Advisory Council July 2017 Meeting Presentation: Preventing Cognitive Decline and Dementia



Friday, July 28, 2017

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Preventing Cognitive Decline and Dementia: A Way Forward

National Academies of Sciences, Engineering and Medicine

Committee on Preventing Dementia and Cognitive Impairment

  • Alan Leshner (Chair), AAAS (emeritus)
  • Story Landis (Vice Chair), NINDS (emeritus)
  • Marilyn Albert, Johns Hopkins University
  • Lisa Barnes, Rush University
  • Dan Blazer, Duke University
  • Mark Espeland, Wake Forest University
  • Taylor Harden, National Hartford Center of Gerontological Nursing Excellence
  • Claudia Kawas, UC Irvine
  • Nan Laird, Harvard University
  • Kenneth Langa, University of Michigan
  • Eric Larson, Kaiser Permanente
  • José Luchsinger, Columbia University
  • Ronald Petersen, Mayo Clinic
  • Ralph Sacco, University of Miami
  • Sudha Seshadri, Boston University
  • Leslie Snyder, University of Connecticut
  • Kristine Yaffe, UC San Francisco

The Task

  • Examine the evidence on interventions for delaying or slowing ARCD and preventing, delaying, or slowing MCI and CATD, and recommend:
    • Interventions supported by sufficient evidence to be incorporated into public health strategies and messages
    • Areas for future research

A Novel Study Model

  • Phase I: NASEM committee informs the design of an AHRQ systematic review
    • Committee met with EPC December 2015
    • AHRQ draft review released in September 2016 (final review, January 2017)
  • Phase II: NASEM Committee draws from the AHRQ systematic review and other evidence sources
    • Testimony at Oct 2016 public workshop,
    • Observational studies

Why Supplemental Sources?

  • AHRQ review focused only on RCT data
  • RCTs challenging (e.g., long follow up requirement, comorbid conditions, secular dementia trends) and, in some cases, unethical
  • Supplemental sources of evidence
    • Testimony from public workshop
    • Prospective cohort studies (intervention and risk factor studies)
    • Neurobiological studies (mechanistic and brain imaging biomarker studies)
    • Knowledge of benefits, harms, and costs

Strength of the Evidence for Interventions

  • Insufficient evidence to justify a public health information campaign to encourage adoption of specific interventions
  • Three interventions supported by encouraging, but inconclusive evidence
    • Cognitive training
    • Blood pressure management for people with hypertension
    • Increased physical activity
  • All have minimal risk of harm, and two known to be beneficial for other conditions

Cognitive Training -- Supplemental Evidence

  • No observational studies identified for cognitive training
  • Observational studies have suggested participating in cognitively stimulating activities (reading, games, learning a new language) may lower risk of cognitive impairment
  • Low educational attainment known modifiable risk factor for dementia

Cognitive Training -- Conclusions

  • Despite limitations of ACTIVE trial, moderate strength RCT evidence suggests cognitive training can delay or slow ARCD
  • No evidence that such beneficial long-term cognitive effects obtained with commercial, computer-based "brain training" applications
  • No evidence that cognitive training prevents, delays, or slows MCI and CATD

Blood Pressure Management -- Supplemental Evidence

  • Cerebrovascular disease linked to dementia, vascular component of mixed dementia increasingly recognized
  • Antihypertensives known to reduce stroke risk and subclinical cerebrovascular disease
  • Prospective cohort studies have more consistently found associations between BP lowering and improved cognitive outcomes (dementia and cognitive performance)

Blood Pressure Management -- Conclusions

  • RCT data do not offer strong support for BP management in patients with hypertension for delaying or slowing ARCD or preventing, delaying, or slowing MCI and CATD, although Syst-Eur trial provides some evidence of impact on risk of CATD
  • Add-on trials with cardiovascular primary endpoints may not have been optimally designed to detect impact on cognitive outcomes
  • Using Hill criteria, data from non-RCT studies suggest effects of BP management on incident CATD in hypertensives are consistent with a causal relationship

Recommendation 1 -- Communicating with the Public

  • NIH, CDC and other organizations should make clear that positive effects of the following interventions are supported by encouraging although inconclusive evidence:
    • cognitive training to delay or slow ARCD;
    • blood pressure management for people with hypertension to prevent, delay, or slow CATD; and
    • increased physical activity to delay or slow ARCD.

Common Methodological Limitations

  • Initiation of interventions at later life stages that may be outside optimal window for prevention
  • Inadequate follow up to assess effects of interventions on long-term clinical outcomes
  • Use of heterogeneous outcome measures and assessment tools precluded pooling results across studies
  • Failure to collect baseline data on cognition
  • Small sample sizes, underpowered studies, attrition
  • Homogeneous study populations
  • Suboptimal control groups

Recommendation 2 -- Methodological Improvements

  • NIH and other interested organizations should support studies that:
    • identify individuals at higher risk of cognitive decline and dementia and tailor interventions accordingly
    • increase participation of underrepresented populations to study intervention effectiveness in these populations
    • begin more interventions earlier with longer follow-up
    • use consistent cognitive outcome measures to enable pooling
    • integrate robust cognitive outcome measures into trials with other primary purposes
    • include biomarkers as intermediate outcomes
    • conduct large trials in broad, routine clinical practices

Recommendation 3 -- Highest Priorities for Future Research

  • NIH and other interested organizations should support further research to strengthen the evidence base on the following categories of interventions supported by encouraging but inconclusive evidence:
    • cognitive training -- e.g., components of ACTIVE trial responsible for benefits of intervention
    • blood pressure management -- e.g., optimal targets and timing
    • increased physical activity -- e.g., comparative effectiveness of different regimens

Recommendation 4 -- Additional Priorities for Future Research

  • NIH and other interested organizations should support further research to strengthen the evidence base on:
    • new antidementia treatments
    • diabetes treatment
    • depression treatment
    • dietary interventions
    • lipid-lowering treatment/statins
    • sleep quality interventions
    • social engagement interventions
    • vitamin B12 plus folic acid supplementation

Other Cross-Cutting Considerations for Research

  • Multimodal approaches -- can combining interventions improve outcomes beyond those achieved by single interventions?
  • Optimizing dose, timing, delivery schedule, and duration to maximize cognitive outcomes.
  • How can adherence to an intervention best be promoted and measured?
  • Making use of new adaptive designs for clinical trials and statistical methodologies

Final Thoughts

  • This report represents a snapshot of the state of the science in 2017 but new data constantly emerging and recommendations will need to be reassessed
  • NIA and others need to consider criteria used for public health messaging as RCTs may not always be possible or able to yield needed evidence
  • RCTs and other studies have yielded encouraging data for some interventions and public should have access to this information to inform choices
  • Committee is optimistic much more will be known on preventing ARCD and dementia in the near future

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