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1.  [No title available] 
PMCID: PMC3711958  PMID: 23567441
2.  [No title available] 
PMCID: PMC3858393  PMID: 23831171
3.  [No title available] 
PMCID: PMC3714375  PMID: 23582748
4.  [No title available] 
PMCID: PMC3947188  PMID: 24200596
5.  [No title available] 
PMCID: PMC3947219  PMID: 24080382
6.  Perceived Discrimination and Physical, Cognitive, and Emotional Health in Older Adulthood 
Objective
To examine whether perceived discrimination based on multiple personal characteristics is associated with physical, emotional, and cognitive health concurrently, prospectively, and with change in health over time among older adults.
Design
: Longitudinal
Setting
Health and Retirement Study (HRS)
Participants
Participants (N=7,622) who completed the Leave-Behind Questionnaire as part of the 2006 HRS assessment (mean age 67); participants (n=6,450) completed the same health measures again in 2010.
Measurements
Participants rated their everyday experience with discrimination and attributed those experiences to eight personal characteristics: race, ancestry, sex, age, weight, physical disability, appearance, and/or sexual orientation. At both the 2006 and 2010 assessments, participants completed measures of physical health (subjective health, disease burden), emotional health (life satisfaction, loneliness), and cognitive health (memory, mental status).
Results
Discrimination based on age, weight, physical disability, and appearance was associated with poor subjective health, greater disease burden, lower life satisfaction and greater loneliness at both assessments and with declines in health across the four years. Discrimination based on race, ancestry, sex, and sexual orientation was associated with greater loneliness at both time points, but not with change over time. Discrimination was mostly unrelated to cognitive health.
Conclusions
The detrimental effect of discrimination on physical and emotional health is not limited to young adulthood but continues to contribute to health and well-being in old age. These effects were driven primarily by discrimination based on personal characteristics that change over time (e.g., age, weight) rather than discrimination based on more stable characteristics (e.g., race, sex).
doi:10.1016/j.jagp.2014.03.007
PMCID: PMC4170050  PMID: 24745563
Discrimination; Disease Burden; Loneliness; Stress; Well-being
7.  Depressive symptoms in Chinese Americans with Cognitive Impairment 
Objectives
To assess the prevalence of geriatric depression in Chinese American patients with cognitive impairment and to compare the prevalence to that of cognitively normal elderly Chinese Americans and Caucasians.
Design
We compared rates of depressive symptomatology in elderly Chinese Americans to a matched group of Caucasians, with and without dementia, and assessed rates of treatment for depression across all groups.
Setting
Academic subspecialty referral clinic.
Participants
Participants included a total of 137 elderly, cognitively impaired and cognitively normal Chinese Americans and 140 Caucasians with and without cognitive impairment.
Measurements
Demographic (e.g. age, education, race, language ability), cognitive (MMSE score), medical (e.g. cardiovascular morbidity) and functional (Clinical Dementia Rating Scale) risk factors were assessed for association with depressive symptomatology as measured by the Geriatric Depression Scale (GDS).
Results
Depression (GDS score ≥ 6 out of 15) was significantly more common in cognitively impaired Chinese Americans (35%) versus cognitively impaired Caucasians (15%, χ2 = 33.8, p<0.05), and Chinese Americans were less likely to be on treatment for depression (12%) than Caucasians (37%, χ2 = 41, p<0.05). Cognitive and functional impairment, age and education were all independent predictors of GDS score. Rates of depression were not significantly different in cognitively normal Chinese American (6%) and Caucasian (0%) groups.
Conclusions
These findings indicate that elderly Chinese Americans with cognitive impairment are at significantly increased risk for unrecognized depression and that education, and/or other cultural factors associated with education may contribute to this risk.
doi:10.1016/j.jagp.2012.10.029
PMCID: PMC4309267  PMID: 24021225
geriatric depression; dementia; Chinese American
8.  Is sertraline treatment or depression remission in depressed Alzheimer’s patients associated with improved caregiver wellbeing? The Depression in Alzheimer’s Disease Study 2 (DIADS-2) 
Objectives
To assess if sertraline treatment (vs. placebo) or remission of depression at 12 weeks (vs. non-remission) in Alzheimer’s patients is associated with improved caregiver wellbeing.
Design
A randomized, double-blind, placebo-controlled clinical trial of the efficacy and safety of sertraline for the treatment of depression in individuals with Alzheimer’s disease.
Setting
Five clinical research sites across the United States.
Participants
Caregivers of patients enrolled in the Depression in Alzheimer’s Disease Study 2 (N=131).
Intervention
All caregivers received standardized psychosocial support throughout the study.
Measurements
Caregiver outcome measures included depression (Beck Depression Inventory), distress (Neuropsychiatric Inventory), burden (Zarit Burden Interview), and quality of life (Medical Outcomes Study Short Form Health Survey).
Results
Fifty-nine percent of caregivers were spouses, 63.4% were female, and 64.1% were white. Caregivers of patients in both treatment groups had significant reductions in distress scores over the 24 week study period, but there was not a greater benefit for caregivers of patients taking sertraline. However, caregivers of patients whose depression was in remission at week 12 had greater declines in distress scores over the 24 weeks than caregivers of patients whose depression did not remit by week 12.
Conclusions
Patient treatment with sertraline was not associated with significantly greater reductions in caregiver distress than placebo treatment. Distress but not level of depression or burden lessened for all caregivers regardless of remission status and even more so for those who cared for patients whose depression remitted. Results imply an interrelationship between caregiver distress and patient psychiatric outcomes.
doi:10.1016/j.jagp.2013.02.014
PMCID: PMC3910508  PMID: 24314887
sertraline; depression; Alzheimer’s; caregivers; DIADS-2
9.  Differences between suicide attempters and non-attempters in depressed older patients: Depression severity, white matter lesions, and cognitive functioning 
Objectives
Older adults with major depressive disorder (MDD) have the highest population-rate of suicide. White matter brain lesions (WML) are a potential biological marker for suicidality in young and middle-age adults and are correlated with cognitive impairment (CI) in older adults. In the current study of older patients with MDD, we examined 1) if a history of suicide attempts was associated with a more severe course of MDD; 2) if WML are a biological marker for suicide; and 3) if suicide attempt history is associated with CI mediated by WML.
Setting
Data from the Neurocognitive Outcomes of Depression in the Elderly.
Participants
Depressed patients (60+) who had ever attempted suicide (n=23) were compared to depressed patients (60+) who had not attempted suicide (n=223).
Measurements
Baseline and follow-up assessments were obtained for depressive symptoms (every 3 months) and cognitive functioning (every six months) over two years. Three MRI scans were conducted.
Results
At baseline, suicide attempters reported more severe past and present symptoms (e.g., depressive symptoms, current suicidal thoughts, psychotic symptoms, earlier age of onset, and more lifetime episodes) than non-attempters. Suicide attempters had more left WML at baseline, and suicide attempt history predicted a greater growth in both left and right WML. WML predicted cognitive decline; nonetheless, history of suicide attempt was unrelated to cognitive functioning.
Conclusions
Severity of depressive symptoms and WML are associated with suicide attempts in geriatric depressed patients. Suicide attempts predicted neurological changes, which may contribute to poorer long-term outcomes in elder attempters.
doi:10.1016/j.jagp.2013.01.063
PMCID: PMC4155401  PMID: 23933424
Geriatric; major depression; white matter lesions
10.  Perceived Stress Is Associated With Subclinical Cerebrovascular Disease in Older Adults 
Objective
To examine the association of perceived stress with magnetic resonance imaging (MRI) markers of subclinical cerebrovascular disease in an elderly cohort.
Design
Cross -sectional study
Setting
Community based cohort in Chicago, IL
Participants
571 adults (57% female; 58.1% African American; 41.9% non-Hispanic white; mean [SD] age=79.8 [5.9] years) from the Chicago Health and Aging Project (CHAP), an epidemiologic study of aging, completed questionnaires on perceived stress, medical history, and demographics as part of an in-home assessment, and 5 years later underwent a clinical neurological examination and magnetic resonance imaging (MRI) of the brain.
Outcome Measures
Volumetric MRI assessments of white matter hyperintensity volume (WMHV), total brain volume (TBV), and cerebral infarction.
Results
Stress was measured with 6 items from the Perceived Stress Scale (PSS); item responses, ranging from never (0) to often (3), were summed to create an overall stress score, (mean (SD) = 4.9 (3.3), range 0–18). Most participants had some evidence of vascular disease on MRI, with 153 (26.8%) having infarctions. In separate linear and logistic regression models adjusted for age, sex, education, race and time between stress assessment and MRI, each 1-point increase in PSS score was associated with significantly lower TBV (coefficient= −0.111; SE=0.049; t[563]=−2.28; P=0.023) and 7% greater odds of infarction (odds ratio=1.07; 95% CI=1.01, 1.13; Wald χ2[1]=4.90; P=0.027). PSS scores were unrelated to WMHV. Results were unchanged with further adjustment for smoking, body mass index, physical activity, history of heart disease, stroke, diabetes, and hypertension, depressive symptoms and dementia.
Conclusions
Greater perceived stress was significantly and independently associated with cerebral infarction and lower brain volume assessed 5 years later in this elderly cohort.
doi:10.1016/j.jagp.2012.06.001
PMCID: PMC3707931  PMID: 23567443
MR measures; perceived stress; biracial population sample
11.  Shape Abnormalities of the Caudate Nucleus Correlate With Poorer Gait and Balance: Results from a Subset of the LADIS Study 
Objective
Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in fronto-striatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter changes (WMC) on MRI 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.
Method
MRI scans and clinical gait/balance data (scores from the SPPB - Short Physical Performance Battery) were sourced from 66 subjects in the previously-published LADIS trial, which was performed in >65 y.o. non-disabled individuals with WMC at study entry. Data were obtained at study entry and at three-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 utilising the SPHARM toolkit.
Results
There was no correlation between the severity of WMC and striatal volumes. Caudate nuclei volume correlated with performance on the SPPB at baseline, but not at follow-up, with subsequent shape analysis showing regionalisation of left caudate changes 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 white matter changes. Striatal volume and shape changes may be suitable biomarkers for functional changes in this population.
doi:10.1016/j.jagp.2013.04.011
PMCID: PMC4234689  PMID: 23916546
12.  Socioeconomic and Psychosocial Adversity in Midlife and Depressive Symptoms Post Retirement: A 21-year Follow-up of the Whitehall II Study 
Objective
We examined whether socioeconomic and psychosocial adversity in midlife predicts post-retirement depressive symptoms.
Design and Setting
A prospective cohort study of British civil servants who responded to a self-administered questionnaire in middle-age and at older ages, 21 years later.
Participants
The study sample consisted of 3,939 Whitehall II Study participants (2,789 men, 1,150 women; mean age 67.6 years at follow-up) who were employed at baseline and retired at follow-up.
Measurements
Midlife adversity was assessed by self-reported socioeconomic adversity (low occupational position; poor standard of living) and psychosocial adversity (high job strain; few close relationships). Symptoms of depression post-retirement were measured by the Center for Epidemiologic Studies Depression scale.
Results
After adjustment for sociodemographic and health-related covariates at baseline and follow-up, there were strong associations between midlife adversities and post-retirement depressive symptoms: low occupational position (odds ratio [OR]: 1.70, 95% confidence interval [CI]: 1.15–2.51), poor standard of living (OR: 2.37, 95% CI: 1.66–3.39), high job strain (OR: 1.52, 95% CI: 1.09–2.14), and few close relationships (OR: 1.51, 95% CI: 1.12–2.03). The strength of the associations between socioeconomic, psychosocial, work-related, or non-work related exposures and depressive symptoms was similar.
Conclusions
Robust associations from observational data suggest that several socioeconomic and psychosocial risk factors for symptoms of depression post-retirement can be detected already in midlife.
doi:10.1016/j.jagp.2014.04.001
PMCID: PMC4270962  PMID: 24816123
Depression; elderly; inequalities; life course; mood disorders; old age; prospective; stress
13.  Sex Hormone Binding Globulin and Verbal Memory in Older Men 
Background
Cognitive function in older adults may be affected by multiple factors such as sex hormone levels, metabolic disturbances and neuropsychiatric illness. However, relatively few studies have tested the associations between these factors and cognitive function in a single sample. A cross-sectional analysis was conducted to examine the association between sex hormones, metabolic parameters, and psychiatric diagnoses with verbal memory in non-demented older men.
Methods
Participants included 112 men (mean age = 61.3 years) from the Baltimore Epidemiologic Catchment Area Follow-Up Study who completed measures of blood sex hormone levels, metabolic parameters (e.g. lipid profiles), and verbal memory.
Results
Higher levels of serum sex hormone binding globulin (SHBG) were associated with lower delayed verbal memory scores [standardized coefficients (beta) = −0.19, t = −2.07, df = 1, 105, p = 0.04)], and higher body mass index (BMI) was associated with better immediate (beta = 0.21, t = 2.41, df = 1,105, p = 0.02) and delayed (beta = 0.22, t = 2.46, df = 1,105, p = 0.02) verbal memory performance following adjustment for age, education, and psychiatric disorders. There was an inverse correlation between SHBG levels and BMI (Pearson’s r = −0.37, n = 112, p < 0.001). Estimated free testosterone levels revealed curvilinear associations with verbal memory performance.
Conclusion
Our data suggest that higher SHBG levels are associated with worse verbal memory, whereas a higher BMI is associated with better verbal memory in older men. Higher SHBG levels due to lower adiposity may be a risk factor for cognitive dysfunction. The mechanisms linking SHBG to cognitive function have yet to be elucidated.
doi:10.1016/j.jagp.2013.02.003
PMCID: PMC3785559  PMID: 23800538
14.  The Memory Fitness Program: Cognitive Effects of a Healthy Aging Intervention 
Context
Age-related memory decline affects a large proportion of older adults. Cognitive training, physical exercise, and other lifestyle habits may help to minimize self-perception of memory loss and a decline in objective memory performance.
Objective
The purpose of this study was to determine whether a 6-week educational program on memory training, physical activity, stress reduction, and healthy diet led to improved memory performance in older adults.
Design
A convenience sample of 115 participants (mean age: 80.9 [SD: 6.0 years]) was recruited from two continuing care retirement communities. The intervention consisted of 60-minute classes held twice weekly with 15–20 participants per class. Testing of both objective and subjective cognitive performance occurred at baseline, preintervention, and postintervention. Objective cognitive measures evaluated changes in five domains: immediate verbal memory, delayed verbal memory, retention of verbal information, memory recognition, and verbal fluency. A standardized metamemory instrument assessed four domains of memory self-awareness: frequency and severity of forgetting, retrospective functioning, and mnemonics use.
Results
The intervention program resulted in significant improvements on objective measures of memory, including recognition of word pairs (t[114] = 3.62, p < 0.001) and retention of verbal information from list learning (t[114] = 2.98, p < 0.01). No improvement was found for verbal fluency. Regarding subjective memory measures, the retrospective functioning score increased significantly following the intervention (t[114] = 4.54, p < 0.0001), indicating perception of a better memory.
Conclusions
These findings indicate that a 6-week healthy lifestyle program can improve both encoding and recalling of new verbal information, as well as self-perception of memory ability in older adults residing in continuing care retirement communities.
doi:10.1097/JGP.0b013e318227f821
PMCID: PMC4255461  PMID: 21765343
Community setting; healthy lifestyle; memory training; older adult
15.  Fatigability Disrupts Cognitive Processes' Regulation of Inflammatory Reactivity in Old Age 
Objectives
High fatigability, a dysfunctional adaption to fatigue, may lead to difficulties performing otherwise regularly encountered cognitive activities and may be related to pro-inflammatory reactivity. The purpose of the study was to investigate the effect of fatigability on cognitive processes and inflammatory response following an acute cognitive stress task in older adults.
Design
An observational laboratory stress reactivity study.
Setting
A light- and temperature-controlled laboratory.
Participants
Fifty-five community-dwelling individuals aged 75 years or older.
Measurements
We measured interleukin (IL)-6, self-reported acute fatigue, and frontally-oriented cognitive processes as part of a demanding set of cognitive tasks intended to induce stress.
Results
Subjects were classified into groups of low and high fatigability based on cluster analysis of their self-report acute fatigue before and after the cognitive tasks. The two clusters were comparable on levels of baseline IL-6 and cognitive processes; however, the high fatigability cluster had significantly higher levels of IL-6 response than the low fatigability cluster. After controlling for multiple covariates, fatigability moderated the relationship between speed of processing and IL-6 reactivity. Further exploratory analyses indicated significant adverse associations between speed of processing and attention and IL-6 reactivity in the group with low but not high fatigability.
Conclusions
While observational, these data are consistent with the notion that pro-inflammatory states in older adults might be reduced by improvements in cognitive processes. Since fatigability was associated with increased acute inflammatory response and disrupted the normal stress regulation provided by the cognitive processes, future randomized studies might examine whether fatigability alleviation reduces IL-6.
doi:10.1016/j.jagp.2013.12.003
PMCID: PMC4048650  PMID: 24388221
Fatigability; aging; attention; speed of processing; executive function; interleukin-6 reactivity
16.  The differential impact of unique behavioral and psychological symptoms for the dementia caregiver: How and why do patients’ individual symptom clusters impact caregiver depressive symptoms? 
Objectives
The behavioral and psychological symptoms associated with dementia (BPSD) are highly burdensome to caregivers. While BPSD consist of a wide variety of patient behaviors including depression, physical aggression and paranoid delusions, it remains unclear whether specific symptoms have a differential impact on caregivers. The aims of this study were (1) to assess how individual BPSD symptoms, categorized based on how they may affect caregivers, impact depressive symptoms for dementia patient caregivers and (2) to test the pathways by which BPSD symptom clusters impact caregiver depressive symptoms.
Design
Cross-sectional analysis of data from a longitudinal study of patients with Alzheimer’s disease and Dementia with Lewy Bodies.
Setting
Multiple U.S. dementia clinics.
Participants
160 patient-caregiver dyads.
Methods
Using multivariate GEE logistic models, we analyzed the relationship between four BPSD symptom clusters (patient depressive symptoms, accusatory/aggressive behaviors, non-threatening psychotic symptoms, and difficult to manage behaviors) and caregiver depressive symptoms and assessed mediators of these relationships.
Results
Only the presence of patient depressive symptoms was associated with caregiver depression (OR=1.55; 95% CI=1.14–2.1). This relationship was mediated by both caregiver report of the symptom’s impact on the patient and perceived burden to caregivers.
Conclusions
Patient depressive symptoms may be the most important driver of the relationship between BPSD and caregiver depression. Research in this field should further test the effects of individual BPSD symptoms and should also consider how symptoms may negatively impact caregivers by increasing burden and evoking empathy for the patient.
doi:10.1016/j.jagp.2013.01.062
PMCID: PMC3543497  PMID: 24206939
BPSD; caregiver depression; Alzheimer’s dementia
17.  Comorbidity Profile and Health Care Utilization in Elderly Patients with Serious Mental Illnesses 
Objectives
Patients with serious mental illness are living longer. Yet there remain few studies that focus on health care utilization and its relationship to comorbidities in these elderly mentally ill patients.
Design
Comparative study. Information on demographics, comorbidities and health care utilization were taken from an electronic medical record system.
Setting
Wishard Health Services senior care and community mental health clinics.
Participants
Patients age 65 years and over-255 patients with serious mental illness (schizophrenia, major recurrent depression and bipolar illness) attending a mental health clinic and a representative sample of 533 non-demented patients without serious mental illness attending primary care clinics.
Results
Patients having serious mental illness had significantly higher rates of medical emergency room visits (p=0.0027) and significantly longer lengths of medical hospitalizations (p<0.0001) than did the primary care control group. The frequency of medical comorbidities such as diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, thyroid disease, and cancer were not significantly different between the groups. Hypertension was lower in the mentally ill group (p<0.0001). Reported falls (p<0.0001), diagnoses of substance abuse (p=0.02), and alcoholism (p=0.0016) were higher in the seriously mentally ill. The differences in health care utilization between the groups remained significant after adjusting for comorbidity levels, lifestyle factors, and attending primary care.
Conclusions
Our findings of higher rates of emergency care, longer hospitalizations, and increased frequency of falls, substance abuse, and alcoholism suggest the elderly seriously mentally ill remain a vulnerable population requiring an integrated model of health care.
doi:10.1016/j.jagp.2013.01.056
PMCID: PMC3572246  PMID: 24206938
serious mental illness; comorbidity; health care utilization; elderly patients
18.  Defining and Assessing Wisdom: A Review of the Literature 
With increasing longevity and a growing focus on successful aging, there has been a recent growth of research designed to operationalize and assess wisdom. We aimed to (1) investigate the degree of overlap among empirical definitions of wisdom, (2) identify the most commonly cited wisdom subcomponents, (3) examine the psychometric properties of existing assessment instruments, and (4) investigate whether certain assessment procedures work particularly well in tapping the essence of subcomponents of the various empirical definitions. We searched PsychINFO-indexed articles published through May 2012 and their bibliographies. Studies were included if they were published in a peer-reviewed journal and (1) proposed a definition of wisdom or (2) discussed the development or validation of an instrument designed to assess wisdom. Thirty-one articles met inclusion criteria. Despite variability among the 24 reviewed definitions, there was significant overlap. Commonly cited subcomponents of wisdom included knowledge of life, prosocial values, self-understanding, acknowledgement of uncertainty, emotional homeostasis, tolerance, openness, spirituality, and sense of humor. Published reports describing the psychometric properties of nine instruments varied in comprehensiveness but most measures were examined for selected types of reliability and validity, which were generally acceptable. Given limitations of self-report procedures, an approach integrating multiple indices (e.g., self-report and performance-based measures) may better capture wisdom. Significant progress in the empirical study of wisdom has occurred over the past four decades; however, much needs to be done. Future studies with larger, more diverse samples are needed to determine the generalizability, usefulness, and clinical applicability of these definitions and assessment instruments. Such work will have relevance for the fields of geriatrics, psychiatry, psychology, sociology, education, and public health, among others.
doi:10.1016/j.jagp.2012.11.020
PMCID: PMC3896261  PMID: 23597933
wisdom; aging; human development; cognition; personality trait; positive psychology
19.  Are Apathy and Depression Independently Associated with Longitudinal Trajectories of Cortical Atrophy in Mild Cognitive Impairment? 
Objective
We sought to examine whether depression and apathy are independently associated with longitudinal trajectories of cortical atrophy in entorhinal cortex compared to frontal subregions previously implicated in late-life mood disturbance.
Design
Data from 334 participants classified as having Mild Cognitive Impairment (MCI) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using multilevel models for change adjusted for age, global cognitive status, and total intracranial volume at enrollment.
Setting
Participants in ADNI were recruited from over 50 clinical research sites in the United States and Canada.
Measurements
Depression and apathy were identified by informants with the Neuropsychiatric Inventory Questionnaire. Serial MRI was carried out on 1.5T scanners according to standardized ADNI-1 protocol on an average of 5 occasions over an average of 2.5 years. Regional cortical thickness values were derived from longitudinal data processing in Freesurfer version 4.4.
Results
Depression was associated with reduced cortical thickness in the entorhinal cortex at baseline and accelerated atrophy in anterior cingulate cortex. Similarly-sized relationships between depression and orbitofrontal cortex and between apathy and anterior cingulate cortex were not significant.
Conclusions
In MCI, depression signs are a better marker of longitudinal cortical atrophy than apathy. Results are consistent with hypotheses that depression is an early sign of a more aggressive neurodegenerative process or that depression lowers brain reserve capacity, allowing for more rapid progression of AD neuropathology.
doi:10.1016/j.jagp.2013.01.043
PMCID: PMC3797189  PMID: 23636003
MRI; Alzheimer’s disease; mild cognitive impairment; apathy; depression
20.  Phobic anxiety and cognitive performance over 4 years among community-dwelling older women in the Nurses’ Health Study 
Objective
To examine the relation of phobic anxiety to late-life cognitive trajectory.
Design
Prospective cohort.
Setting
Nurses’ Health Study – U.S. registered nurses.
Participants
16,351 women among whom phobic anxiety symptoms were assessed in 1988 (mean age=63 years).
Measurements
Beginning a decade after phobic anxiety ascertainment (mean age=74 years), three assessments of general cognition, word and paragraph immediate and delayed recall, category fluency, and attention/working memory were administered over an average of 4.4 years; global cognitive and verbal memory composite scores were generated from the component tests. General linear models of response profiles were used to evaluate relations of phobic anxiety to initial cognitive performance and subsequent change.
Results
Higher phobic anxiety was associated with poorer initial performance: e.g., comparing women with the highest anxiety to those with no/minimal symptoms, the multivariate-adjusted mean difference (95% confidence interval) in scores was −0.10 (−0.13,−0.06) standard units for the global score summarizing all tests, and −0.08 (−0.11,−0.04) standard units for verbal memory (summarizing 4 word- and paragraph-recall tasks). Mean differences between extreme categories of phobic anxiety were equal to those for participants aged 1.5–2 years apart: i.e., cognitively equivalent to being about two years older. There were no relations of phobic anxiety to subsequent cognitive change.
Conclusions
Higher mid-life phobic anxiety was related to worse later-life overall cognition and verbal memory. Yet, profiles of poorer cognition with higher anxiety remained parallel over time, suggesting phobic anxiety may impose impact on cognition earlier in life, rather than ongoing impact in later-life.
doi:10.1016/j.jagp.2013.01.050
PMCID: PMC3516630  PMID: 23567369
21.  Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: The Cache County Study 
Objectives
To examine the association of neuropsychiatric symptom (NPS) severity with risk of transition to all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD).
Design
Survival analysis of time to dementia, AD, or VaD onset.
Setting
Population-based study.
Participants
230 participants diagnosed with cognitive impairment, no dementia (CIND) from the Cache County Study of Memory Health and Aging were followed for a mean of 3.3 years.
Measurements
The Neuropsychiatric Inventory (NPI) was used to quantify the presence, frequency, and severity of NPS. Chi-square statistics, t-tests, and Cox proportional hazard ratios were used to assess associations.
Results
The conversion rate from CIND to all-cause dementia was 12% per year, with risk factors including an APOE ε4 allele, lower MMSE, lower 3MS, and higher CDR sum-of-boxes. The presence of at least one NPS was a risk factor for all-cause dementia, as was the presence of NPS with mild severity. Nighttime behaviors were a risk factor for all-cause dementia and of AD, while hallucinations were a risk factor for VaD.
Conclusions
These data confirm that NPS are risk factors for conversion from CIND to dementia. Of special interest is that even NPS of mild severity are a risk for all-cause dementia or AD.
doi:10.1016/j.jagp.2013.01.049
PMCID: PMC3525756  PMID: 23567370
CIND; MCI; NPS; NPI; Cache County; dementia; depression; agitation; anxiety
22.  Late-life Mental Health Education for Workforce Development: Brain vs. Heart? 
Purpose
There is a shortage of mental health professionals to care for a growing geriatric population. Though not mutually exclusive, clinical and didactic educational experiences promote cognition, while affective knowledge (attitude) is promoted through non-clinical exposure to seniors. This study evaluates the relative impact of cognition and attitude on career interests among healthcare students.
Methods
We developed thirteen interactive, video-documentary “lessons” on late-life mental health presenting didactic material along with stories of actual patients and families. Four of these lessons were viewed at one week intervals by forty-two students from medical school and graduate programs of social work, psychology, and nursing. Knowledge, attitudes, and inclinations towards working with seniors were assessed.
Results
Both cognition and attitudes towards seniors improved. Linear regression shows change in attitude, not cognition, predicts interest in working with seniors.
Conclusion
Educational experiences that promote affective learning may enhance interest in geriatric careers among healthcare students.
doi:10.1016/j.jagp.2013.01.031
PMCID: PMC3594556  PMID: 23567380
Geriatric Education; Workforce development; Late-life mental health education
23.  Personality factors moderate the associations between Apolipoprotein genotype and cognitive function as well as late onset Alzheimer’s Disease 
Objectives
We tested the hypothesis that neuroticism moderates the association between APOE (apolipoprotein E) genotype and two major outcomes, cognitive function and Alzheimer’s disease (AD). We also explored whether other personality dimensions (extraversion, openness to experience, agreeableness, and conscientiousness) moderate the associations of APOE with these outcomes.
Design
Primary analyses of existing randomized clinical trial data.
Sample
Six-hundred and two older adults (mean age of 78 at baseline).
Measurements
APOE genotype, the NEO-Five Factor Inventory, the Alzheimer’s Disease Assessment Scale- cognitive (ADAS-COG: measured every 6 months for 6.5 years) and relevant covariates.
Results
Fully adjusted multivariate analyses showed that the association between the presence of APOE ε-4 allele(s) and both outcomes was evident among individuals with high levels of neuroticism and extraversion but not among persons with low levels of these traits.
Conclusions
Phenotypic personality dimensions, primarily neuroticism and extraversion, moderate the relationship between APOE ε-4 genotype and cognitive outcomes among older adults. Future research is needed to elucidate the physiological processes involved in these particular phenotype-genotype interactions.
doi:10.1097/JGP.0b013e318267016b
PMCID: PMC4184145  PMID: 23079898
G x E interaction; Alzheimer’s disease; cognitive function; APOE genotype; personality
24.  Racial Differences in Adherence to Antidepressant Treatment in Later Life 
Objective
Although antidepressants are an effective treatment for later-life depression, older patients often choose not to initiate or to discontinue medication treatment prematurely. While racial differences in depression treatment preferences have been reported, little is known about racial differences in antidepressant medication adherence among older patients.
Design
Prospective, observational study comparing antidepressant adherence for older African-American and white primary care patients.
Participants
One hundred and eighty-eight subjects aged 60 and older, diagnosed with clinically significant depression with a new recommendation for antidepressant treatment by their primary care physician.
Measurement
Study participants were assessed at study entry and at four-month follow-up (encompassing the acute treatment phase). Depression medication adherence was based on a well-validated self-report measure.
Results
At four-month follow-up, 61.2% of subjects reported that they were adherent to their antidepressant medication. In unadjusted and two of the three adjusted analyses, African-American subjects (n=82) had significantly lower rates of four-month antidepressant adherence than white subjects (n=106). African-American females had the lowest adherence rates (44.4%) followed by African-American males (56.8%), white males (65.3%) and white females (73.7%). In logistic regression models controlling for demographic, illness, and functional status variables, significant differences persisted between African-American women and white women in reported four-month antidepressant adherence (OR 3.58, 95% CI 1.27-10.07, Wald Chi-square =2.42, df=1, p<0.02).
Conclusions
The results demonstrate racial and gender differences in antidepressant adherence in older adults. Depression treatment interventions for the older adults should take into account the potential impact of race and gender on adherence to prescribed medications.
doi:10.1016/j.jagp.2013.01.046
PMCID: PMC3573214  PMID: 23602306
25.  Does preoperative risk for delirium moderate the effects of postoperative pain and opiate use on postoperative delirium? 
Objectives
To investigate whether preoperative risk for delirium moderates the effect of postoperative pain and opioids on the development of postoperative delirium.
Design
Prospective cohort study
Setting
University medical center
Participants
Patients ≥ 65 years of age scheduled for major noncardiac surgery
Measurements
A structured interview was conducted pre- and post-operatively to determine the presence of delirium, defined using the Confusion Assessment Method. We first developed a prediction model to determine which patients were at high vs. low risk for the development of delirium based on preoperative patient data. We then computed a logistic regression model to determine whether preoperative risk for delirium moderates the effect of postoperative pain and opioids on incident delirium.
Results
Of 581 patients, 40% developed delirium on days 1 or 2 after surgery. Independent preoperative predictors of postoperative delirium included lower cognitive status, a history of central nervous system disease, high surgical risk, and major spine and joint arthroplasty surgery. Compared to the patients at low preoperative risk for developing delirium, the relative risk for postoperative delirium for those in the high preoperative risk group was 2.38 (95% CI = 1.67–3.40). A significant three-way interaction indicates that preoperative risk for delirium significantly moderated the effect of postoperative pain and opioid use on the development of delirium. Among patients at high preoperative risk for development of delirium who also had high postoperative pain and received high opioid doses, the incidence of delirium was 72%, compared to 20% among patients with low preoperative risk, low postoperative pain and received low opioid doses.
Conclusions
High levels of postoperative pain and using high opioid doses increased risk for postoperative delirium for all patients. However, the highest incidence of delirium was among patients who had high preoperative risk for delirium and also had high postoperative pain and used high opioid doses.
doi:10.1016/j.jagp.2013.01.069
PMCID: PMC3742555  PMID: 23659900

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