Modeling Reserve as Residual Cognition
Evidence That Lifetime Cognitive Activities
Mediate the Reserve-Building Effects of
Education
Maritza Dowling, Dan Mungas, Bruce
Reed, Joshua Sonnen, Milton Strauss,
Sarah Tomaszewski Farias
UC Davis Alzheimer’s Disease Center
Advanced Psychometrics Workshop 2009
Background
• Brain pathology diminishes cognitive
performance; effects are highly variable across
individuals
• Cognitive reserve is often used to explain the
imperfect correlation between brain pathology and
clinical status
• It is a hypothetical construct
• Proxy variables, especially education, are often
used in studies of cognitive reserve
Advanced Psychometrics Workshop 2009
Approach
• Conceptually, reserve explains deviations from the
level of cognitive performance that would be
expected for a given amount of brain pathology
 High reserve = better than expected
performance
• We modeled reserve as residual cognition after
accounting for neuropathology
Advanced Psychometrics Workshop 2009
Conceptual Illustration of Approach
Npath 1
Npath 2
Npath 3
‘reserve’
Cognitive
factor
Test 1
Test 2
Test 3
Test 4
Residual
Test 5
Test 6
Advanced Psychometrics Workshop 2009
Data Sources
• 701 Neuropathology cases
 Rush Memory Assessment Project (MAP) (n=272)
 Rush Religious Orders Study (ROS)(n=429)
• All cases had comparable annual neuropsychological
assessments
• Potential Reserve Indicators: leisure time cognitive
activity (MAP), education, lifetime SES
Advanced Psychometrics Workshop 2009
Model-building Steps
paper #1, paper #2
• CFA of AD neuropathology
• CFA of cognitive measures
• Regression of cognitive domains (factors) on
neuropathology (AD, VD, LBD)
• Capture residual cognition in latent variables
• Examine dimension structure of residuals across domains;
create a second order reserve factor
• Examine independent predictors of reserve
Advanced Psychometrics Workshop 2009
A Model to Study the Determinants of Cognitive Reserve
NP Cts Inferior
Parietal Rgion
NT Cts Inferior
Parietal Region
NT Cts Mid
Frontal Brain
NT Cts
Entorhinal
Cortex
NT Cts Mid
Temporal
DP Cts Inferior
Parietal Rgion
NP Cts
Entorhinal
Cortex
NP Cts Mid
Temporal
NT Cts CA1
Hippocampal
NP Cts CA1
Hippocampal
NP Cts Mid
Frontal Brain
0
Neuritic
Plaque Cts
0
Episodic Memory
Story
Delay
Recall
1
EpisR
East Boston
Delay
Semantic Memory
Reading
SemR
Boston
Naming
Brain
Weight
Brain
Weight
1
Fluency
FluenR
Working Memory
Digits
Forward
Fruits
East Boston
Story
Digits
Backwards
Word List
Word List
Recall
Residual
Composite
LfSES
Education
1
WmR
Strokes
Lewy Bodies
0
Perceptual
Organization
1
PorgR
Perceptual
Speed
1
Symbol
Digit
Line
Orientation
Progr
Matrices
Digit
Ordering
Cognitive
Activities Age 40
Microinfarcts
0
0
Animals
Height
Diffuse
Plaque Cts
0
1
DP Cts
Entorhinal
Cortex
DP Cts CA1
Hippocampal
DP Cts Mid
Frontal Brain
Neurofibrillary
Tangle Cts II
Neurofibrillary
Tangle Cts I
DP Cts Mid
Temporal
Sex
Number
Comparison
PspR
episR
semR
wmR
ResComp
pspR
.11
Educ
porgR
flR
Advanced Psychometrics Workshop 2009
episR
.28
semR
.29
.35
wmR
ResComp
pspR
porgR
CogActBL
CogAct40
-.20
.11
Educ
LifeSES
flR
Advanced Psychometrics Workshop 2009
Summary
• It is possible to operationally define reserve as residual
cognition using latent variable modeling
• The 6 domain-specific measures of reserve were represented
well by one global reserve construct.
• Results consistent with previous studies from the Rush MAP
showing that that have used cognitive activity as a proxy
indicator of reserve
• Unaware of any studies that examine how including
cognitive activities modifies the effect of education on
incident dementia or cognitive decline
Advanced Psychometrics Workshop 2009
• Prior papers suggest cognitive activities are particularly important
markers of reserve, e.g.
 Wilson 2002: Education effect becomes ns when CA are in model
 Verghese 2003; Education and occupation effects are much
weaker when CA are in model
 Valenzuela 2005 review: Effect sizes in studies of CA on incident
dementia are stronger than effects sizes of education or occupation.
• Results are novel in showing that education is not positively related to
reserve independent of cognitive activity
 Unaware of any papers that have shown this reversal in the
directionality of effect
• Operationally defining reserve as residual cognition is a useful
approach
Advanced Psychometrics Workshop 2009
Next steps
• More background investigation on reversal of
education effect--would any further analyses
clarify what is going on?
• Otherwise, no more analysis needed
• Draft Paper Quickly
Advanced Psychometrics Workshop 2009