The Roles of Apathy and Depression in Predicting Alzheimer Disease: A Longitudinal Analysis in Older Adults With Mild Cognitive Impairment

ObjectiveApathy and depression have each been associated with an increased risk of conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).These symptoms often co-occur and the contribution of each to risk of AD is not clear.MethodsNational Alzheimer's Coordinating Center participants diagnosed with MCI at baseline and followed until development of AD or loss to follow-up (n = 4,932) were included. The risks of developing AD in MCI patients with neuropsychiatric symptoms (NPS) (apathy only, depression only, or both) were compared to that in those without NPS in a multivariate Cox regression survival analysis adjusting for baseline cognitive impairment, years of smoking, antidepressant use, and AD medication use.ResultsThirty-seven percent (N = 1713) of MCI patients developed AD (median follow-up 23 months). MCI patients with both apathy and depression had the greatest risk (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.17–1.61; p < 0.0001; Wald χ² = 14.70; df = 1). Those with apathy only also had a greater risk (HR = 1.24; 95% CI: 1.05–1.47; p = 0.01; Wald χ² = 6.22; df = 1), but not those with depression only (HR = 1.08; 95% CI: 0.95–1.22; p=0.25; Wald χ² = 1.30; df = 1). Post-hoc analyses suggested depression may exacerbate cognitive decline in MCI patients with apathy (odds ratio = 0.70; 95% CI 0.52–0.95; p = 0.02; Wald χ² = 5.28; df = 1), compared to those without apathy.ConclusionMCI patients with apathy alone or both apathy and depression are at a greater risk of developing AD compared to those with no NPS. Interventions targeting apathy and depression may reduce risk of AD.     

Mild Cognitive Impairment and Caregiver Burden: A 3-Year-Longitudinal Study

ObjectivesMild cognitive impairment (MCI) is common, affecting 10%–35% of people over 65, and poses unique challenges for patients and their caregivers. Comparatively little research has examined caregiver burden in this population, with longitudinal research, in particular, lacking. We examined caregiver burden in a sample of people with MCI over 3 years.DesignThree-year observational study.SettingNine memory clinics in Australia.ParticipantsOne-hundred-and-eighty-five people with MCI and their caregivers.MeasurementsMeasures of caregiver burden, cognition, function, neuropsychiatric symptoms, driving status, and medication use were completed with patients and their caregivers at regular intervals over a 3-year period.ResultsBetween 21.1% and 29.5% of caregivers reported a clinically significant level of burden over the study. Patients’ higher levels of neuropsychiatric symptoms, lower functional ability, and lack of driving ability, and caregivers’ employment were associated with greater caregiver burden over time. Caregiver burden did not increase over time when controlling for patient and caregiver characteristics.ConclusionsHigh levels of caregiver burden are present in a significant proportion of caregivers of people with MCI. Clinical characteristics of patients – including severity of neuropsychiatric symptoms and functional impairment – and the employment status of caregivers predict burden. Such characteristics may help identify caregivers at greater risk of burden to target for intervention.     

Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults

ObjectiveMild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergent neuropsychiatric symptoms (NPS) that represent an at-risk state for incident cognitive decline and dementia in people with mild cognitive impairment (MCI). We undertook a study to determine whether MBI was associated with progressive changes in neuropsychological performance in people without significant cognitive impairment.MethodsA total of 9,931 older adults enrolled in the PROTECT study who did not have MCI or dementia undertook a comprehensive neuropsychological battery measuring attention, reasoning, executive function, and working memory at baseline and 1 year. MBI was ascertained using self-administration of the Mild Behavioral Impairment Checklist at 1 year, and participants were grouped according to MBI status: No Symptoms, Intermediate NPS and MBI. All assessments were completed online, and data analyzed using mixed-effects model repeated measures analysis of covariance.ResultsA total of 949 (10%) people had MBI. These individuals had significantly worse cognitive performance at baseline and significantly greater decline over 1 year in the four composite cognitive scores measuring attentional intensity (F [2,8578] = 3.97; p = 0.019), sustained attention (F [2,8578] = 18.63; p <0.0001), attentional fluctuation (F [2,8578] = 10.13; p <0.0001) and working memory (F [2,9895] = 13.1; p <0.0001).ConclusionOur novel findings show that MBI is associated with faster decline in attention and working memory in this cognitively normal sample. MBI may be an earlier marker of neurodegenerative disease than MCI, captured at the stage of subjective cognitive decline or before, raising the possibility that MBI represents a novel target for dementia clinical trials or prevention strategies.     

The Construction and Evaluation of Executive Attention Training to Improve Selective Attention,Focused Attention,and Divided Attention for Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial

ObjectivesTo examine the immediate and long-term effects of executive attention training on selective attention, focused attention, and divided attention in older adults with mild cognitive impairment.MethodsA double-blind, multisite randomized controlled trial at five sites. Seventy participants (mean age: 78.19 ± 7.22 years) were assigned to an experimental group (executive attention training, n = 35) or an active control group (n = 35). The training duration was the same for both groups (45 minutes per session, 3 times per week, 18 sessions in total). Primary outcome measure was selective attention (Digit Span Task). Secondary outcome measures included focused attention (Stroop Color Word Test) and divided attention (Trail-Making Test Part B). Data were collected at pretest, post-test, 3-month follow-up, and 6-month follow-up.ResultsIn GEE analysis, findings indicated a significant improvement in selective attention at post-test, whereas divided attention showed significant reducing omission error at 3-month follow-up. There was no significant effect of group in focused attention associated with the executive attention training compared with active control group.ConclusionThe executive attention training significantly improved selective attention and divided attention performance. Future studies should identify transfer effects of attention training, and that can employ early screening to provide integrated attention training, and decrease its relevant risks on competency in performing daily activities, such as falling and driving.     

Cognitive Deficits in Older Adults With Psychotic Depression: A Meta-Analysis

A major depressive disorder with psychotic features, that is, psychotic depression (PD), is often accompanied by cognitive deficits, particularly in older patients. We aimed to assess to what extent various cognitive domains are affected in older patients with PD compared to those with nonpsychotic depression (NPD). Therefore, a systematic search was conducted in Medline, Embase, Web of Science, the Cumulative Index to Nursing and Allied Literature (CINAHL), Google Scholar, and Cochrane for all relevant studies. Hereafter, we conducted a meta-analysis of seven studies on cognitive deficits in older adults (55+ years), comparing patients with PD and patients with NPD. Compared to patients with NPD, those with PD not only showed a significantly poorer performance on overall cognitive function, with a Hedges’ g effect size of ?0.34 (95% confidence interval: ?0.56; ?0.12; p = 0.003), but also on nearly all separate cognitive domains, with Hedges’ g effect sizes ranging from ?0.26 to ?0.64 (all p's <0.003), of which attention was most adversely affected. Verbal fluency showed no significant effect, although this analysis may have been underpowered. The funnel plot suggested no significant publication bias (Egger test intercept: ?2.47; 95% confidence interval: ?5.50; 0.55; p = 0.09). We conclude that older patients with PD show more cognitive deficits on all cognitive domains, except for verbal fluency, compared to patients with NPD. It is crucial that clinicians and researchers take cognitive deficits into consideration in older adults with PD.     

Hearing Impairment,Loneliness, Social Isolation,and Cognitive Function: Longitudinal Analysis Using English Longitudinal Study on Ageing

ObjectiveThis study examines the relationships between hearing impairment and cognitive function among older adults, and whether that association is mediated by loneliness and social isolation.MethodsData were drawn from English Longitudinal Study of Ageing (ELSA) wave two (2004/2005) until wave seven (2014/2015). The study sample consisted of 8,199 individuals aged 50 years or older. Cognitive function was measured using episodic memory. We performed analysis using a generalized structural equation modeling (GSEM) technique.ResultsGSEM analysis shows that the direct effect of hearing impairment on episodic memory was negative and significant (β = ?0.29, p <0.001). Loneliness and social isolation mediated that effect. Hearing impairment was positively associated with loneliness (β = 0.10, p <0.001) and social isolation (β = 0.04, p <0.001). Loneliness (β = ?0.08, p <0.001) and social isolation (β = ?0.09, p = 0.001) were significantly associated with lower memory scores.ConclusionThe link between hearing impairment and episodic memory was partly mediated by loneliness and social isolation. Interventions to improve the social networks of older adults with hearing impairment are likely to be beneficial in preventing cognitive decline. Thus, the importance of maintaining social relationships among older adults, especially those with hearing impairment is highlighted.     

Mind-Body Interventions in Late-Life Mental Illnesses and Cognitive Disorders: A Narrative Review

Background

Current pharmacological treatments and psychotherapeutic approaches often have adverse effects or are ineffective in late-life cognitive and mental illnesses. Mind-body interventions offer a holistic approach and are of interest because of potential patient acceptability and scalability.

Exposure to Antidepressant Medication and the Risk of Incident Dementia

ObjectiveTo test competing hypotheses that monotherapeutic antidepressant exposure is associated with an increased versus a decreased risk of dementia.MethodsA prospective national matched cohort study from Israel (N = 71,515) without dementia (2002–2012) aged 60 and over were followed up for incident dementia from May 2013 to October 2017. Exposure to antidepressant monotherapy was classified with Anatomical Therapeutic Chemical Codes (N06A) from January 1, 2013 to December 31, 2016. The association between antidepressant monotherapy and the risk of incident dementia was quantified with hazard ratios (HR) and their 95% confidence intervals (CI) obtained from Cox regression models unadjusted and adjusted for 42 covariates. The robustness of the results was tested with 24 sensitivity analyses: 19 analyses restricted to subsamples with plausible differential dementia risks (e.g., anxiety and depression), and 5 analyses across and within antidepressant drug classes.ResultsIn the primary analysis, the risk of incident dementia for the group exposed to antidepressant monotherapy compared to the group unexposed to antidepressants was estimated with an unadjusted HR = 4.09 (df = 1, 95% Wald CI = 3.64, 4.60) and an adjusted HR = 3.43 (df = 1, 95% Wald CI = 3.04, 3.88). Across the 24 sensitivity analyses the estimated adjusted HR values ranged from 1.99 to 5.47.ConclusionIn this study, monotherapeutic antidepressant exposure in old age was associated with increased incident dementia. Clinicians, caregivers, and patients may wish to consider this potentially negative consequence of antidepressant exposure and aim to balance the costs and benefits of treatment.     

Depression Agency-Based Collaborative: Effect of Problem-Solving Therapy on Risk of Common Mental Disorders in Older Adults With Home Care Needs

BackgroundInterventions to prevent depression in older adults have mainly focused on young-old ambulatory adults, not on the old-old with disabilities who receive supportive services in their homes.ObjectiveThe Depression Agency-Based Collaborative (Dep-ABC) is a single-blind pilot randomized controlled trial assessing the effect of an intervention-development strategy using problem-solving therapy (PST) on the risk of common mental health disorders in this vulnerable population.MethodsThe intervention involved six to eight sessions of PST over 12 weeks. Participants were followed up to 12 months postintervention.ResultsDep-ABC randomized 104 participants—68.4% of eligible and 17.5% of all older adults screened. The proportion of participants with incident major depressive disorder or generalized anxiety disorder was 11.4% in PST and 14.3% in the enhanced usual care control arm. A test of the interaction between time and intervention for anxiety symptoms favored the PST arm (p = 0.04).ConclusionPST did not lower the risk of incident common mental illness but did lower anxiety symptom burden. Apart from low power, the effects of PST may have been blunted by referral for medical and aging services in the enhanced usual care group.     

The Neuropsychiatry of Parkinson Disease: A Perfect Storm

Affective disorders, cognitive decline, and psychosis have long been recognized as common in Parkinson disease (PD), and other psychiatric disorders include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their frequent occurrence, there is incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically multimorbid, and there is great intra- and interindividual variability in presentation. The hallmark neuropathophysiological changes that occur in PD, plus the association between exposure to dopaminergic medications and certain psychiatric disorders, suggest a neurobiological basis for many psychiatric symptoms, although psychological factors are involved as well. There is evidence that psychiatric disorders in PD are still under-recognized and undertreated and although psychotropic medication use is common, controlled studies demonstrating efficacy and tolerability are largely lacking. Future research on neuropsychiatric complications in PD should be oriented toward determining modifiable correlates or risk factors and establishing efficacious and well-tolerated treatment strategies.     

Weekly monitoring of dexamethasone suppression response in depression: its relationship to change of body weight and psychopathology

Weekly dexamethasone suppression tests (DST) were performed in 19 hospitalized patients with major depressive disorder, endogenous subtype, and who had an abnormal DST at admission. Depression scores (Hamilton Rating Scale) and weight changes were collected by investigators who were blind to the test results. Major findings were: (1) the DST gradually normalized 3-4 weeks prior to full resolution of clinical symptomatology; (2) weight loss was an important patient variable which may have contributed to false positive DST results; however, the positive correlation between changes in DST results and changes in depression scores in all our patients with or without weight loss suggests that psychopathological factors other than weight change participate in the development of dexamethasone resistance in depression; (3) the low dose (1 mg) version of the test requires careful control of minor medical disturbances, which can make the test result ambiguous. The data suggest that after resolution of some methodological issues the DST may serve as a valuable laboratory test to monitor clinical progress during drug treatment.