated Segmentation Distinguishes Late-Life Depressed Subjects From Comparison Subjects Matched for Vascular Risk Factors

OBJECTIVE 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. METHOD 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. RESULTS 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. CONCLUSIONS 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.

Vitamin D Deficiency Is Associated With Worse Cognitive Performance and Lower Bone Density in Older African Americans

BACKGROUND 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. OBJECTIVE 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. DESIGN 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. RESULTS 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. CONCLUSIONS Vitamin D deficiency in older African Americans was associated with worse cognitive performance and lower BMD of the hip.

Decreased Hippocampal 5-HT 2A Receptor Binding in Older Depressed Patients Using [ 18 F]Altanserin Positron Emission Tomography

Serotonin receptor changes have been associated with the pathophysiology and treatment of major depression. Only one other study has investigated serotonin receptor changes in older depressed patients. We used positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A receptor, to examine the relationship between 5-HT2A receptor density and depression. Depressed subjects (n=16), age>50 years, were recruited as part of a larger study. Older depressed subjects consisted of early-onset recurrent depression (EORD, n=11) and late-onset depression (LOD, n=5). An age-matched control group (n=9) was also recruited. All subjects were right-handed, nonsmokers and antidepressant-free. Regions of interest were determined on a summed MPRAGE scan transformed into Talairach space and coregistered with the PET images. Depressed subjects had less hippocampal 5-HT2A receptor binding than controls (p=0.05). No significant differences in receptor binding were found between EORD and LOD subjects. Depressed subjects not previously treated for depression (n=6) had less hippocampal 5-HT2A receptor binding (p=0.04) than previously treated subjects (n=10). It may be that prior medication treatment provides a compensatory upregulation of the 5-HT2A receptor.

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.

Dementia Undiagnosed in Poor Older Adults with Functional Impairment

OBJECTIVES: To identify variables associated with diagnosing dementia in poor older adults by comparing older people with dementia who were diagnosed by their primary care physicians (PCPs) with those not diagnosed by their PCP.

Cognitive Improvement Following Treatment in Late-Life Depression: Relationship to Vascular Risk and Age of Onset

OBJECTIVES To test the hypothesis that the degree of 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. DESIGN Measurement of cognition both before and following 12 weeks of treatment with sertraline. SETTING University medical centers (Washington University and Duke University). PARTICIPANTS One hundred sixty-six individuals with late-life depression. INTERVENTION Sertraline treatment. MEASUREMENTS 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. RESULTS 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 Examination scores predicted less change in working memory. Furthermore, older age, later age of onset, and higher vascular risk scores predicted less change in executive function. CONCLUSIONS 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.

Community Engagement Studios: A Structured Approach to Obtaining Meaningful Input From Stakeholders to Inform Research.

Problem Engaging communities in research increases its relevance and may speed the translation of discoveries into improved health outcomes. Many researchers lack training to effectively engage stakeholders, whereas academic institutions lack infrastructure to support community engagement. Approach In 2009, the Meharry-Vanderbilt Community-Engaged Research Core began testing new approaches for community engagement, which led to the development of the Community Engagement Studio (CE Studio). This structured program facilitates project-specific input from community and patient stakeholders to enhance research design, implementation, and dissemination. Developers used a team approach to recruit and train stakeholders, prepare researchers to engage with stakeholders, and facilitate an in-person meeting with both. Outcomes The research core has implemented 28 CE Studios that engaged 152 community stakeholders. Participating researchers, representing a broad range of faculty ranks and disciplines, reported that input from stakeholders was valuable and that the CE Studio helped determine project feasibility and enhanced research design and implementation. Stakeholders found the CE Studio to be an acceptable method of engagement and reported a better understanding of research in general. A tool kit was developed to replicate this model and to disseminate this approach. Next Steps The research core will collect data to better understand the impact of CE Studios on research proposal submissions, funding, research outcomes, patient and stakeholder engagement in projects, and dissemination of results. They will also collect data to determine whether CE Studios increase patient-centered approaches in research and whether stakeholders who participate have more trust and willingness to participate in research.

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 cutoff score that classifies participants as functional vs. not functional. The setting was in the Alzheimers Disease Research Center (Washington University). A total of 1199 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 cutoff 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.

Community Representatives’ Involvement in Clinical and Translational Science Awardee Activities

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.

Assessing the effectiveness of pharmacist-directed medication therapy management in improving diabetes outcomes in patients with poorly controlled diabetes.

Purpose The purpose of this study was to compare medication adherence rates and type 2 diabetes mellitus (T2DM) health outcomes in a sample of underserved patients with suboptimally controlled T2DM (A1C >7%) who had received pharmacist-directed medication therapy management (MTM) to those who had not received MTM. Methods A retrospective review of 100 patient records was conducted. For the MTM group, a pharmacist engaged patients in patient-centered services to optimize therapeutic outcomes. Non-MTM patients received usual care. Outcomes were A1C, medication adherence, blood pressure, lipids, and creatinine. Group comparisons on clinical outcomes were analyzed before and after matching MTM and non-MTM patients on demographic characteristics. Results Before matching, the MTM group had a higher rate of medication adherence than the non-MTM group. The A1C levels were lower in the MTM group compared to the non-MTM group. Similarly, low-density lipoprotein (LDL) cholesterol was lower in the MTM group compared to the non-MTM group. After matching, medication adherence rate remained higher in the MTM group than the non-MTM group. Similarly, A1C levels remained lower in the MTM group than the non-MTM group. Conclusions There is a paucity of research focused on behavioral interventions for improving health outcomes in underserved communities. Our results advance the existing literature by demonstrating a positive association between pharmacist-directed MTM, medication adherence, and glycemic control in a sample of underserved patients with suboptimally controlled T2DM. A prospective pharmacy intervention and examination of long-term effects of MTM on medication adherence and T2DM health outcomes in this population is warranted.