Research on efficacious treatments for apathy in Alzheimer’s disease has been hindered by a lack of consensus diagnosis, difficulties in measurement, and studies with small sample sizes.
In designing the Apathy in Dementia Methylphenidate Trial (ADMET), a trial to evaluate the efficacy and safety of methylphenidate for the treatment of apathy in Alzheimer’s disease, we encountered the following issues: defining and measuring apathy, distinguishing apathy and depression, determining an appropriate test treatment, selecting relevant secondary outcomes, recruiting participants, and deciding on a suitable method for treatment unmasking. ADMET is a 6-week randomized, double-masked, placebo-controlled multicenter clinical trial with two parallel treatment groups assigned in a 1:1 ratio with randomization stratified by clinical center. The recruitment goal is 60 randomized participants over 2 years. The primary outcomes are change in apathy severity as measured by the Apathy Evaluation Scale and the Alzheimer Disease Cooperative Study-Clinical Global Impression of Change.
The design decisions made for ADMET are important elements to be considered in trials assessing the safety and efficacy of medications for clinically significant apathy in Alzheimer’s disease.
Alzheimer dementia; methylphenidate; apathy; randomized trial
Depression is a treatable illness that disproportionately places older adults at increased risk for mortality.
We sought to examine whether there are patterns of course of depression severity among older primary care patients that are associated with increased risk for mortality.
DESIGN AND SETTING
Our study was a secondary analysis of data from a practice-based randomized controlled trial within 20 primary care practices in New York, New York, and Philadelphia and Pittsburgh, Pennsylvania.
The study sample consisted of 599 adults aged 60 years and older recruited from primary care settings. Participants were identified though a two-stage, age-stratified (60-74; 75+) depression screening of randomly sampled patients. Severity of depression was assessed using the 24-item Hamilton Depression Rating Scale (HDRS).
Longitudinal analysis via general curve mixture modeling was carried out to classify patterns of course of depression severity across 12 months. Vital status at 5 years was ascertained via the National Death Index Plus.
Three patterns of change in course of depression severity over 12 months were identified: (1) persistent depressive symptoms, (2) high but declining depressive symptoms, (3) low and declining depressive symptoms. After a median follow-up of 52.0 months, 114 patients had died. Patients with persistent depressive symptoms were more likely to have died compared with patients with a course of high but declining depressive symptoms (adjusted hazard ratio 2.32, 95% confidence interval (CI) [1.15, 4.69]).
Persistent depressive symptoms signaled increased risk of dying in older primary care patients, even after adjustment for potentially influential characteristics such as age, smoking status, and medical comorbidity (244 words).
Aged; Primary health care; Geriatric depression; Mortality
To determine whether individuals with mild cognitive impairment (MCI) differ from cognitively normal (NC) elders on a risk assessment task and whether participants and their study partners evaluate risk/benefit similarly.
University medical setting.
Seventy-nine participants (NC n=40; MCI n=39), 60–90 years (73±7 years; 53% female) and 64 study partners (NC n=36; MCI n=28), 38–84 years (68±10 years; 67% female).
Participants and study partners completed a risk assessment task that involved ranking from least to most risk four hypothetical vignettes for memory loss research (brain autopsy, blood draw, oral medication, neurosurgery). Participants also completed decisional capacity for research and neuropsychological protocols.
MCI participants’ risk rankings differed from NC risk rankings (p<0.001) with MCI participants ranking brain autopsy higher and an oral medication trial lower. Demographic, decisional capacity, and neuropsychological variables could not explain MCI participant performances. Participants and their study partners had comparable risk assessment performance (p-values=1.0). MCI study partners performing similar to their MCI participant counterparts but different from NC study partners (p=0.002; i.e., ranking autopsy higher and oral medication lower).
Findings suggest individuals with MCI assess risk differently than NC peers by overestimating the risk (or underestimating the benefit) of brain autopsy and underestimating the risk (or overestimating the benefit) of oral medication. Study partners display a similar pattern. These observations may be secondary to MCI participants’ (and their study partners’) personal connection to the potential benefits of an experimental medication for memory loss.
mild cognitive impairment; research ethics; research participation; study partners; research proxy
A key component of successful aging in old age is the ability to independently perform instrumental activities of daily living (IADLs). We examined the ability to perform multiple IADL tasks in relation to mild cognitive impairment (MCI) defined on purely neuropsychological grounds.
Population-based cohort in Southwestern Pennsylvania.
1,737 community-dwelling adults aged 65 years and older.
Classification of MCI based on performance with reference to norms in the cognitive domains of memory, language, attention, executive and visuospatial function. The ability to perform seven IADL tasks (travel, shopping, meal preparation, housework, taking medications, handling personal finances, and telephone use) as assessed by the Older Americans Resources and Services (OARS) scale.
Those with cognitively defined MCI were more likely to be dependent in at least one IADL task, and in each individual IADL task, than cognitively normal participants. Better memory and executive functioning were associated with lower odds of IADL dependence in MCI. Across the subtypes of MCI, those with the multiple-domain amnestic subtype were the most likely to be dependent in all IADL tasks; with better executive functioning associated with lower risk of dependence in select IADL tasks in this group.
Mild impairment in cognition is associated with difficulty performing IADL tasks at the population level. Understanding these associations may help improve prediction of the outcomes of MCI. It may also allow appropriate targeting of cognitive interventions in MCI to potentially help preserve functional independence.
cognition; mild cognitive impairment; everyday functioning; instrumental activities of daily living; epidemiology; community; population
Preparation for Future Care needs (PFC) has been hypothesized to help older adults adjust to inevitable life and health transitions and thereby decrease the likelihood of developing depression or anxiety.
190 primary care patients aged ≥65 years completed semi-structured research interviews and mail-back surveys at study intake and two years later. Interviews included the Structured Clinical Interview for DSM-IV, the Hamilton Depression Rating Scale, Clinical Anxiety Scale and a measure of PFC. Multiple regression analyses were used to determine the independent association of PFC at intake with depression and anxiety severity at two-year year follow-up.
Patients who had made more concrete plans at intake were less likely to meet criteria for depression diagnosis at follow-up. They also had lower anxiety severity scores. Patients who had avoided thinking about future care needs had greater depression symptom severity at follow-up. Findings were independent of potential confounds, including illness burden.
Failure to prepare for future care is a novel putative risk marker for depression and anxiety in older adulthood. Clinicians should be aware that the lack of care planning and frank avoidance may pose a risk for depression and anxiety older their patients. Future research should explore the mechanisms of care planning’s effects on subsequent mood.
Decision-Making; Long-term Care Planning; Depression; Anxiety; Future-Orientation; Aging; Primary Care
The field of aging and dementia is increasingly preoccupied with identification of the asymptomatic phenotype of Alzheimer disease (AD). A quick glance at historical landmarks in the field indicates that the agenda and priorities of the field have evolved over time. The initial focus of research was dementia. In the late 1980s and 1990s, dementia researchers reported that some elderly persons are neither demented nor cognitively normal. Experts coined various terms to describe the gray zone between normal cognitive aging and dementia, including mild cognitive impairment (MCI). Advances made in epidemiologic, neuroimaging, and biomarkers research emboldened the field to seriously pursue the avenue of identifying asymptomatic AD. Accurate “diagnosis” of the phenotype has also evolved over time. For example, the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Task Force is contemplating to use the terms major and minor neurocognitive disorders. The six papers published in this edition of the journal pertain to MCI which is envisaged to become a subset of minor neurocognitive disorders. These six studies have three points in common: 1) All of them are observational studies; 2) They have generated useful hypotheses or made important observations without necessarily relying on expensive biomarkers; and 3) Based on the new National Institute on Aging and the Alzheimer’s Association guidelines, all the studies addressed the symptomatic phase of AD. Questionnaire-based observational studies will continue to be useful until such a time that validated biomarkers, be it chemical or neuroimaging, become widely available and reasonably affordable.
Depression negatively affects health and well-being among older adults, but there have been no nationally representative comparisons of depression prevalence among older adults in England and the United States.
We sought to compare depressive symptoms among older adults in these countries and identify sociodemographic and clinical correlates of depression in these countries.
Design and Setting
We assessed depressive symptoms in non-Hispanic whites aged 65 and over in 2002 in two nationally representative, population-based studies: the US Health and Retirement Study (HRS) and English Longitudinal Study of Ageing (ELSA).
8,295 HRS respondents and 5,208 ELSA respondents.
Main Outcome Measures
We measured depressive symptoms using the eight-item Center for Epidemiologic Studies Depression Scale (CES-D). We determined whether depressive symptom differences between the US and England were associated with sociodemographic characteristics, chronic health conditions, and health behaviors.
Significant depressive symptoms (CES-D score ≥4) were more prevalent in English than US adults (17.6% vs. 14.6%, adjusted Wald test F(1, 1593) = 11.4, p<0.001). Adjusted rates of depressive symptoms in England were 19% higher compared to the US (OR: 1.19, 95% CI: 1.01, 1.40). US adults had higher levels of education, and net worth, but lower levels of ADL/IADL impairments, tobacco use, and cognitive impairment, which may have contributed to relatively lower levels of depressive symptoms in the US.
Older adults in the US had lower rates of depressive symptoms than their English counterparts despite having more chronic health conditions. Future cross-national studies should identify how depression treatment influences outcomes in these populations.
depression; Health and Retirement Study English Longitudinal Study of Ageing; older adults
The current study aims to examine the risk of suicide in persons diagnosed with dementia during a hospitalization and its relationship to mood disorders.
Event-history analysis using time-varying covariates.
Population-based record linkage.
All individuals aged 50+ living in Denmark (N = 2,474,767) during January 1, 1990 through December 31, 2000.
Outcome of interest is suicide. Relative risks are calculated based on person-days spent in each stratum.
A total of 18,648,875 person-years were observed during the 11-year study period. During this period, 136 persons who previously had been diagnosed with dementia died by suicide. Men and women aged 50–69 years with hospital presentations of dementia have a relative suicide risk of 8.5 (95% confidence interval: 6.3–11.3) and 10.8 (95% confidence interval: 7.4–15.7), respectively. Those who are aged 70 or older with dementia have a threefold higher risk than persons with no dementia. The time shortly after diagnosis is associated with an elevated suicide risk. The risk among persons with dementia remains significant when controlling for mood disorders. As many as 26% of the men and 14% of the women who died by suicide died within the first 3 months after being diagnosed whereas 38% of the men and 41% of the women died more than 3 years after initial dementia diagnosis.
Dementia, determined during hospitalization, was associated with an elevated risk of suicide for older adults. Preventive measures should focus on suicidal ideation after initial diagnosis but also acknowledge that suicides can occur well after a dementia diagnosis has been established.
Suicide; dementia; Alzheimer disease; old age; elderly persons; Denmark
Antipsychotic (AP) utilization has grown significantly in long-term care (LTC) settings. Although a growing literature associates AP use with higher mortality in elderly with dementia, the association of APs with hospital events is unclear. The authors examine prevalence and trends in AP use by Medicare beneficiaries residing in LTC and the association of APs and other drug use variables with hospital events and mortality.
Retrospective analysis using sequential multivariate Cox proportional hazards models.
Medicare Current Beneficiary Survey linked to Institutional Drug Administration and Minimum Data Set files.
A total of 2,363 LTC Medicare beneficiaries, 1999–2002.
Trends in LTC AP use overall and by type and duplicative use; association of AP utilization and two outcomes: hospital events and all-cause mortality.
AP use rose markedly from 1999 to 2002 (26.4%–35.9%), predominantly due to increased use of atypical agents. After controlling for sociodemographic and clinical factors, AP use is not related to hospital events (hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.82–1.63 p = 0.7951). AP use is associated with reduced mortality in unadjusted and intermediate models, but loss of significance in the final model (HR = 0.83, 95% CI = 0.69–1.00, p = 0.0537) suggests that disease and drug burden factors may confound the AP-mortality relationship.
This study provides no evidence of increased hospital events or mortality in LTC residents who use AP medications. Findings contribute to a growing body of evidence that APs, particularly atypical agents, may be associated with reduced mortality in LTC residents.
Antipsychotic medications; long-term care; medicare beneficiaries; drug trends
Cost-related medication nonadherence (CRN) was problematic for Medicare beneficiaries with depressive symptoms prior to Medicare Part D.
To estimate changes in CRN and forgoing basic needs to pay for drugs among Medicare beneficiaries with and without depressive symptoms following Part D implementation.
Design and Setting
We compared changes in outcomes between 2005 and 2006 before and after Part D with changes between 2004 and 2005 using logistic regression to control for demographic characteristics, health status, and historical trends.
The community-dwelling sample of the Medicare Current Beneficiary Survey (n=24,234).
Main Outcome Measures
Self-reports of CRN (skipping or reducing doses, not obtaining prescriptions) and spending less on basic needs to afford medicines.
The unadjusted annual prevalence of CRN among beneficiaries with depressive symptoms was 27% (2004), 27% (2005), and 24% (2006), compared to 13%, 12%, and 9% among beneficiaries without depressive symptoms. The annual prevalence of spending less on basic needs was 22% (2004), 23% (2005), and 19% (2006), compared to 8%, 9%, and 5% among beneficiaries without depressive symptoms. Controlling for historical changes and demographic characteristics, CRN did not decline among beneficiaries with depressive symptoms compared to beneficiaries without depressive symptoms (ratio of Part D changes 0.98; 95% CI, 0.73-1.32). Respondents with depressive symptoms appeared less likely to spend less on basic needs compared to individuals without depressive symptoms (0.70; 95% CI, 0.49, 1.01), however this difference was not statistically significant.
Despite a Medicare Part D goal to improve medication adherence among mentally ill beneficiaries, the disparity in economic access to medications between beneficiaries with and without depressive symptoms did not improve after the start of Part D.
depression; Medicare Part D; cost-related nonadherence to medications
Ethical guidelines suggest that, when enrolling dementia patients in research, alterative decisionmakers (proxies) should base their decision on a “substituted judgment” of how the patient would have decided. If unable to make a substituted judgment, proxies are asked to decide based on the patient’s best interests. This mixed-methods study is the first to examine explicitly whether and to what degree proxies differentiate between these two approaches, and what considerations influence their mode of decisionmaking.
Interview study regarding enrollment of relative in hypothetical clinical trial of an investigational drug for Alzheimer’s disease (AD). Participants were randomized to respond to questions about one of four hypothetical clinical trials that differed by levels of described risk and potential benefit.
Proxy decisionmakers (n=40).
Open-ended and rating-scaled items.
Half of the proxies agreed with both of two rating-scaled items asking about different approaches to decisionmaking—i.e., agreeing that they would decide based on how their relative would have decided, and agreeing that they would decide based on what they believed was in their relative’s best interests. Narrative responses elaborated on themes within the following three major domains: Substituted Judgment, Best Interests, and Weighing Substituted Judgment and Best Interests. Substituted Judgment was framed as honoring the patient’s wishes and values. Best Interests was described as a perceived duty to maintain quality of life and avoid burdens or risks. Weighing the two standards emerged as a challenging, yet important, way of honoring wishes while maintaining quality of life. An unexpected theme was the attempt by alternative decisionmakers to discern their loved one’s current, vs. premorbid, research preferences.
Tensions exist between abstract ethical principles regarding decisionmaking “standards” and their translation into research decisions.
To explore the neuropsychological correlates of the capacity to consent to research and to appoint a research proxy among persons with Alzheimer’s disease.
Design, Setting, and Participants
Interview study of 77 persons with Alzheimer’s disease recruited through an Alzheimer’s disease research center and a memory disorder clinic.
The capacity to consent to two research scenarios (a drug randomized clinical trial and a neurosurgical clinical trial) and the capacity to appoint a research proxy were determined by five experienced consultation psychiatrists who rendered categorical judgments based on videotaped interviews of the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and the Capacity to Appoint a Proxy Assessment (CAPA). Mattis Dementia Rating Scale-2 (DRS-2) was used to assess neuropsychological functioning.
The capacity to appoint a proxy and to consent to the drug randomized clinical trial, as determined by a majority or greater opinion of the 5-psychiatrist panel, were predicted by Conceptualization and Initiation/Perseveration subscales whereas the capacity to consent to a neurosurgical randomized clinical trial was predicted by the Memory subscale. Furthermore, the more lenient individual psychiatrists’ judgments were predicted by the Conceptualization subscale whereas the stricter psychiatrists’ judgments were predicted by the Memory subscale.
How experienced psychiatrists view Alzheimer’s patients’ capacity for consenting to research and for appointing a proxy may be related to the patients’ conceptualization and memory functioning. More explicit and standardized guidance on the role of short term memory in capacity determinations may be useful.
decision-making capacity; neuropsychology; Alzheimer’s disease
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.
Longitudinal, with mean follow-up of 5.45 years.
Outpatient depression treatment study at Duke University
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.
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.
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.
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.
geriatric depression; dementia; neuropsychology; memory; executive function
Geriatric depression is associated with frontolimbic functional deficits, and this frontal dysfunction may underlie the marked executive control deficits often seen in this population. Our goal was to assess the integrity of frontal cortical functioning in geriatric depression while these individuals performed a standard cognitive control task. The N2 component of the event-related potential (ERP), an evoked response generated within the anterior cingulate cortex (ACC), is significantly enhanced when non-depressed individuals successfully inhibit a response, providing an excellent metric of frontal inhibitory function.
We used a variant of a demanding Go/NoGo task-switching paradigm that required participants to inhibit response execution during NoGo trials by overcoming a potent response tendency established by frequent Go trials.
We compared a cohort of depressed geriatric outpatients (n=11) with a similarly aged group of non-depressed participants (n=11).
Reaction times, accuracy and high-density ERP recordings from a 64-channel electrode montage were obtained.
A significantly enhanced N2 to NoGo trials was observed in non-depressed elderly participants, with generators localized to the ACC. In contrast, this enhancement was strongly reduced in the depressed sample. Source-analysis and topographic mapping pointed to a displacement of N2 generators towards more posterior areas of the middle frontal gyrus in depressed subjects.
Findings confirm previous reports of an inhibitory control deficit in depressed elderly who show significantly increased rates of commission errors (i.e., failures to inhibit responses on NoGo trials). Electrophysiological data suggest underlying dysfunction in ACC as the basis for this deficit.
Aging; Geriatric; Elderly; Depression; N2 component; ERP; Executive control; Anterior Cingulate Cortex; ACC; EEG; Response Inhibition
To conduct ananalysis of the stress, coping, and mood consequences of Alzheimer’s caregiving.
Sample included 125 Alzheimer’s caregivers and 60 demographically similar older adults with non-demented spouses (i.e., non-caregivers).
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.
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.
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.
In clinically anxious individuals, selective attention to negative cues in the environment may perpetuate a vicious cycle of emotional dysfunction. However, very little is known regarding the role of negative attentional bias in anxious older adults. There is evidence that in older adults without clinical anxiety, the opposite bias (toward positive, and away from negative, emotional material) is present. We explored how these age-related changes in emotional processing interact with anxiety.
Sixty older adults (age 60+) completed the emotional Stroop (eStroop) task, a widely used measure of attentional bias which requires rapid identification of the color in which neutral and emotional words are printed. Participants were stratified into high-, mid-, and low-worry groups on the basis of a self-report measure, the Penn State Worry Questionnaire.
The high-worry group exhibited a bias towards threat-related words, while the low- and mid-worry groups showed a bias away from threat-related words. By contrast, the low- and mid-worry groups showed a bias towards positive words, potentially consistent with an established positivity effect in older adults; while the high-worry group showed a bias away from positive items.
Older adults who worry frequently exhibit a pattern of eStroop performance that is broadly consistent with the younger adult literature, suggesting that selective attention towards threat-related information may be seen as a relevant factor in older, as in younger, anxiety.
aging; attention; generalized anxiety; emotional Stroop
To evaluate the effects of a behavioral intervention, Tai Chi Chih (TCC) on circulating markers of inflammation in older adults.
A prospective, randomized, controlled trial with allocation to two arms, TCC and health education (HE), 16 weeks of intervention administration, and 9 weeks follow-up.
A total of 83 healthy older adults, aged 59 to 86 years.
The primary endpoint was circulating levels of interleukin 6 (IL-6). Secondary outcomes were circulating levels of C-reactive protein (CRP), soluble IL-1 receptor antagonist (sIL-1RA), sIL-6R, soluble intercellular adhesion molecule (sICAM) and IL-18. Severity of depressive symptoms, sleep quality, and physical activity was also assessed over the treatment trial.
Among those older adults with high levels IL-6 at entry, a trend for a treatment group by time interaction was found (F(1,70)=3.48, P = .07), in which TCC produced a drop of IL-6 levels comparable to those found in TCC and HE subgroups who had low levels of IL-6 at entry (t’s(72)=0.80, 1.63, P’s>0.10), whereas IL-6 in HE remained higher than the TCC- and HE subgroups with low entry IL-6 (t(72)=2.47, P=0.02; t(72)=1.71, P=0.09). Decreases in depressive symptoms in the two treatment groups correlated with decreases of IL-6 (r=.28, P <.05). None of the other cellular markers of inflammation changed in TCC vs. HE.
TCC can be considered a useful behavioral intervention to reduce circulating levels of IL-6 in older adults who show elevated levels of this inflammatory marker and are at risk for inflammation-related morbidity.
Tai Chi; Inflammation; Stress; Aging
The current study explored the value of visuospatial findings for predicting the occurrence of visual hallucinations (VH) in a sample of patients with Dementia with Lewy bodies (DLB) compared to patients with Alzheimer’s disease (AD).
Retrospective analysis of 55 autopsy-confirmed DLB and 55 demographically-similar, autopsy-confirmed AD cases determined whether severe initial visuospatial deficits on the WISC-R Block Design subtest predicted the development of VH. Visuospatial deficits were considered severe if Block Design z-scores were 2.5 or more standard deviations below the mean of a well-characterized normal control group (Severe-VIS; DLB: n=35, AD: n=26) and otherwise were considered mild (Mild-VIS; DLB: n=20, AD: n=29).
Forty percent of the Severe-VIS DLB group had baseline VH compared to 0% of Mild-VIS DLB patients. Only 8% of the Severe-VIS and 3% Mild-VIS AD patients had baseline VH. During the follow-up period (mean=5.0 years), an additional 61% of the Severe-VIS but only 11% of the Mild-VIS DLB patients developed VH. In that period, 38% of the Severe-VIS and 20% of the Mild-VIS AD patients developed VH. After considering initial MMSE score and rate of decline, logistic regression analyses found that performance on Block Design significantly predicted the presence of VH in the DLB group but not the AD group.
The presence of early, severe deficits on neuropsychological tests of visuospatial skill increases the likelihood that patients with suspected DLB will develop the prototypical DLB syndrome. The presence of such deficits may identify those DLB patients whose syndrome is driven by alpha-synuclein pathology rather than AD pathology and may inform treatment plans as well as future research.
Lewy body disease; Hallucinations, visual; Alzheimer’s disease; Visuospatial cognition
Prior studies have shown that estradiol improves mood in women around the menopause transition [1, 2] but does not improve mood for older postmenopausal women (Morrison et al. 2004). Newhouse et al.  have previously shown that estradiol treatment in non-depressed women resulted in increased negative mood after psychosocial stress. The current study examined whether age after menopause impacted the effect of estradiol on mood after a psychosocial stress manipulation. Participants were 22 postmenopausal women placed on either oral placebo or 17β-estradiol (1 mg/day for 1 month, then 2 mg/day for 2 months). At the end of the 3 month treatment phase they performed the Trier Social Stress Test (TSST) followed by mood ratings. To examine the effects of age on the estrogen-stress interaction, we performed a median split on age and created four groups of participants: younger-placebo (mean age 55.5), younger-estradiol (mean age 55.5), older-placebo (mean age 73.0), and older-estradiol (mean age 76.8). The results showed that both older and younger estradiol-treated participants exhibited a significant and similar increase in negative mood after psychosocial stress compared to placebo-treated women. These results suggest that estradiol may play a significant role in modulating emotional reactivity to stressful events and that this effect persists in older women. Furthermore, responsivity to estradiol effects on emotional processing appears to be intact even years after menopause in contrast to other cognitive and behavioral effects of estradiol which may be limited to the early postmenopausal years.
Stress; Aging; Menopause; Estrogen
This editorial provides a summary of the state of research on stress-related changes associated with aging and discuss how factors such as inflammation and sex steroid alterations may interact with psychosocial stress to affect the risk for mood and cognitive disturbance in older individuals. The authors provide an integrated summary of four studies reported in this issue of the journal and views on future direction in stress and aging research and interventions targeting resilience to stress.
Stress; aging; allostatic load; menopause; estrogen; inflammation; coping; well-being
Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults.
Observational study of community-dwelling, healthy older adults.
Participants completed the study in a clinical research laboratory of a mid-sized university.
Generally healthy, community-dwelling men and women 50 years of age and older.
IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness.
Participants categorized as poor sleepers based on Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors compared to good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness.
Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation.
sleep disturbance; stress; interleukin-6
Activation of proinflammatory cytokines is associated with depressed mood, feelings of fatigue, and changes in cognitive function. This study examined the relationships between cognitive performance and circulating cellular markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), in moderately depressed and comparison healthy elderly. We conducted a cross-sectional analysis of 87 volunteers (45 nondepressed, 42 depressed) in which participants completed the Structured Clinical Diagnostic Interview and were evaluated by a geriatric psychiatrist for dementia, depression, stroke risk and neurological disorders. Volunteers also completed an EKG, standard battery of laboratory tests and neuropsychological examination that assessed memory functions of Encoding and Recall, Executive Function and Attention/Processing. Mid-morning IL-6 and CRP levels were assessed. The data analysis showed that Encoding and Recall were inversely associated with IL-6 across diagnostic groups after controlling for chronological age, MMSE, body mass index, literacy level, depression severity and sex. CRP was not associated with cognition. Depression status was associated with recall independent of IL-6 levels. In conclusion, IL-6 serum levels among elderly individuals is a significant correlate of memory performance. Women, in particular, appear sensitive to IL-6 fluctuations across diagnostic groups.
immune system; cognition; dementia; depression; aging; cytokines; geriatric
To determine if there is a specific pattern of gross motor activity associated with apathy in individuals with Alzheimer’s disease (AD).
Examination of ad libitum 24-hr ambulatory gross motor activity patterns
92 individuals with AD, 35 of whom had apathy
Wrist actigraphy data were collected and examined using functional principal component analysis (fPCA).
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, ANOVA). 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).
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.
apathy; actigraphy; functional data analysis; circadian; sleep; Alzheimer’s disease
To describe how members of the older general public deliberate with one another in finding solutions to the dilemma of involving decisionally incapable persons in dementia research.
Design, Setting, and Participants
160 persons aged 50+ who participated in an all-day deliberative democracy (DD) session on the ethics of surrogate consent for dementia research. The DD day consisted of both extensive, interactive education with experts in clinical research and ethics, as well as small group deliberations.
Audiotaped small group deliberations were transcribed and analyzed, and the main thematic elements were coded.
During deliberation, participants acknowledged the limitations of advanced research directives and discussed ways to improve their use. Although there was consensus about the necessity of surrogate consent, the participants recognized potential pitfalls and looked for ways to safeguard the process. Participants supporting surrogate consent for research emphasized societal and individual benefit, the importance of assent, and trust in surrogates and the oversight system. Other participants felt that the high risk of some research scenarios was not sufficiently offset by benefits to patients or society.
Members of the older general public are able to make use of in-depth education and peer deliberation to provide reasoned and informed opinions on the ethical use of surrogate consent for dementia research. The public’s approach to surrogate consent is one of cautious pragmatism: an overall trust in science and future surrogates with awareness of the potential pitfalls, suggesting that their trust cannot be taken for granted.
surrogate consent; dementia; deliberative democracy