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1.  Caregiver Burden in Alzheimer’s Disease: Cross Sectional and Longitudinal Patient Correlates 
Objectives
Alzheimer disease (AD) imposes a severe burden upon patients and their caregivers. Although there is substantial evidence of the adverse impact of burden, considerably less is known about its specific correlates and potential causes.
Design
We use data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-AD study to examine the relationship of burden and depression among AD caregivers to patient and caregiver sociodemographic characteristics, patients’ cognitive status, psychiatric and behavioral symptoms, functional abilities, quality of life, and intensity of care provided by caregivers.
Setting
CATIE-AD included outpatients in usual care settings, and assessed treatment outcomes over nine-months.
Participants
Data were examined from 421 ambulatory outpatients with a diagnosis of dementia of the Alzheimer's type or probable AD with agitation or psychosis.
Measures
The Burden Interview, the Beck Depression Inventory, and the Caregiver Distress Scale were used to evaluate caregiver burden.
Results
More severe psychiatric and behavioral problems and decreased patient quality of life, as well as lower functional capability were significantly associated with higher levels of burden and depression among caregivers at baseline. Six month changes showed that decreased symptoms and improved quality of life were associated with decreased burden and accounted for most of the explained variance in change in burden measures.
Conclusion
Severity of psychiatric symptoms, behavioral disturbances and patients’ quality of life are the main correlates of caregivers’ experience burden. Psychosocial and pharmacologic interventions targeting these two aspects of the disorder are likely to not only alleviate patient suffering but also promote caregiver well-being.
doi:10.1097/JGP.0b013e3181d5745d
PMCID: PMC3972419  PMID: 20808108
Caregivers Burden; Alzheimer’s Disease; Antipsychotics
2.  Decision Making for Participation in Dementia Research 
Objectives
This study examined the decision-making process used by individuals asked to participate in dementia research and their opinions on how future proxy research decisions would or should be made, including participants’ preferred ethical standards for decision-making.
Design
Cross-sectional qualitative methods.
Setting
University research institutions.
Participants
Informants were 39 of 46 cognitively impaired individuals (i.e., subjects) who were asked to join one of six dementia studies and 46 study partners or surrogate decision-makers.
Measurements
Semi-structured individual interviews were audio recorded and transcribed for content analysis.
Results
Within dyads, subjects and surrogates often differed in their perspectives on how decisions were made regarding whether to join a study, and no single method was identified as a predominant approach. While there was only fair agreement within dyads on who ultimately made the decision, subjects and surrogates most often said it was the subject. For future proxy research decisions, subjects and surrogates most often preferred the ethical standard of best interests and least often favored substituted judgment. However, many participants preferred a combination of best interests and substituted judgment or a more complex approach that also considers the interests of others.
Conclusions
Individuals with mild to moderate cognitive impairment can and do engage to some extent in the decision-making process for dementia research and can discuss their opinions on how they would want such decisions made for them in the future. These findings support the recommended approach for obtaining proxy consent and subject assent if the individual lacks consent capacity.
doi:10.1016/j.jagp.2012.11.009
PMCID: PMC3381948  PMID: 23498382
Dementia; Clinical research; Decision making; Qualitative research
3.  Phenotyping Apathy in Individuals With Alzheimer Disease Using Functional Principal Component Analysis 
Objectives
To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer disease (AD).
Design
Examination of ad libitum 24-hour ambulatory gross motor activity patterns.
Setting
Community-dwelling, outpatient.
Participants
Ninety-two individuals with AD, 35 of whom had apathy.
Measurements
Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA).
Results
Individuals with apathy have a different pattern of gross motor activity than those without apathy (first fPCA component, p <0.0001, t = 5.73, df = 90, t test) such that there is a pronounced decline in early afternoon activity in those with apathy. This change in activity is independent of depression (p = 0.68, F[1, 89] = 0.05, analysis of variance). The decline in activity is consistent with an increase in napping. Those with apathy also have an early wake and bedtime (second fPCA component, t = 2.53, df = 90, p <0.05, t test).
Conclusions
There is a signature activity pattern in individuals with apathy and AD that is distinct from those without apathy and those with depression. Actigraphy may be a useful adjunctive measurement in the clinical diagnosis of apathy in the context of AD.
doi:10.1016/j.jagp.2012.12.012
PMCID: PMC3603283  PMID: 23498386
Alzheimer disease; actigraphy; apathy; circadian; functional data analysis; sleep
4.  Clinical and Ethical Aspects of Financial Capacity in Dementia: A Commentary 
In contrast to issues like treatment and research consent capacity, financial capacity has received relatively little clinical and ethical attention in the dementia literature. Yet issues of financial capacity emerge frequently in patients with Alzheimer's disease (AD), Parkinson's disease (PD) and related dementias, and commonly present ethical and clinical challenges for clinicians treating these patients. These issues include whether a patient with possible dementia has sufficient capacity independently to manage their financial affairs, needs referral for financial capacity assessment, and/or is being financially exploited or abused by others. The accurate identification, assessment and successful handling of such financial capacity issues can have a substantial impact on the financial and psychological well-being of patients and their family members. The present commentary presents an overview of financial capacity and associated clinical and ethical issues in dementia, and describes a set of possible clinician roles regarding these issues as they arise in clinical practice. The commentary concludes with a section describing educational resources available to clinicians and bioethicists seeking additional guidance in handling financial capacity issues. The ultimate goal of the paper is to focus clinical and ethical attention on a neglected capacity that is of fundamental importance for patients, families, and health care and legal professionals.
doi:10.1097/JGP.0b013e31826682f4
PMCID: PMC3784311  PMID: 24078779
5.  Psychological Well-Being and Regional Brain Amyloid and Tau in Mild Cognitive Impairment 
Objectives
To determine whether psychological well-being in people with mild cognitive impairment (MCI), a risk state for Alzheimer disease (AD), is associated with in vivo measures of brain pathology.
Methods
Cross-sectional clinical assessments and positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene) malononitrile (FDDNP), a molecule that binds to plaques and tangles, were performed on middle-aged and older adults at a university research institute. Volunteers were aged 40–85 years with MCI (N = 35) or normal cognition (N = 29) without depression or anxiety. Statistical analyses included general linear models, using regional FDDNP-PET binding values as dependent variables and the Vigor-Activity subscale of the Profile of Mood States (POMS) as the independent variable, covarying for age. The POMS is a self-rated inventory of 65 adjectives that describe positive and negative feelings.
Results
Scores on the POMS Vigor-Activity subscale were inversely associated with degree of FDDNP binding in the posterior cingulate cortex (r = −0.35, p = 0.04) in the MCI group but not in the control group.
Conclusion
Psychological well-being, as indicated by self-reports of greater vigor and activity, is associated with lower FDDNP-PET binding in the posterior cingulate cortex, a region involved in emotional regulation, in individuals with MCI but not in those with normal cognition. These findings are consistent with previous work indicating that deposition of brain amyloid plaques and tau tangles may result in noncognitive and cognitive symptoms in persons at risk for AD.
doi:10.1016/j.jagp.2012.09.002
PMCID: PMC3883933  PMID: 23567426
Aging; FDDNP; positron emission tomography; POMS; well-being
6.  Staff Training in Assisted Living: Evaluating Treatment Fidelity 
Objectives
To investigate a protocol for identifying and evaluating treatment fidelity in STAR (Staff Training in Assisted-living Residences), a structured yet flexible program to train direct care staff to improve care of residents with dementia.
Design
Multi-site feasibility trial.
Setting
Assisted living facilities (ALFs).
Participants
44 direct care staff and 36 leadership staff.
Intervention
STAR is a comprehensive, dementia-specific training program to teach direct care staff in ALFs to improve care and reduce affective and behavioral problems in residents with dementia. It is conducted on-site over two months via 2 half-day group workshops and 4 individualized sessions.
Measures
Treatment fidelity was assessed following the National Institute of Health Behavior Change Consortium model utilizing observations and self-report of trainers, direct care staff and leadership.
Results
Each key area of treatment fidelity was identified, measured, and yielded significant outcomes. For example, significant increases included: direct care staff identifying ABCs (an essential component of training); understanding basics of dementia care; and applying STAR techniques.
Conclusions
Results support that STAR is ready to be translated and disseminated into practice. Because ALFs will continue to provide care for individuals with dementia, the need for effective, practical, and sustainable staff training programs is clear. STAR offers one such option. Hopefully, this report will encourage others to conduct comprehensive evaluations of the treatment fidelity of their programs and thereby increase the availability of such programs to enhance care.
doi:10.1097/JGP.0b013e3181c37b0e
PMCID: PMC3972022  PMID: 19910884
Assisted Living; Dementia Care; Staff Training
7.  Serotonin Transporter Occupancy and the Functional Neuroanatomic Effects of Citalopram in Geriatric Depression 
Objectives
The functional neuroanatomic changes associated with selective serotonin reuptake inhibitor (SSRI) treatment have been the focus of positron emission tomography (PET) studies of cerebral glucose metabolism in geriatric depression.
Design
To evaluate the underlying neurochemical mechanisms, the present study measured both cerebral glucose metabolism and serotonin transporter (SERT) availability prior to and during treatment with the SSRI, citalopram. It was hypothesized that SERT occupancy would be observed in cortical and limbic brain regions that have shown metabolic effects, as well as striatal and thalamic regions that have been implicated in prior studies in mid-life patients.
Setting
Psychiatric Outpatient Clinic.
Participants
Seven depressed patients who met DSM-IV criteria for current major depressive episode were enrolled.
Intervention
Patients underwent a twelve week open-label trial of the SSRI, citalopram.
Measurements
Patients underwent high resolution research tomography (HRRT) PET scans to measure changes in cerebral glucose metabolism and SERT occupancy by citalopram treatment (after 8–10 weeks of treatment).
Results
Three different tracer kinetic models were applied to the [11C]-DASB region of interest data and yielded similar results of an average of greater than 70% SERT occupancy in the striatum and thalamus during citalopram treatment. Voxel-wise analyses showed significant SERT occupancy in these regions, as well as cortical (e.g. anterior cingulate, superior and middle frontal, precuneus, and limbic (parahippocampal gyrus) areas that also showed reductions in glucose metabolism.
Conclusions
The findings suggest that cortical and limbic SERT occupancy may be an underlying mechanism for the regional cerebral metabolic effects of citalopram in geriatric depression.
doi:10.1097/JGP.0b013e318227f83f
PMCID: PMC3968900  PMID: 21841458
selective serotonin reuptake inhibitors; citalopram; serotonin; Positron Emission Tomography (PET); glucose metabolism; serotonin transporter; depression; aging
9.  Randomized controlled trial of cognitive behavioral social skills training for older consumers with schizophrenia: Defeatist performance attitudes and functional outcome 
Objectives
To determine whether cognitive behavioral social skills training (CBSST) is an effective psychosocial intervention to improve functioning in older consumers with schizophrenia, and whether defeatist performance attitudes are associated with change in functioning in CBSST.
Design
An 18-month, single-blind, randomized controlled trial.
Setting
Outpatient clinic at a university-affiliated Veterans Affairs hospital.
Participants
Veteran and non-veteran consumers with schizophrenia or schizoaffective disorder (N=79) age 45–78.
Interventions
CBSST was a 36-session, weekly group therapy that combined cognitive behavior therapy with social skills training and problem solving training to improve functioning. The comparison intervention, goal-focused supportive contact (GFSC), was supportive group therapy focused on achieving functioning goals.
Measurements
Blind raters assessed functioning (primary outcome: Independent Living Skills Survey) CBSST skill mastery, positive and negative symptoms, depression, anxiety, defeatist attitudes, self-esteem, and life satisfaction.
Results
Functioning trajectories over time were significantly more positive in CBSST than in GFSC, especially for participants with more severe defeatist performance attitudes. Greater improvement in defeatist attitudes was also associated with better functioning in CBSST, but not GFSC. Both treatments showed comparable significant improvements in amotivation, depression, anxiety, positive self-esteem and life satisfaction.
Conclusions
CBSST is an effective treatment to improve functioning in older consumers with schizophrenia, and both CBSST and other supportive goal-focused interventions can reduce symptom distress, increase motivation and self esteem, and improve life satisfaction. Participants with more severe defeatist performance attitudes may benefit most from cognitive behavioral interventions that target functioning.
doi:10.1016/j.jagp.2012.10.014
PMCID: PMC3467335  PMID: 23395192
10.  Neuropsychological Predictors of Dementia in Late-Life Major Depressive Disorder 
Objective
Major Depressive Disorder (MDD) is a likely risk factor for dementia, but some cases of MDD in older adults may actually represent a prodrome of this condition. The purpose of this study was to use neuropsychological test scores to predict conversion to dementia in a sample of depressed older adults diagnosed as nondemented at time of neuropsychological testing.
Design
Longitudinal, with mean follow-up of 5.45 years.
Setting
Outpatient depression treatment study at Duke University
Participants
30 nondemented individuals depressed at time of neuropsychological testing and later diagnosed with incident dementia; 149 nondemented individuals depressed at time of neuropsychological testing and a diagnosis of cognitively normal.
Methodology
All participants received clinical assessment of depression, were assessed to rule out prevalent dementia at time of study enrollment, completed neuropsychological testing at time of study enrollment, and were diagnosed for cognitive disorders on an annual basis.
Results
Non-demented, acutely depressed older adults who converted to dementia during the study period exhibited broadly lower cognitive performances at baseline than acutely depressed individuals who remained cognitively normal. Discriminant function analysis indicated that 2 neuropsychological tests, CERAD Recognition Memory and Trail Making B, best predicted dementia conversion.
Conclusions
Depressed older adults with cognitive deficits in the domains of memory and executive functions during acute depression are at higher risk for developing dementia. Some cases of late-life depression may reflect a prodrome of dementia in which clinical manifestation of mood changes may co-occur with emerging cognitive deficits.
doi:10.1016/j.jagp.2012.12.009
PMCID: PMC3376682  PMID: 23395197
geriatric depression; dementia; neuropsychology; memory; executive function
11.  The Impact of Skills Training on Cognitive Functioning in Older People with Serious Mental Illness: Results from a Randomized Controlled Trial 
Objectives
Research on psychosocial interventions for people with serious mental illness (SMI) demonstrates that cognitive functioning is associated with psychosocial functioning. However, cognitive impairment is more pronounced and progressive in older adults with SMI and is associated with poorer functioning. Little is known about the long-term impact of psychosocial skills training on cognitive functioning in this rapidly growing group.
Design
We conducted post-hoc analyses on a previously reported randomized control trial to evaluate the relationship between cognitive and psychosocial functioning and the potential impact of psychosocial skills training on cognitive functioning over time.
Setting and Participants
The current study was conducted using a community-dwelling sample of 183 people older than age 50 with SMI.
Intervention
Half of the study sample received a psychosocial skills training and health management program, Helping Older People Experience Success (HOPES), and were compared to a Treatment as Usual (TAU) group.
Measurements
Cognitive and psychosocial functioning were assessed at baseline and at 1-, 2-, and 3-year follow-up.
Results
Psychosocial functioning was strongly related to cognitive functioning at baseline. Participation in HOPES was not associated with greater improvements in overall cognitive functioning; however, exploratory analyses suggested a modest improvement in executive functioning.
Conclusions
Given the lack of long-term data on interventions associated with sustaining or improving executive functioning in older adults with SMI, these exploratory findings suggest that future research is warranted to establish the potential benefit of psychosocial skills training as a component of treatment aimed at enhancing long-term psychosocial and cognitive functioning.
doi:10.1097/JGP.0b013e31826682dd
PMCID: PMC3529976  PMID: 23395191
schizophrenia; mood disorders; severe mental illness; neurocognitive functioning; psychosocial functioning; aging
13.  Cognition and amyloid load in Alzheimer’s imaged with florbetapir F 18 (AV-45) PET 
Objectives
We examined the association between regional brain uptake uptake of a novel amyloid PET tracer florbetapir F 18 ([18F]-AV-45) and cognitive performance in a pilot study.
Design
Cross-sectional comparison of florbetapir F 18 ([18F]-AV-45) in AD patients vs. controls.
Setting
3 specialty memory clinics
Participants
11 participants with probable Alzheimer’s disease (AD) by NINDS/ADRDA criteria and 15 healthy comparison participants (HC).
Measurements
Participants underwent PET imaging following a 370 MBq (10 mCi) i.v. administration of florbetapir F 18. Regional/cerebellar standardized uptake value ratios (SUVRs) were calculated. Cognition was assessed using Mini-Mental State Exam, Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Wechsler Logical Memory IA (immediate recall) test (LMIA), and verbal category fluency.
Results
Greater florbetapir F 18 SUVR was associated with poorer performance on all cognitive tests. In the HC group, occipital, parietal, precuneus, temporal, and cortical average SUVR was associated with greater ADAS-Cog, and greater anterior cingulate SUVR was associated with lower LMIA. Two HCs had flobetapir F 18 cortical/cerebellar SUVR > 1.5, one of whom had deficits in episodic recall and on followup met criteria for amnestic MCI.
Conclusions
Florbetapir F 18 SUVR in several brain regions was associated with worse global cognitive performance particularly in HC, suggesting its potential as a marker of preclinical AD.
doi:10.1016/j.jagp.2012.11.016
PMCID: PMC3711793  PMID: 23395194
Amyloid; Alzheimer’s; Cognition; Standardized uptake value ratios; Positron emission tomography; 18-Flourine; PET tracer
14.  Subthreshold Depression and Successful Aging in Older Women 
Objectives
Subthreshold Depression (StD) is common in older adults and is associated with poor self-rated health. However, the impact of StD on broader indicators of successful aging, such as positive psychological constructs, cognitive functioning, or quality of well-being, has not been assessed. We compared persons with scores above and below a predetermined threshold on the Center for Epidemiological Studies Scale for Depression (CESD) to non-depressed persons (ND) on measures of multiple domains associated with successful aging.
Design
Cross sectional survey-based psychological assessments.
Participants
1,979 community-dwelling older women participating in the Women’s Health Initiative study.
Measurements
ND was defined as a CESD score below 8, StD as a score between 8 and 15, and CESD Depression (CD) as a score of 16 or above. The study questionnaire consisted of multiple self-reported measures of positive psychological functioning (e.g., optimism, resilience), cognitive functioning and complaints, and quality of well-being. We also obtained a history of diagnosis, treatment, and hospitalization related to mental health problems.
Results
20.2% of women met CES-D criteria for StD and 7% for CD. Women with StD had worse self-rated successful aging, worse physical and emotional functioning, lower optimism, more negative attitudes toward aging, lower personal mastery and self-efficacy, and greater anxiety and hostility than ND women, but scored better on all these measures than women with CD. StD subjects also had higher self-reported rates of previous diagnosis, treatment, and hospitalization for mental health problems than the ND group. StD subjects with depressed mood and/or anhedonia were largely similar to those without these symptoms.
Conclusions
Mild-moderate levels of depressive symptoms that likely fall under a general category of StD were common, and were associated with worse functioning on virtually every component of successful aging that we examined. StD represents a clinical entity that may affect the longitudinal course of successful aging for large numbers of persons and is a potential target for clinical intervention.
doi:10.1097/JGP.0b013e3181b7f10e
PMCID: PMC3937985  PMID: 20224518
15.  Daily Functioning and Prefrontal Brain Morphology in Healthy and Depressed Community-Dwelling Elderly 
Objective
Self-perceived emotional vitality, intact mood, physical activity and social engagement are recognized as important indicators for lowered rates of morbidity and increased longevity in late-life, but little is known about their underlying neural substrates. This study examined relationships between self-reported levels of general functioning and the combined volume of three integrated prefrontal structures associated with self-perception and emotion.
Design
Cross-sectional
Setting
UCLA Semel Institute for Neuroscience, Los Angeles, CA
Participants
Depressed (N=43) and comparison (N=41) elderly subjects.
Measurements
Magnetic resonance images of orbitofrontal, gyrus rectus and anterior cingulate gray and white matter volumes were corrected for intracranial volume and combined across structures to form white matter and gray matter scales. Subjects completed the RAND Short-Form 36 Questionnaire, a self-report evaluation of daily functioning. Subscales used for analysis were Physical Function, Energy, and General Health, which were not correlated with depression.
Results
White matter volumes were associated with self-perceptions of Energy for healthy as well as depressed individuals, and gray matter volume was associated with General Health. This latter association was strongest among patients with late-onset of depression, i.e., onset > age 50, although it appeared in all diagnostic groups.
Conclusions
Although mild to moderate atrophy is expected in late-life, prefrontal atrophy may represent changes to neuroanatomical substrates that qualitatively modulate self-perceptions of energy and general health for both depressed and non-depressed persons.
doi:10.1097/JGP.0b013e3181794629
PMCID: PMC3938552  PMID: 18669941
limbic; prefrontal; health attitude; elderly; MRI; daily functioning; geriatric; atrophy; orbitofrontal; anterior cingulate; gyrus rectus
16.  Interpreting the Clinical Significance of Capacity Scores for Informed Consent in Alzheimer Disease Clinical Trials 
Objective
Among Alzheimer disease (AD) patients enrolled in a clinical trial, the authors assessed the ability of a standardized capacity assessment procedure to identify persons who are capable of giving their own informed consent.
Design
Cross-sectional interview.
Setting
Thirteen sites participating in a randomized and placebo controlled study of simvastatin for the treatment of mild to moderate AD.
Participants
Persons with mild to moderate AD and their study partners enrolled in the simvastatin clinical trial.
Measurements
Interviews to assess decision-making capacity using the MacArthur Competency Assessment Tool for Clinical Research (MacCAT-CR).
Results
Judges blinded to the subject’s clinical status had a high rate of agreement on patients capable of giving their own informed consent (κ = 0.73). The understanding subscale had the best receiver operator characteristic and an analysis of positive and negative predictive values over a range of hypothetical prevalences of incapacity to consent demonstrated the value of a range of understanding cut-points.
Conclusion
Among mild to moderate AD patients, enrolled in an actual clinical trial, these results suggest evidence based guidelines for using the MacCAT-CR understanding subscale to help guide judgments about whether a patient has the capacity to consent.
doi:10.1097/JGP.0b013e318172b406
PMCID: PMC3936673  PMID: 18556397
Informed consent; decision making capacity; Alzheimer disease
17.  Successful Aging: Definitions and Prediction of Longevity and Conversion to Mild Cognitive Impairment 
Objectives
To examine alternative models of defining and characterizing successful aging.
Design
A retrospective cohort study
Setting
Olmsted County, MN.
Participants
560 community-dwelling non-demented adults, aged 65 years and older.
Measurements
Three models were developed. Each model examined subtests in four cognitive domains: memory, attention/executive function, language, and visual-spatial skills. A composite domain score was generated for each of the four domains. In Model 1, a global z-score was further generated from the four cognitive domains, and subjects with mean global z-score in the top 10% were classified as “successful agers” whereas those in the remaining 90% were classified as “typical agers”. In Model 2, subjects with all 4 domain scores above the 50th percentile were classified as “successful agers.” In Model 3, a primary neuropsychological variable was selected from each domain, and subjects whose score remained above minus 1 SD compared to norms for young adults were labeled successful agers. Validation tests were conducted to determine the ability of each model to predict survival and conversion to mild cognitive impairment (MCI).
Results
Model 1 showed 65% lower mortality in successful agers compared to typical agers, and also a 25% lower conversion rate to MCI.
Conclusion
Model 1 was most strongly associated with longevity and cognitive decline; as such, it can be useful in investigating various predictors of successful aging, including plasma level, APOE genotype, and neuroimaging measurements.
doi:10.1097/JGP.0b013e3181f17ec9
PMCID: PMC3918503  PMID: 21606901
successful aging; optimal aging; longevity; cognitive decline
18.  Neuroticism, Extraversion, and Motor Function in Community-Dwelling Older Persons 
Objective
Personality traits are associated with adverse health outcomes in old age, but their association with motor function is unclear. We tested the hypothesis that neuroticism and extraversion are associated motor decline in older persons.
Design
Prospective, observational cohort study.
Setting
Retirement communities across metropolitan Chicago.
Participants
983 older persons without dementia.
Measurements
At baseline, neuroticism and extraversion were assessed and annual assessment of 18 motor measures were summarized in a composite measure.
Results
Average follow-up was 5 years. Separate linear mixed-effects models controlling for age, sex and education showed that baseline levels of neuroticism and extraversion were associated with the rate of motor decline. For each 7- point (~1SD) higher neuroticism score at baseline, the average annual rate of motor decline was more than 20% faster. This amount of motor decline was associated with a 10% increased risk of death as compared to a participant with an average neuroticism score. Each 6- point (~1SD) lower extraversion score at baseline was associated with an 8% faster rate of motor decline. This amount of motor decline was associated with about 9% increased risk of death as compared to a participant with an average extraversion score. Neuroticism and extraversion were relatively independently associated with motor decline. These associations were unchanged when controlling for depressive symptoms and current health status, but were partially attenuated when controlling for late-life cognitive and social activities.
Conclusions
Higher levels of neuroticism and lower levels of extraversion are associated with more rapid motor decline in old age.
doi:10.1016/j.jagp.2012.10.015
PMCID: PMC3406259  PMID: 23343488
Personality; Neuroticism; Extraversion; Aging; Motor Decline
19.  Cognitive performance of individuals with schizophrenia across seven decades: A study using the MATRICS Consensus Cognitive Battery 
Objectives
The objectives of this study are to determine the effect of aging, schizophrenia, and their interaction on cognitive function.
Design
Cross-sectional controlled study.
Setting
Community-living.
Participants
235 subjects with schizophrenia aged 19-79 and 333 comparison subjects aged 20-81.
Measurements
The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB).
Results
Older age was associated with poorer performance on 9 of 10 MCCB tests in both subjects with schizophrenia and comparison subjects. Subjects with schizophrenia were impaired relative to comparison subjects on each of the 10 tests. However, there was no interaction between aging and schizophrenia on any test. Essentially the same results were observed when analyzing performance on the seven MCCB cognitive domains and MCCB global composite score.
Conclusions
Consistent with other reports, schizophrenia appears to be a disorder marked by generalized cognitive dysfunction. However, the rate of cognitive decline appears to be similar to that observed in healthy comparison subjects. They do not experience acceleration in cognitive aging which supports the hypothesis that schizophrenia is a syndrome of premature aging. Longitudinal studies including very old patients are needed to confirm and extend these findings.
doi:10.1016/j.jagp.2012.10.011
PMCID: PMC3548068  PMID: 23343484
accelerated aging; cognition; life span; MATRICS; neuropsychology; old age; premature aging; schizophrenia
20.  Angiotensin Converting Enzyme Inhibitors and Alzheimer Disease in the Presence of the Apolipoprotein E4 Allele 
Objective
The effect of angiotensin converting enzyme (ACE) inhibitors on Alzheimer disease (AD) remains unclear, with conflicting results reported. We studied the interaction of the Apolipoprotein E (ApoE) genotype and ACE inhibitors on AD.
Methods
This was a cross-sectional study of homebound elderly with an AD diagnosis and documentation of medications taken. ApoE genotype was determined.
Results
A total of 355 subjects with status on ApoE alleles and cognitive diagnoses were studied. The average age (mean ± SD) of this population was 73.3 ± 8.3 years old, and 73% were female. Cross-sectionally, there was no difference in the number of AD cases between ApoE4 carriers and ApoE4 non-carriers or between ACE inhibitor users and non-users in the homebound elderly. ApoE4 carriers treated with ACE inhibitors, however, had more diagnoses of AD compared with those who did not have the treatment (28% versus 6%, p = 0.01) or ApoE4 non-carriers treated with an ACE inhibitor (28% versus 10%, p = 0.03). ACE inhibitor use was associated with AD diagnosis only in the presence of an E4 allele. Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08–140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education.
Conclusion
The effects of ACE inhibitors on AD may be different depending on ApoE genotype. A prospective study is needed to determine whether ACE inhibitor use accelerates or poorly delays AD development in ApoE4 carriers compared with ApoE4 non-carriers.
doi:10.1016/j.jagp.2012.08.017
PMCID: PMC3873370  PMID: 23567418
Alzheimer disease; Apolipoprotein E4 allele (ApoE4); angiotensin converting enzyme (ACE); ACE inhibitor
21.  Vascular Burden and Cognitive Functioning in Depressed Older Adults 
Background
Vascular burden is known to contribute to geriatric depression and cognitive impairment. The objective of our study was to evaluate the relationship between vascular burden and pattern of cognitive impairment in older adults with depression.
Methods
Ninety-four community-dwelling older adults (mean age = 70.8 years; SD = 7.63) diagnosed with major depression were recruited to participate in the tai chi complementary use study aimed to improve antidepressant response to an antidepressant medication. All participants received comprehensive evaluations of depression, apathy, and vascular risk factors, and completed a battery of cognitive measures of memory, cognitive control, verbal fluency, and attention.
Results
The severity of vascular burden was significantly correlated with depression severity and impaired performance on measures of cognitive control (i.e., inhibition/mental flexibility), and attention, but not memory or verbal fluency. Neither the severity of comorbid apathy nor medical illness burden was related to cognitive impairment.
Conclusions
Vascular burden in older depressed adults contributes to cognitive impairment, particularly in domains of attention and cognitive control. Our findings suggest that aggressive treatment of vascular risk factors may reduce risk for further cognitive decline in depressed older adults.
doi:10.1097/JGP.0b013e31822ccd64
PMCID: PMC3889859  PMID: 21857219
Cerebrovascular risk factors; cognitive impairment; geriatric depression; vascular disease
22.  Magnitude and Causes of Bias among Family Caregivers rating Alzheimer’s Disease Patients 
Objective
Family caregivers generally underestimate the health and well-being of Alzheimer’s disease (AD) patients when compared to patient self-assessments. The goals of this study were to identify caregiver, patient, and contextual factors associated with caregiver rating bias.
Methods
105 patients with AD and their family caregivers were assessed twice by trained interviewers one year apart. In separate interviews, caregivers were asked to rate the quality of life and suffering of their patient relative, and patients provided self-ratings using the same structured instruments. Multivariate cross-sectional and longitudinal analyses were used to identify predictors of caregiver-patient discrepancies.
Results
Caregivers consistently reported significantly higher levels of suffering and lower levels of quality of life than patients. Caregiver psychological well-being and health status accounted for a substantial portion of the difference in caregiver and patient ratings in both cross-sectional and longitudinal analyses. Caregiver depression and burden were consistently positively associated with the magnitude of caregiver-patient discrepancy, and caregiver health status was negatively associated with the size of the discrepancy.
Conclusions
Caregiver assessments of dementia patients may determine the type and frequency of treatment received by the patient, and caregivers’ ability to reliably detect change in patient status can play a critical role in evaluating the efficacy of therapeutic interventions and pharmacologic agents. Clinicians and researchers working with dementia patients who rely on caregiver reports of patient status should be sensitive to the health and well-being of the caregiver and recognize that caregiver assessments may be negatively biased when the caregiver’s own well-being is compromised.
doi:10.1016/j.jagp.2012.10.002
PMCID: PMC3330137  PMID: 23290199
23.  A Comparison of the E-BEHAVE-AD, NBRS and NPI in Quantifying Clinical Improvement in the Treatment of Agitation and Psychosis Associated with Dementia 
Objectives
The aim of this study is to compare the Empirical Behavioral Rating Scale (E-BEHAVE AD), Neurobehavioral Rating Scale (NBRS), and Neuropsychiatric Interview (NPI) in detecting behavioral disturbance and psychotic symptoms in dementia and characterizing changes in response to treatment.
Design
87 subjects in the randomized controlled trial “Continuation Pharmacotherapy for Agitation of Dementia” (CPAD) were included in this analysis. We compared the detection and changes over 12 weeks of both agitation and psychosis using these 3 instruments. A receiver operating characteristic (ROC) analysis was performed to compare the performance of the three instruments in detecting global improvement.
Results
The instruments were equally likely to detect agitation. The NBRS was most likely to detect psychosis. While the NPI best detected improvement in agitation, the instruments were equal for detecting improvement in psychosis. In the ROC analysis for overall clinical improvement in response to treatment, there were no differences in the areas under the correlated curves for the three instruments but they demonstrated different sensitivity and specificity at different cut-off points for target symptom reduction. The E-BEHAVE-AD performed best at a cutpoint of 30% target symptom reduction and the NBRS and NPI both performed best at 50%.
Conclusion
The E-BEHAVE-AD, NBRS, and NPI were more similar than different in characterizing symptoms but differed in detecting response to treatment. Differences in sensitivity and specificity may lead clinicians to prefer a specific instrument, depending on their goal and the expected magnitude of response to any specific intervention.
doi:10.1016/j.jagp.2012.10.013
PMCID: PMC3499650  PMID: 23290205
Alzheimer’s Disease; pharmacotherapy; clinical trials; BPSD; NPS; neuropsychiatric symptoms; dementia; agitation; psychosis; NPI; NBRS; E-BEHAVE-AD; rating scales; Behavioural Disturbance in Alzheimer’s Disease (BDAD)
24.  A Comparison of Psychosocial Outcomes in Elderly Alzheimer’s Caregivers and Non-Caregivers 
Objectives
To conduct ananalysis of the stress, coping, and mood consequences of Alzheimer’s caregiving.
Design
Cross-sectional.
Setting
Community-based study.
Participants
Sample included 125 Alzheimer’s caregivers and 60 demographically similar older adults with non-demented spouses (i.e., non-caregivers).
Measurements
We compared caregivers and non-caregivers on stress, coping, and mood outcomes. We also examined anti-depressant use within the caregiver sample. An emphasis was placed upon effect size differences, including Cohen’s d as well as more clinically meaningful effect sizes.
Results
Caregivers were significantly more likely to endorse depressive symptoms and to meet clinically significant cutoff for depression (40% for caregivers; 5% for non-caregivers). Approximately 25% of caregivers reported taking anti-depressant medication, although 69% of these continued to experience significant symptoms of depression. Caregivers also utilized fewer positive coping and greater negative coping strategies relative to non-caregivers.
Conclusions
The number of caregivers will increase dramatically over the next two decades, and caregivers will likely seek care from primary care providers. We provide an overview of the psychological issues facing caregivers so that effective screening and treatment may be recommended.
doi:10.1016/j.jagp.2012.10.001
PMCID: PMC3376679  PMID: 23290198
25.  Association of NEO personality domains and facets with presence, onset, and treatment outcomes of major depression in older adults 
Objectives
To assess the relationship of multiple domains and facets of the five factor model of personality with presence, onset, and severity of late life depression.
Design
Cross-sectional analysis of depression status, and age of onset. Retrospective analysis of baseline severity. Longitudinal analysis of severity after 3 and 12 months of psychiatric treatment. Setting: Private university-affiliated medical center in the Southeastern US.
Participants
One hundred twelve psychiatric patients with a current episode of unipolar major depression, and 104 nondepressed comparison subjects, ages 60 years and older (mean = 70, SD = 6).
Measurements
Revised NEO Personality Inventory, Diagnostic Interview Schedule, Montgomery-Åsberg Depression Rating Scale.
Results
Binary logistic regression found that depression was related to higher neuroticism (and all its facets), and to lower extraversion (and facets of assertiveness, activity, and positive emotionality), and conscientiousness (and facets of competence, order, dutifulness, and self-discipline). Multinomial logistic regression found some of these relationships held only for depression with onset before age 50 (hostility, self-consciousness, extraversion, assertiveness, positive emotions, order, and dutifulness). Linear regression found that personality was unrelated to depression severity at the beginning of treatment, but improvement after 3 months was related to lower neuroticism (and facets depressiveness and stress-vulnerability) and higher warmth and competence. Improvement after 12 months was related to lower neuroticism, depressiveness, and stress-vulnerability.
Conclusions
Specific personality facets are related with depression and treatment outcomes. Screening for certain personality traits at the start of treatment may help identify patients at risk of worse response to treatment after 3 months.
doi:10.1016/j.jagp.2012.11.012
PMCID: PMC3382026  PMID: 23290206
Personality; depression; neuroticism; extraversion; conscientiousness

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