Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.

Evaluating non-pharmacological approaches to nursing home dementia care: A protocol.

Background: The COVID-19 pandemic has underscored the daily challenges nursing home (NH) staff face caring for the residents living with Alzheimer's Disease and Related Dementias (ADRD). Non-pharmacological approaches are prioritized over off-label medication to manage the behavioral and psychological symptoms of ADRD. Yet, it is not clear how to best equip NH staff and families with the knowledge and strategies needed to provide non-pharmacological approaches to these residents. Methods: This clustered randomized trial will compare team- and problem-based approaches to non-pharmacological ADRD care. The team-based approach includes core training for all NH staff using a common language and strategies to support continuity and sustainability. The problem-based approach capitalizes on the expertise of the professional healthcare providers to target issues that arise. A convergent mixed methods design will be used to examine (a) comparative effectiveness of the two approaches on long-term NH resident outcomes and (b) whether either approach is protective against the negative consequences of COVID-19. The primary outcome is the percentage of ADRD residents with off-label antipsychotic medication use, which will be evaluated with an intent-to-treat approach. Staff and family caregiver perspectives will be explored using a multiple case study approach. Conclusion: This trial will be the first-ever evaluation of team- and problem-based approaches to ADRD care across multiple NHs and geographic regions. Results can provide health system leaders and policymakers with evidence on how to optimize ADRD training for staff in an effort to enhance ADRD care delivery.

A Systematic Review of Tools Assessing the Perspective of Caregivers of Residents With Dementia.

In collaboration with stakeholders, we conducted a systematic review of psychometric evidence for self-report tools measuring the perspective of family caregivers of nursing home residents with dementia. Our rationale for this review was based on evidence that nonpharmacological interventions can ameliorate dementia symptoms in nursing home residents. Such interventions require caregiver participation, which is influenced by perspectives. Yet, no existing tool measures the multidomain caregiver perspective. Our review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. The final sample included 42 articles describing 33 tools measuring domains of nursing home dementia care such as behavioral and psychological symptoms of dementia, resident quality of life, dementia-specific knowledge, communication, and medication use. We uncovered evidence gaps for tools measuring dementia-specific knowledge, communication, and medication use, all of which were important to our stakeholders. Future research should focus on development of psychometrically sound tools in alignment with the multidomain caregiver perspective.

Cognitive and emotional biomarkers of melancholic depression: An iSPOT-D report.

BACKGROUND: Depressed patients with melancholic features have distinct impairments in cognition and anhedonia, but it remains unknown whether these impairments can be quantified on neurocognitive biomarker tests of behavioral performance. We compared melancholic major depressive disorder (MDD) patients to non-melancholic MDD patients and controls on a neurocognitive test battery that assesses eight general and emotional cognitive domains including the hypothesized decision-making and reward-threat perception. METHODS: MDD outpatients (n=1008) were assessed using a computerized battery of tests. MDD participants met DSM-IV criteria for MDD and had a score ≥16 on the 17-item Hamilton Rating Scale for Depression. Melancholic MDD was defined using the Mini-International Neuropsychiatric Interview and a psychomotor disturbance observer-rated CORE measure score >7. Controls were age- and gender-matched with no previous DSM-IV or significant medical history. RESULTS: Melancholic participants (33.7% of the MDD sample) exhibited significantly poorer performance than controls across each domain of cognitive function and for speed of emotion identification and implicit emotion priming. Compared to the non-melancholic group, specific disturbances were seen on tests of information speed, decision speed, and reward-relevant emotional processing of happy expressions, even after co-varying for symptom severity. LIMITATIONS: Assessments were taken at only one medication-free time point. Reward was investigated using an emotional faces task. CONCLUSIONS: Melancholic MDD is distinguished by a specific neurocognitive marker profile consistent with reduced decision-making capacity under time demands and loss of reward sensitivity. This profile suggests an underlying deficit in mesolimbic-cortical circuitry for motivationally-directed behavior.

Impairment and distress patterns distinguishing the melancholic depression subtype: an iSPOT-D report.

BACKGROUND: This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and psychological features and treatment response characteristics that differentiate Major Depressive Disorder (MDD) outpatients with and without melancholic features. Reflecting the emphasis in DSM-5, we also include impairment and distress. METHODS: Participants were assessed pre-treatment on clinical features (severity, risk factors, comorbid conditions, illness course), psychological profile (personality, emotion regulation), functional capacity (social and occupational function, quality of life) and distress/coping (negativity bias, emotional resilience, social skills, satisfaction with life). Participants were randomized to sertraline, escitalopram or venlafaxine extended-release and re-assessed post-treatment at 8 weeks regarding remission, response, and change in impairment and distress. RESULTS: Patients with melancholic features (n=339; 33.7%) were distinguished clinically from non-melancholics by more severe depressive symptoms and greater exposure to abuse in childhood. Psychologically, melancholic patients were defined by introversion, and a greater use of suppression to regulate negative emotion. Melancholics also had poorer capacity for social and occupational function, and physical and psychological quality of life, along with poorer coping, reflected in less emotional resilience and capacity for social skills. Post-treatment, melancholic patients had lower remission and response, but some of this effect was due to the more severe symptoms pre-treatment. The distress/coping outcome measure of capacity for social skills remained significantly lower for melancholic participants. LIMITATIONS: Due to the cross-sectional nature of this study, causal pathways cannot be concluded. CONCLUSIONS: Findings provide new insights into a melancholic profile of reduced ability to function interpersonally or effectively deal with one׳s emotions. This distinctly poorer capacity for social skills remained post-treatment. The pre-treatment profile may account for some of the difficulty in achieving remission or response with treatment.

The international Study to Predict Optimized Treatment in Depression (iSPOT-D): outcomes from the acute phase of antidepressant treatment.

We aimed to characterize a large international cohort of outpatients with MDD within a practical trial design, in order to identify clinically useful predictors of outcomes with three common antidepressant medications in acute-phase treatment of major depressive disorder (MDD). The international Study to Predict Optimized Treatment in Depression has presently enrolled 1008 treatment-seeking outpatients (18-65 years old) at 17 sites (five countries). At pre-treatment, we characterized participants by symptoms, clinical history, functional status and comorbidity. Participants were randomized to receive escitalopram, sertraline or venlafaxine-extended release and managed by their physician following usual treatment practices. Symptoms, function, quality of life, and side-effect outcomes were assessed 8 weeks later. The relationship of anxiety to response and remission was assessed by comorbid Axis I diagnosis, presence/absence of anxiety symptoms, and dimensionally by anxiety symptom severity. The sample had moderate-to-severe symptoms, but substantial comorbidity and functional impairment. Of completers at week 8, 62.2% responded and 45.4% reached remission on the 17-item Hamilton Rating Scale for Depression; 53.3% and 37.6%, respectively on the 16-item Quick Inventory of Depressive Symptoms. Functional improvements were seen across all domains. Most participants had side effects that occurred with a frequency of 25% or less and were reported as being in the "none" to minimal/mild range for intensity and burden. Outcomes did not differ across medication groups. More severe anxiety symptoms at pre-treatment were associated with lower remission rates across all medications, independent of depressive severity, diagnostic comorbidity or side effects. Across medications, we found consistent and similar improvements in symptoms and function, and a dimensional prognostic effect of comorbid anxiety symptoms. These equivalent outcomes across treatments lay the foundation for identifying potential neurobiological and genetic predictors of treatment outcome in this sample.

Finding a biosignature for melancholic depression.

Melancholia is typified by features of psychomotor slowing, anxiety, appetite loss and sleep changes. It is usually observed in 20-30% of individuals meeting diagnostic criteria for major depressive disorder (MDD). There is currently no agreement on whether melancholic MDD represents a distinct entity defined by neurobiological as well as clinical features or, rather, a specifier for MDD. This situation is reflected in the revisions to DSM, including in the DSM-5 due for release in 2013. With this context in mind, the authors review the origins of the construct of melancholia in MDD, its theoretical grounding and the defining characteristics that arose from this research. The authors then outline the state of knowledge on the neurobiology of melancholia. This second aspect is illustrative of the National Institutes of Mental Health's research domain criteria initiative, which offers a framework for redefining constructs along neurobiological dimensions. The authors also consider the outlook for identifying a useful biosignature of melancholia.