INTRODUCTION: Previous research has identified modifiable risk factors for Alzheimers disease (AD) in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI), which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups. METHOD: Trained interviewers conducted daily telephone surveys (Gallup-Healthways) of a representative community sample of 18,614 U.S. respondents, including 4,425 younger (age 18 to 39 years), 6,365 middle-aged (40 to 59 years), and 7,824 older (60 to 99 years) adults. The surveyors collected data on demographics, lifestyles, and medical information. Less education, smoking, hypertension, diabetes, less exercise, obesity and depression, and interactions among them, were examined for associations with SMI. Weighted logistic regressions and chi-square tests were used to calculate odds ratios and confidence intervals for SMI with each risk factor and pairwise interactions across age groups. RESULTS: Depression, less education, less exercise, and hypertension were significantly associated with SMI in all three age groups. Several interactions between risk factors were significant in younger and middle-aged adults and influenced their associations with SMI. Frequency of SMI increased with age and number of risk factors. Odds of having SMI increased significantly with just having one risk factor. CONCLUSIONS: These results indicate that modifiable risk factors for AD are also associated with SMI, suggesting that these relationships occur in a broad range of ages and may be targeted to mitigate further memory problems. Whether modifying these risk factors reduces SMI and the eventual incidence of AD and other dementias later in life remains to be determined.

Dementia is a chronic disease that requires medical and social services to provide high-quality care and prevent complications. As a result of time constraints in practice, lack of systems-based approaches, and poor integration of community-based organizations (CBOs), the quality of care for dementia is poorer than that for other diseases that affect older persons. The University of California at Los Angeles (UCLA) Alzheimers and Dementia Care (UCLA ADC) program partners with CBOs to provide comprehensive, coordinated, patient-centered care for individuals with Alzheimers disease and other dementias. The goals of the program are to maximize function, independence, and dignity; minimize caregiver strain and burnout; and reduce unnecessary costs. The UCLA ADC program consists of five core components: recruitment and a dementia registry, structured needs assessments of individuals in the registry and their caregivers, creation and implementation of individualized dementia care plans based on needs assessments and input from the primary care physicians, monitoring and revising care plans as needed, and around-the-clock access for assistance and advice. The program uses a comanagement model with a nurse practitioner Dementia Care Manager working with primary care physicians and CBOs. Based on the first 150 individuals served, the most common recommendations in the initial care plans were referrals to support groups (73%) and Alzheimers Association Safe Return (73%), caregiver training (45%), and medication adjustment (41%). The program will be evaluated on its ability to achieve the triple aim of better care for individuals, better health for populations, and lower costs.

Objectives

Depressed older adults are at risk for the development of mild cognitive impairment (MCI), but few studies have characterized MCI subtypes in geriatric depression. The objective of this study was to identify the clinical patterns of MCI in late-life depression.

Design

Baseline demographic, clinical, and neuropsychological test data collected as part of a randomized antidepressant trial for geriatric depression.

Setting

UCLA-based outpatient clinic.

Participants

One hundred thirty-eight older adults with major depression.

Measurements

A neuropsychological test battery and comprehensive evaluations of depression, apathy, quality of life, medical burden, and vascular risk factors.

Results

Seventy-one participants (51%) had MCI and 67 (49%) were cognitively normal. Of subjects with MCI, 14 (20%) had amnestic MCI and 57 (80%) had non-amnestic MCI. Overall, patients with MCI had greater depression severity, poorer quality of life, and worse performance on the Mini-Mental State Exam than patients without MCI. Patients with non-amnestic MCI had significantly greater depression severity than patients without MCI. Across all subjects, depression severity correlated with impaired performance in language and visuospatial functioning.

Conclusion

Our findings suggest that MCI is associated with greater severity of depression, poorer quality of life, and worse global cognitive function. Overall, subtypes of MCI in geriatric depression differ in the patterns of functional impairment, which may require different therapeutic approaches.

OBJECTIVE: The authors evaluated the potential of methylphenidate to improve antidepressant response to citalopram, as assessed by clinical and cognitive outcomes, in elderly depressed patients. METHOD: The authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups: methylphenidate plus placebo (N=48), citalopram plus placebo (N=48), and citalopram plus methylphenidate (N=47). The primary outcome measure was change in depression severity. Remission was defined as a score of 6 or less on the Hamilton Depression Rating Scale. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition. RESULTS: Daily doses ranged from 20 mg to 60 mg for citalopram (mean=32 mg) and from 5 mg to 40 mg for methylphenidate (mean=16 mg). All groups showed significant improvement in depression severity and in cognitive performance. However, the improvement in depression severity and the Clinical Global Impressions improvement score was more prominent in the citalopram plus methylphenidate group compared with the other two groups. Additionally, the rate of improvement in the citalopram plus methylphenidate group was significantly higher than that in the citalopram plus placebo group in the first 4 weeks of the trial. The groups did not differ in cognitive improvement or number of side effects. CONCLUSIONS: Combined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in mood and well-being, as well as a higher rate of remission, compared with either drug alone. All treatments led to an improvement in cognitive functioning, although augmentation with methylphenidate did not offer additional benefits.

Objectives

Two-thirds of individuals living with Alzheimer's disease are women. Declining estrogen levels influence mood and cognition. Cumulative lifetime estrogen exposure (CLEE) correlates with cognition later in life. We examined the relationship of CLEE to depression and cognition in older women with major depression compared to non-depressed women.

Design

Older women (age ≥60 years) with depression were compared to non-depressed women using a lifetime estrogen exposure questionnaire. CLEE was defined as combined durations of reproductive span (age of menopause minus age of menarche) and any post-menopausal hormone replacement therapy use. Higher vs lower CLEE groups were based on a median of 474 months of estrogen exposure.

Setting

University hospital outpatient research program.

Participants

135 women ≥60 years; 64 depressed and 71 non-depressed.

Measurments

Participants completed a comprehensive cognitive test battery. General linear models were used to examine the association between cognitive domain scores and CLEE in depressed and non-depressed women, controlling for age, education, and ethnicity.

Results

Depressed and non-depressed groups had significantly different levels of CLEE, measured in months: mean 495.7 (SD 108.6) vs 456.4 (SD 66.0) months, F(1,130) = 5.01, p = .03. Within the non-depressed participants, higher CLEE was associated with improved delayed recall (F(1,59) = 5.94, p = .02, effect size = .61), while no such relationship was observed in the depressed group.

Conclusion

Higher CLEE was associated with improvement in delayed recall among non-depressed, but not among depressed participants. This suggests a protective role of estrogen on memory in non-depressed older postmenopausal women. Further research should examine the role of the CLEE in antidepressant response and cognitive decline.

Purpose

Cognitive complaints are a concern for breast cancer survivors. Among various published measures for cognitive complaints, the Patient's Assessment of Own Functioning Inventory (PAOFI) is one of the few assessing a spectrum of cognitive abilities, including those most commonly reported by breast cancer survivors. This study aimed to examine the psychometric properties of the PAOFI in breast cancer survivors.

Methods

An exploratory factor analysis was conducted with a sample of breast cancer survivors (n = 189) who had completed all primary cancer treatments. Construct validity was examined by correlating factor scores with valid measures of cognitive complaints, fatigue, and quality of life. Reliability was measured by internal consistency of the items in each factor within this sample, a separate sample of breast cancer survivors with high persistent cognitive complaints (n = 72), and healthy controls (n = 63). Factor scores were compared across the three samples.

Results

A five-factor structure similar to the PAOFI standardization study was found, with factors related to executive functioning (accounting for most of the variance), two aspects of memory functioning, language, and motor/sensory-perceptual abilities. Factor scores highly correlated with measures of cognitive complaints, fatigue, and quality of life. Executive functioning and memory-related factors achieved adequate reliability across samples. Scores were significantly different across the three samples as expected.

Conclusions

The PAOFI is a reliable and valid tool for measuring cognitive complaints in breast cancer survivors.

Objective

Cognitive impairment associated with late-life depression can persist after remission of mood symptoms. Apathy, a common symptom of late-life depression, often leads to worse clinical outcomes. We examined if severity of apathy mediates cognitive difficulties in a cohort of older adults with major depression.

Methods

One hundred thirty-eight older adults with depression (54.4% female; mean [SD] age: 69.7 [7.4] years; mean [SD] education:15.6 [2.7] years) were recruited to participate in a treatment study, and only baseline data were analyzed. All participants received a comprehensive evaluation of depression, apathy, and cognition. We examined whether apathy mediated the relationship between depression and cognition, focusing our attention on memory and cognitive control. We then explored whether the mediation effects differed across women and men.

Results

Increased apathy was significantly associated with worse depression and lower performance in the cognitive control domain but not in memory. Higher depressive scores were significantly associated with worse cognitive control but not memory. Mediation analyses revealed a significant indirect effect on cognitive control by depression through increased apathy scores with the mediator accounting for 21% of the total effect. Stratifying by sex, we found that women exhibited a significant indirect effect, with the mediator accounting for 47% of the total effect, whereas there was no mediation by apathy in men.

Conclusions

The findings imply that increased apathy mediates the relationship between cognition and depression. The identification of mediating effects may inform future treatment strategies and preventive interventions that can focus on decreasing apathy to improve cognition in late-life depression.

Objective

The authors evaluated the potential of methylphenidate to improve antidepressant response to citalopram, as assessed by clinical and cognitive outcomes, in elderly depressed patients.

Method

The authors conducted a 16-week randomized double-blind placebo-controlled trial for geriatric depression in 143 older outpatients diagnosed with major depression comparing treatment response in three treatment groups: methylphenidate plus placebo (N=48), citalopram plus placebo (N=48), and citalopram plus methylphenidate (N=47). The primary outcome measure was change in depression severity. Remission was defined as a score of 6 or less on the Hamilton Depression Rating Scale. Secondary outcomes included measures of anxiety, apathy, quality of life, and cognition.

Results

Daily doses ranged from 20 mg to 60 mg for citalopram (mean=32 mg) and from 5 mg to 40 mg for methylphenidate (mean=16 mg). All groups showed significant improvement in depression severity and in cognitive performance. However, the improvement in depression severity and the Clinical Global Impressions improvement score was more prominent in the citalopram plus methylphenidate group compared with the other two groups. Additionally, the rate of improvement in the citalopram plus methylphenidate group was significantly higher than that in the citalopram plus placebo group in the first 4 weeks of the trial. The groups did not differ in cognitive improvement or number of side effects.

Conclusions

Combined treatment with citalopram and methylphenidate demonstrated an enhanced clinical response profile in mood and well-being, as well as a higher rate of remission, compared with either drug alone. All treatments led to an improvement in cognitive functioning, although augmentation with methylphenidate did not offer additional benefits.

Introduction

Geriatric depression is frequently accompanied by cognitive complaints and inflammation that increase risk for treatment-resistant depression and dementia. Memantine, a neuroprotective drug, can improve depression, inflammation, and help prevent cognitive decline. In our six-month clinical trial, escitalopram/memantine (ESC/MEM) improved mood and cognition compared to escitalopram/placebo treatment (ESC/PBO; NCT01902004). In this report, we examined the impact of baseline inflammation on mood and cognitive outcomes.

Materials and methods

We measured a panel of inflammatory cytokine markers using Human 38-plex magnetic cytokine/chemokine kits (EMD Millipore, HCYTMAG-60K-PX38) in 90 older adults 60 years and older with major depression enrolled in a 6-month double-blind placebo-controlled trial of escitalopram ​+ ​memantine (ESC/MEM) in depressed older adults with subjective memory complaints. Four cytokine factors were derived and linear models were estimated to examine the predictive ability of cytokine levels on treatment induced change in depression and cognition.

Results

Of the 90 randomized participants, 62 completed the 6-month follow up assessment. Both groups improved significantly on depression severity (HAM-D score), but not on cognitive outcomes at six months. Cytokine factor scores were not significantly different between ESC/MEM (n ​= ​45) and ESC/PBO (n ​= ​45) at baseline. Pro-inflammatory biomarkers at baseline predicted a decline in executive functioning in the ESC/PBO group but not in the ESC/MEM group, interaction F(1,52) ​= ​4.63, p ​= ​.04.

Discussion

In this exploratory analysis, the addition of memantine to escitalopram provided a protective effect on executive functioning in older depressed adults. Future studies are needed to replicate the association of cytokine markers to antidepressant and neuroprotective treatment-related change in cognition in geriatric depression.

Background

Geriatric depression with subjective cognitive complaints increases the risk of Alzheimer's Disease (AD). Memantine is a cognitive enhancer used to treat AD. In a 6-month double-blind randomized placebo-controlled trial of escitalopram and memantine (ESC/MEM), ESC/MEM improved cognition at 12 month in geriatric depression (NCT01902004). We now investigated structural neuroplastic changes at 3 months.

Methods

Forty-one older depressed adults (mean age=70.43, SD=7.33, 26 female) were randomized to receive ESC/MEM or ESC/PBO. Mood scores (Hamilton Depression Rating Scale, HAMD) and high-resolution structural T1-weighted images were acquired at baseline and 3 months. Freesurfer 6.0 for image processing and General Linear Models was used to examine group differences in symmetrized percent change gray matter volume (GMV) and cortical thickness, controlling for age and intracranial volume. Nonparametric tests were used to investigate group differences in mood and subcortical volume change.

Results

Among 27 completers (ESC/MEM n = 13; ESC/PBO n = 14), 62% achieved remission (HAMD≤6) with ESC/MEM and 43% with ESC/PBO (Fisher's exact p=.45). Change in HAMD did not differ between groups (F(1,23)=0.14, p=.7). GMV and thickness increased more with ESC/MEM than with ESC/PBO in the left middle and inferior temporal lobe, right medial, and lateral orbito-frontal cortex (OFC).

Limitations

included small sample size, dropout, and the lack of cognitive data at 3 months.

Conclusions

Although significant group differences in mood improvement were not observed, ESC/MEM resulted in increased GMV and cortical thickness in several brain regions compared to placebo. Larger longitudinal clinical trials can further examine the neuroprotective effect of memantine in geriatric depression.