COGNITIVE TRAINING FOR PEOPLE WITH MILD TO MODERATE …

COGNITIVE TRAINING FOR PEOPLE WITH MILD TO MODERATE DEMENTIA

Alex Bahar-Fuchs, PhD

NHMRC Boosting Dementia Leadership Fellow

@AlexBaharFuchs

A SYSTEMATIC REVIEW AND META-ANALYSIS

COGNITIVE TRAINING FOR PEOPLE WITH MILD TO MODERATE DEMENTIA

Alex Bahar-Fuchs, PhD

NHMRC Boosting Dementia Leadership Fellow

ACADEMIC UNIT FOR PSYCHIATRY OF OLD AGE

1. Academic Unit for Psychiatry of Old Age, Department of Psychiatry, the University of Melbourne, Australia

2. Centre for Research on Ageing, Health, and Wellbeing, Research School of Population Health, the Australian National University, Australia

3. Joseph Sagol Neuroscience Research Centre, Sheba Medical Centre, Tel-Hashomer, Israel

Disclosures: None

Support: NHMRC/COCHRANE COLLABORATION

@AlexBaharFuchs

A SYSTEMATIC REVIEW AND META-ANALYSIS

Alex Bahar-Fuchs, NARI 2019 3

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013069.pub2/full#CD013069-sec1-0001

OUTLINE


• Cognitive training in dementia: The 2019 bottom line

• Cognitive training (CT): Conceptual challenges

• CT for people with dementia: Early synthesis efforts

• CT for people with dementia: A Cochrane Review (2001-2018)• Evolving methodology

• Key findings • From previous versions

• From the 2019 update

• Implications and summary: where to from here?



Comparison II: CT vs. Control in the medium term


Comparison III: CT vs. Alt. Tx immediately post-treatment


Comparison IV: CT vs. Alt. Tx in the medium term


Malmberg et al. 2018

COTs in older adults: An overview systematic review

CT: CONCEPTUAL CHALLENGES


• An exact definition of CT remains elusive • Core ingredients? (e.g., repeated practice,

adaptive difficulty, use of strategies)

• Nature of training (process vs. tasks vs. skills, clarity of underlying cognitive domain)

• Relevance of platform & setting (pen & paper, real-world activity, computerised, etc)

• Overlap with related approaches (cog stimulation, cog rehab)?

• CT vs. Combination treatment (e.g., ‘exergaming’)

Clare 2004

Sitzer 2006

Gates 2008

CT in dementia: Evolution of synthesis efforts


• Selective, scoping reviews (e.g., Backman L. 1992, Beck C. 1996, Camp CJ et al. 1996, de Vreese et al. 2001 • Mostly addressing the use of specific

techniques to improve memory performance

• Terminology still undifferentiated

• Systematic Reviews (Buschert et al. 2010, Hopper et al. 2013, Kallio et al. 2017)

• Meta-analyses (Sitzer 2006, Olazaran et al. 2010, Gelfand et al. 2015, Hill et al. 2017)

Backman 1992. Memory training and memory improvement in AD: Rules and exceptions

CT in dementia: Cochrane Review 2001-2019


CT in dementia: Cochrane Review 2001-2019


CT IN DEMENTIA: EVOLUTION OF METHODOLOGY


Clare 2003 Clare 2008 Bahar-Fuchs 2013 Bahar-Fuchs 2019

AMSTAR SCORE (Max 16)

6.5 6 11.5 15

Population Early stage AD, VaD, Mixed Early stage AD, VaD, Mixed Mild AD, VaD, Mixed Mild to moderate dementia

Interventions Cognitive rehabilitationCognitive training (targeting mainly memory)

Cognitive rehabilitationCognitive training

Cognitive rehabilitationCognitive training

Cognitive training

Comparisons Control (active, passive, alt. treatment);Separate comparisons for outcomes

Control (active, passive, , alt. treatment); Separate comparisons for outcomes

Control (active, passive); All outcomes in a given comparison

Control (active, passive)Alt. treatment*; All outcomes in a given comparison

Outcomes considered

PwD: Cognitive (global, domains); Meta cognition; General health; ADLs; BPSD; Social engagement; QoL; Treatment satisfaction; Informant/caregiver: Mood & wellbeing; Burden & coping; Treatment satisfaction Course of the disorder: Clinical Progression; Admission to residential care; Costs

PwD: Surrogate/Biomarker outcomes

New: Global cognition (composite)

Time point Short (immediate), Medium (up to 12 months), long term (>12 months); Assessed together

Short term (immediate) Short, Medium term (up to 12 months); Assessed separately

Short term (immediate) Medium term (up to 12 months); Assessed separately

Trial design Randomised controlled trials (parallel groups, cross-over)




Search ALOIS/Central search

Article selection In duplicate + consensus In duplicate + consensus In duplicate + consensus In duplicate + consensus

Included studies 6 (all CT, 1 CCT) 9 (all CT, 1 CCT) 12 (11 CT, 1 CR) 33

Data extraction Not specified Single reviewer Single reviewer Single reviewer

Excluded studies reported

Yes (n=17) Yes (n=26) Yes (n=51) Yes (n>70)

Risk of Bias rating* In duplicate/In text/ not including allocation concealment

Not described in Method/ In text/Did not include allocation concealment

Cochrane RoB tool V.1/Single rater + reviewer

Cochrane RoB tool V.1/two raters + consensus

Treatment effect Not specified Change from baseline; assumption of r=0

Change from baseline; assumption of r=0

Change from baseline; Both r=0 & r=0.8 assumptions tested

Unit of analysis Not specified Cross-over trials Cross-over trials; ‘no-contact’ control preferred; ‘significance’ as basis for measure selection

Cross-over trials; combined groups; pre-specified measure selection process

Ax of heterogeneity Not specified I2 I2 >40% I2 >40%

Ax of publication bias/small study effx

No No No Funnel plots




Data synthesis RevMan; Fixed effects SMD/MD

RevMan; Fixed effects SMD/MD

Fixed effects SMD/MD Random effects SMD/MD

Sub-group analyses No No No Yes (multiple)

Sensitivity analysis No No Post-treatment effects only Yes (r=0 assumption)

Grading the evidence

No No Yes; Summary of Findings Table

Yes; Summary of Findings Table/grading each outcome

Other considerations No language restrictionTwo studies included in previous version were excluded

Alex Bahar-Fuchs, NARI 201918

CT IN DEMENTIA: KEY FINDINGS FROM PREVIOUS VERSION




Cognitive training for people with dementia2019 update (Published 26.3.19)

Alex Bahar-Fuchs, Anthony Martyr, Anita Goh, Julieta Sabates, Linda Clare



• Of the 33 included studies, 10 were included in the previous review

• Included studies published between 1988-2018

• Conducted in 12 countries

• 13 trials conducted in Italy (10 since 2008!)

• No new studies from the US, UK, Canada & Australia

• Only 3 trials registered

• No published protocols

Results of the search

Risk of Bias



CT vs CONTROL: GLOBAL COGNITION IMMEDIATELY POST TREATMENT

(r=0.8)


CT vs CONTROL : GLOBAL COGNITION IMMEDIATELY POST TREATMENT

(r=0.8)


CT vs CONTROL: GLOBAL COGNITION IMMEDIATELY POST TREATMENT


CT vs CONTROL: GLOBAL COGNITION AT FOLLOW-UP

(r=0.8)


CT: EFFECTS ON GLOBAL COGNITION IMMEDIATELY POST TREATMENT: SUB-GROUPS

• Subgroup analyses conducted to evaluate the potential effects of categorical effect moderators• Type of control • Type of CT • Dose (frequency, duration)• Risk of Bias

• No significant effects of moderators on the main outcome (global cognition) found, but trends suggested:• An advantage for interventions >3 times p/w • Traditional CT over ‘augmented’ CT

• Some effect moderators were more influential in relation to other outcomes


CT vs CONTROL: ALL POST-TREATMENT OUTCOMES


CT vs CONTROL: ALL FOLLOW-UP OUTCOMES


HOW CONFIDENT ARE WE? GRADING THE EVIDENCE

• Confidence ratings using GradePro

• Completed for each outcome in each comparison • By consensus of two raters

• Grading involves downgrading evidence (1 or 2 points): • Risk of Bias (critical items)• Imprecision (N, CIs)• Inconsistency (heterogeneity)• Publication Bias (visual inspection only when

k>10)• Indirectness (relationship between findings

and review question)


SUMMARY & NEXT STEPS

• For the first time, the evidence suggests CT-related gains for global cognition in mild-moderate dementia• May be sustained over the medium term• May also apply for some specific cognitive domain

• No CT-related benefits relative to• Most non-cognitive (including functional) domains• Alternative treatments

• Quality of evidence in relation to most outcomes remains very low• Difficult to draw firm conclusions• See recently published Cochrane Reviews of CT in people with MCI,

cognitively healthy older people, middle-aged people (Gates et al. 2019)

• Comparisons with effects of approved AD medications

• Will we need to revise our thinking/guidelines? www.cogtale.org

http://www.cogtale.org/

ACKNOWLEDGEMENTS

UoM

Anita Goh

Julieta Sabates

Amit Lampit

Nicola Lautenschlager

Exeter

Linda Clare

Anthony Martyr

Ola Kudlicka

Cochrane Dementia and Cognitive Improvement Group

Sue Marcus

Jenny McCleery

Anna Noel-Storr

Candida Fenton

Peer Reviewers

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COGNITIVE TRAINING FOR PEOPLE WITH MILD TO MODERATE …