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

Friday, July 28, 2017

Printer Friendly Version in PDF Format (9 PDF pages)


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

July 28, 2017 -- Advisory Council Meeting #25

The meeting was held on Friday, January 26, 2018, in Washington, DC. The Research Subcommittee took charge of this meeting's theme, focusing on the process from targets to treatments. The Council heard speakers on the preclinical pipeline, the clinical trial pipeline, and the industry perspective. The meeting also included discussion of a driver diagram to guide the Council's future work, updates and a report from the October Care Summit, and federal workgroup updates. Material available from this meeting is listed below and is also available at

Comments and questions, or alerts to broken links, should be sent to


General Information


Presentation Slides



  • Welcome thru Clinical Care -- [Video]

  • LTSS Research -- [Video]

  • Public Comments thru Federal Workgroup Updates -- [Video]

  • Recommendations thru Adjourn -- [Video]