National Institute on Aging (NIA) IMbedded Pragmatic Alzheimer’s Disease (AD) and AD-Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory (NIA U54AG063546) THE AHRQ AND LANCET REPORTS ON DEMENTIA INTERVENTIONS: INTERPRETATION AND IMPLICATIONS FOR EMBEDDED PRAGMATIC TRIALS Presented by: Eric B. Larson, MD, MPH (Lancet Report); Joseph E. Gaugler, PhD (AHRQ Report); & Lis Nielsen, PhD (NIA)
Housekeeping • All participants will be muted • Enter all questions in the Zoom Q&A or chat box and send to All Panelists and Attendees • Moderator will curate questions and ask them at the end • Want to continue the discussion? Look for the associated podcast released about 2 weeks after Grand Rounds. • Visit impactcollaboratory.org • Follow us on Twitter: @IMPACTcollab1 • LinkedIn: https://www.linkedin.com/company/65346172 @IMPACT Collaboratory
Eric B. Larson, MD, MPH Kaiser Permanente Washington Health Research Institute Senior Investigator Former executive director of Kaiser Permanente Washington Health Research Institute and former vice president for research and health care innovation of Kaiser Permanente Washington Core Leader, IMPACT Health Care Systems Core Member, IMPACT Steering Committee
The Lancet Commission Dementia Report 2020: Perspectives and opportunities to improve care and evidence-base
Overall Lancet Summary • Well-being is the goal for much of dementia care. • Interventions should be individualized to whole person and carers. • Evidence supports psychosocial interventions “tailored” to neuropsychiatric symptoms. • Interventions for carers reduce depression and anxiety & may be cost-effective. • Keeping people with dementia physically healthy affects cognition. • Hospitalizations are distressing with poor outcomes and high costs.
Lancet 2020 Approach • Identify evidence for advances with likely greatest impact since 2017 report • “Triangulation framework”—consistency of evidence from different research lines • Summarize best evidence using quality systematic reviews, meta-analyses, or individual studies • Perform systematic literature reviews and meta-analyses where needed • “Present a synthesis of evidence …balance, strengths, and limitations”
Principles of Intervention in People with Dementia • “People with dementia have complex problems with symptoms in many domains.” • “Must consider person as a whole,” their context and their close carers. • “Dementia as an illness which affects cognition by definition affects the ability to organize activities and people with dementia often need help to do what they enjoy.” • “Wellbeing is one of the goals of dementia care.”
Medications • Less endorsement of cholinesterase inhibitors than 2017 report • “No longer remunerated in France …only offer a small benefit while shifting clinician’s attention from other interventions” • Abeta therapeutics, anti-tau, anti- amyloid and anti-inflammatory drugs while a current focus, “no evidence of efficacy and some evidence of worsening” • For symptoms: no new evidence for antipsychotics
Training, Exercise, and Physical Activity • Cognitive Training • Meta-analysis found small statistically significant benefit on overall cognition driven by 2 trials of virtual reality or video games with high risk of bias. • Cochrane review of 33 trials (2000 participants – high or uncertain risk of bias): Small to moderate effects on overall cognition lasting a few months to 1 year; “no evidence…that cognitive training was better than cognitive stimulation therapy.” • Exercise and Physical Activity • Dementia and physical activity RCT: Improved fitness but didn’t slow decline. • Reducing Disability in Dementia Study (RDAD): Increased physical activity days.
Interventions for Neuropsychiatric Symptoms of Dementia • “First line assessment and management of neuropsychiatric symptoms should focus on basic health: Describe and diagnose symptoms, look for causes such as pain…illness, discomfort, hunger, loneliness, boredom, lack of intimacy and worry that could cause the behaviours and alleviate these while considering risks of harm.” • “Evidence is slowly accumulating for the effectiveness, at least in the short term, of person centered, evidence based psychosocial interventions”
Examples: Interventions for Neuropsychiatric Symptoms of Dementia • German cluster 6-month RCT of nurse-delivered care management using a computer assisted assessment to personalize intervention modules: • Better outcomes vs. usual care on NPI scores**; greater than expected, but effects on quality of life apparent only in persons living with carer. • An 8-session home-based tailored activity program RCT (to PLWD and family member) • Reduction in overall neuropsychiatric symptoms, functional independence and pain; not sustained at 4 months.
Agitation – Evidence Growing • Distressing symptom for PLWD (contributes to costs) • Two new cluster RCTs multi-component interdisciplinary interventions in “care homes” showed reduced agitation • WHELD study: To improve communication with PLWD w/social sensory experiences or other activities; antipsychotic review and addressed physical problems; lower CMAI scores • TIME study: Manual based assessment and structured case conferences for tailored plan. Reduced agitation at 8 weeks and 12 weeks • Another 6-session RCT didn’t reduce agitation but was cost-effective, improving QOL • Conclusion: Evidence favors multicomponent interventions in care homes. Major knowledge gap: People living at home. Effect sizes as good or better than antipsychotics and no side effects.
Apathy • A new area for me – the opposite of engagement; reduced initiative and activity. • Conclusions: People engage more in preferred activities – but require additional support to do so (e.g., pleasant events). • A study in care homes: Engagement does occur in people during activities in those who attended. • Cochrane review of methylphenidate: Small improvement, low quality evidence but not on NPI apathy scale.
Carers and Carer Distress • Carer distress associated with increased use and costs of health services. • 6-year follow-up of 8 session STrAtegies for RelaTives intervention (START): A manual-based coping intervention delivered by supervised psychology graduates found continuing effectiveness for depression, risk of “case-level depression”, and 3 times lower costs c/w those not receiving intervention. • Caregiver depression rather than symptoms of PLWD associated with ED use for PLWD.
Functioning • U.K. RCT of 14 sessions of cognitive rehab focused on individual goal attainment (home-based with OT/nurse) reported increased goal attainment at 3 & 9 months, but no improvement in QOL, mood, self efficacy, cognition, carer stress, health status; and was not cost-effective. • Meta-analysis: “All interventions which had improved functioning in PLWD in the community have been individual rather than group interventions.” • Physiotherapists for exercise (2 studies) • Individualized cognitive rehab (2 studies) • In home activities focused OT (3 studies): “Reduced functional decline compared to controls
Depression and Sleep • Depression: Two new systematic reviews of antidepressants reported moderate-quality evidence that antidepressant treatment for PLWD does not lead to better control of symptomatology. • Sleep: No evidence that medication for sleep in dementia is effective and considerable evidence for harm (earlier death, increased hospitalization and falls) • “Testing of non-pharmacological interventions is ongoing”
People with Dementia Have Other Illnesses • 70-80% of those diagnosed in primary care have at least 2 other chronic illnesses; Multimorbidity is associated with faster functional decline, worse QOL for PLWD and their family carers • Hospitalization is 1.4-4 times more common c/w similar illnesses; systematic review and meta-analysis (included 34 studies, 277432 people) showed “admissions often for conditions that might be manageable in the community” • Early detection of physical illness (pain, falls, diabetes incontinence and sensory impairment) is important • No intervention has successfully reduced number of hospital admissions of community dwelling PLWD (c/w interventions like education, exercise, rehab and telemedicine which have reduced admissions for PLW/OD)
Delirium and Dementia/Physical Illness and Frailty • Co-occurrence common, especially in those over 80 years • Delirium associated with dramatic increase in risk. • Most research on delirium prevention has been in people w/o dementia. • But Hospital Elder Life Program (HELP), a delirium-prevention program, reduced incidence and includes those cognitively impaired. • No definitive evidence that any medication improves delirium. Cholinesterase inhibitors, antipsychotics and sedating benzodiazepines are ineffective and the latter are associated with mortality and morbidity. • MIGHT prevention and advances in delirium management “offer a means of dementia prevention”? • Likewise, given the link of very old age, frailty, dementia, MIGHT therapy focusing on age- related process that underpin many diseases of late life reduce the incidence and severity of dementia?
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