The Residual Group
Project #1 of 3
Neuropathological Associates of
Multiple Cognitive Functions in
Two Community-Based Cohorts
of Older Adults
Members of the Residual Group
Maritza Dowling
Dan Mungas
Sarah Tomaszewski-Farias
Bruce Reed
Milton Strauss
Aim
• To use data from MAP & ROS cohorts to
examine the relationships between
cognitive domains and indices of
neuropathology commonly associated with
aging and cognitive decline.
• N=652
Main Steps
Identify the underlying factor structure of
• the battery of neuropsychological tests
used in MAP & ROS (17 tests), and
• observed measures associated with
neuropathological changes characteristic
of Alzheimer’s disease, cerebrovascular
disease, and LBD
Main Steps (Cont.)
•
Apply a Multiple Indicators Multiple
Causes (MIMIC) approach to investigate
the effect of particular neuropathological
substrates on the identified cognitive
domains
Latent Structure of the
Neuropathology Variables
Neurofibrillary Tangle Counts for
Mid-Frontal Brain
RMSEA=0.074
0.778
90 Percent C.I. (0.066, 0.082)
Neurofibrillary Tangle Counts for
Inferior-Parietal Region
Neurofibrillary Tangle Counts for
Mid-Temporal Region
0.839
Neuropathological
Factor 1
(NFT1)
CFI=0.943, TLI=0.929
0.896
0.603
Neurofibrillary Tangle Counts for
Entorhinal Cortex Region
Neurofibrillary Tangle Counts for
CA1 Hippocampal Region
Neuritic Plaque Counts for MidFrontal Brain Region
Neuritic Plaque Counts for MidTemporal Region
Neuritic Plaque Counts for InferiorParietal Region
Neuritic Plaque Counts for
Entorhinal Cortex Region
0.869
0.818
Diffuse Plaque Counts for MidTemporal Region
0.577
0.912
0.494
0.850
0.824
Diffuse Plaque Counts for CA1
Hippocampal Region
Diffuse Plaque Counts for
Entorhinal Cortex Region
Neuropathological
Factor 3
(NP)
0.434
0.762
0.745
0.909
0.874
0.896
Diffuse Plaque Counts for InferiorParietal Region
0.696
0.863
Neuritic Plaque Counts for CA1
Hippocampal Region
Diffuse Plaque Counts for MidFrontal Brain Region
Neuropathological
Factor 2
(NFT2)
SRMR=0.046
Chi-sq Value=356.452*
Degrees of Freedom=84
p-value=0.0000
Neuropathological
Factor 4
(DP)
0.571
0.659
4-Factor CFA Solution Using Combined ROS &
MAP Data (N=652)
***Adding Diffuse Plaque Counts
Vars re-coded 0-9; treated as continuous
R-SQUARE
Observed
Variable
Estimate
S.E.
Est./S.E.
MFRNPCT
MTMNPCT
IPNPCT
ENTNPCT
HIPNPCT
MFRDPCT
MTMDPCT
IPDPCT
ENTDPCT
HIPDPCT
MFRNFTCT
MTMNFTCT
IPNFTCT
ENTNFTCT
HIPNFTCT
0.744
0.832
0.722
0.680
0.580
0.826
0.763
0.803
0.434
0.326
0.605
0.802
0.705
0.755
0.670
0.027
0.019
0.028
0.028
0.032
0.021
0.025
0.023
0.036
0.039
0.049
0.036
0.042
0.049
0.049
27.920
43.310
25.569
24.444
18.063
38.624
30.105
35.283
12.062
8.477
12.343
22.180
16.856
15.270
13.574
Two-Tailed
P-Value
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
Latent Structure of the
Neurocognitive Scales
story
Modeling the Underlying Structure of the
Neuropsychological test Battery-Model # 1
CFI=0.96; TLI=0.946; RMSEA=0.068 with
90% CI=(0.060-0.075); SRMR=0.034
delay
Chi-square=373.68; df=101; p=0.00
17 scales
Six Factors
scdf
0.842
scwli
wrkmem
epis
scwlii
0.903
scebmt
scdb
scdoperf
0.819
0.827
scsdmt
scebdr
0.841
persp
scbname
scnccrtd
sem
scread
0.773
0.894
sclopair
0.793
animals
fruits
fluency
0.855
perorg
0.801
Range of correlations between
factors:0.773-0.903
scpmat
R-SQUARE
Observed
Variable
Estimate
S.E.
Est./S.E.
STORY
DELAY
SCWLI
SCWLII
SCEBMT
SCEBDR
SCBNAME
SCREAD
ANIMALS
FRUITS
SCDF
SCDB
SCDOPERF
SCSDMT
SCNCCRTD
SCLOPAIR
SCPMAT
0.740
0.711
0.787
0.669
0.703
0.673
0.824
0.474
0.816
0.834
0.544
0.704
0.761
0.922
0.715
0.514
0.668
0.023
0.026
0.022
0.035
0.029
0.027
0.036
0.050
0.020
0.020
0.041
0.026
0.033
0.020
0.027
0.046
0.048
31.604
27.222
35.409
19.309
24.021
24.665
23.125
9.444
40.728
40.829
13.361
27.238
23.120
46.174
26.653
11.280
13.981
Two-Tailed
P-Value
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
0.000
MIMIC MODEL WITH THE 6-FACTOR COGNITIVE
STRUCTURE &
THE 4-FACTOR NEUROPATH MODEL ASSUMING THE
ROLE OF COVARIATES
Two models: WITHOUT/WITH BRAIN WEIGHT (adjusted for height & gender),
MICROINFARCTS, STROKES, &
LEWY BODIES ALSO AS COVARIATES
A Multiple Indicator Multiple Independent Cause (MIMIC) Model for the
Relationship Between Neuropathology and Cognition-WITH Brain Weight
NP Cts Inferior
Parietal Rgion
NT Cts Inferior
Parietal Region
NT Cts Mid
Frontal Brain
NT Cts
Entorhinal
Cortex
NT Cts Mid
Temporal
NP Cts Mid
Temporal
NT Cts CA1
Hippocampal
NP Cts CA1
Hippocampal
NP Cts Mid
Frontal Brain
Neurofibrillary
Tangle Cts I
Story
Semantic Memory
Delay
Recall
Word List
East Boston
Story
Word List
Recall
Diffuse
Plaque Cts
Working Memory
Digits
Forward
East Boston
Delay
Boston
Naming
Reading
Animals
Fruits
Height
DP Cts CA1
Hippocampal
DP Cts Mid
Frontal Brain
Fluency
Sex
DP Cts
Entorhinal
Cortex
DP Cts Mid
Temporal
Neuritic
Plaque Cts
Neurofibrillary
Tangle Cts II
Episodic Memory
DP Cts Inferior
Parietal Rgion
NP Cts
Entorhinal
Cortex
Brain
Weight
Brain
Weight
Microinfarcts
Perceptual
Organization
Strokes
Lewy Bodies
Perceptual
Speed
Digits
Backwards
Digit
Ordering
Line
Orientation
Progr
Matrices
Symbol
Digit
Number
Comparison
Results
Cognitive Domain
EPISODIC
2
R
0.439
Increase
2.100
0.460
SEMANTIC
R2
0.344
Increase
3.300
0.377
WORKING Mem
CFI=0.946, TLI=0.934; RMSEA 0.047, CFI=0.942, TLI=0.929; RMSEA 0.046,
C.I.=(0.044, 0.051); SRMR=0.037
C.I.=(0.043, 0.049); SRMR=0.038
Without Brain Wight
With Brain Wight
ON
Neuritic Plaque Cts
Neurofrillay Tangles (3)
Neurofrillay Tangles (2)
Diffuse Plaques
Brain Wt
ON
-0.163
-0.347
-0.181
0.051
--
0.081
0.066
0.058
0.059
--
-2.004
-5.238
-3.110
0.872
--
0.045
0.000
0.002
0.383
--
-0.165
-0.332
-0.170
0.044
0.152
0.081
0.066
0.057
0.058
0.036
-2.042
-5.001
-2.966
0.762
4.222
0.041
0.000
0.003
0.446
0.000
Neuritic Plaque Cts
Neurofrillay Tangles (3)
Neurofrillay Tangles (2)
Diffuse Plaques
Brain Wt
ON
-0.041
-0.490
-0.053
0.064
--
0.096
0.098
0.064
0.076
--
-0.433
-4.998
-0.827
0.843
--
0.665
0.000
0.408
0.399
--
-0.041
-0.447
-0.045
0.055
0.183
0.091
0.082
0.062
0.071
0.039
-0.452
-5.472
-0.727
0.781
4.730
0.651
0.000
0.467
0.435
0.000
R2
0.264
Increase
Neuritic Plaque Cts
Neurofrillay Tangles (3)
4.400
Neurofrillay Tangles (2)
0.308
Diffuse Plaques
Brain Wt
PERCEPTUAL SPEED ON
-0.159
-0.364
0.031
0.064
--
0.093
0.080
0.064
0.070
--
-1.713
-4.529
0.483
0.912
--
0.087
0.000
0.629
0.362
--
-0.162
-0.331
0.046
0.056
0.212
0.092
0.072
0.062
0.068
0.041
-1.771
-4.600
0.743
0.823
5.115
0.077
0.000
0.458
0.411
0.000
R2
0.291
Increase
Neuritic Plaque Cts
Neurofrillay Tangles (3)
Neurofrillay Tangles (2)
Diffuse Plaques
Brain Wt
ON
-0.212
-0.180
-0.136
0.071
--
0.085
0.063
0.063
0.066
--
-2.487
-2.846
-2.151
1.089
--
0.013
0.004
0.032
0.276
--
-0.216
-0.162
-0.129
0.065
0.157
0.087
0.064
0.064
0.067
0.038
-2.489
-2.542
-2.014
0.977
4.110
0.013
0.011
0.044
0.329
0.000
Neuritic Plaque Cts
Neurofrillay Tangles (3)
Neurofrillay Tangles (2)
Diffuse Plaques
Brain Wt
ON
-0.230
-0.226
0.017
0.059
--
0.109
0.092
0.078
0.082
--
-2.113
-2.443
0.214
0.715
--
0.035
0.015
0.830
0.475
--
-0.234
-0.190
0.013
0.055
0.191
0.104
0.091
0.080
0.081
0.047
-2.240
-2.091
0.168
0.684
4.075
0.025
0.037
0.866
0.494
0.000
Neuritic Plaque Cts
Neurofrillay Tangles (3)
Neurofrillay Tangles (2)
Diffuse Plaques
Brain Wt
-0.172
-0.346
-0.025
0.065
--
0.086
0.070
0.065
0.065
--
-1.989
-4.946
-0.384
0.997
--
0.047
0.000
0.701
0.319
--
-0.179
-0.329
-0.010
0.060
0.167
0.089
0.069
0.065
0.066
0.037
-2.017
-4.768
-0.154
0.912
4.470
0.044
0.000
0.877
0.362
0.000
2.400
0.315
PERCEPTUAL ORG
R2
0.241
Increase
3.700
0.278
FLUENCY
R2
0.310
Increase
2.800
0.338
Continues
Cognitive Domain
EPISODIC
SEMANTIC
WORKING Mem
PERCEPTUAL SPEED
PERCEPTUAL ORG
FLUENCY
CFI=0.946, TLI=0.934; RMSEA 0.047, CFI=0.942, TLI=0.929; RMSEA 0.046,
C.I.=(0.044, 0.051); SRMR=0.037
C.I.=(0.043, 0.049); SRMR=0.038
Without Brain Wight
With Brain Wight
ON
Microinfarcts
Strokes
Lewy bodies
-0.021
-0.058
-0.112
0.039
0.012
0.018
-0.530
-4.629
-6.059
0.596
0.000
0.000
-0.012
-0.175
-0.218
0.036
0.037
0.037
-0.333
-4.721
-5.941
0.739
0.000
0.000
ON
Microinfarcts
-0.045
0.042
-1.060
0.289
-0.032
0.038
-0.845
0.398
-0.045
-0.120
0.015
0.026
-3.076
-4.620
0.002
0.000
-0.131
-0.226
0.043
0.049
-3.043
-4.609
0.002
0.000
-0.005
-0.058
-0.105
0.042
0.015
0.024
-0.129
-3.823
-4.436
0.898
0.000
0.000
0.004
-0.171
-0.201
0.038
0.043
0.044
0.106
-3.969
-4.581
0.915
0.000
0.000
-0.014
-0.063
-0.121
0.045
0.013
0.020
-0.322
-4.736
-5.941
0.748
0.000
0.000
-0.006
-0.193
-0.240
0.043
0.041
0.042
-0.134
-4.770
-5.714
0.893
0.000
0.000
-0.034
0.044
-0.760
0.447
-0.023
0.042
-0.545
0.586
-0.054
-0.129
0.018
0.027
-2.989
-4.813
0.003
0.000
-0.160
-0.250
0.051
0.049
-3.161
-5.139
0.002
0.000
-0.036
-0.062
-0.106
0.044
0.014
0.018
-0.812
-4.437
-5.762
0.417
0.000
0.000
-0.026
-0.190
-0.207
0.041
0.041
0.037
-0.638
-4.580
-5.666
0.523
0.000
0.000
Strokes
Lewy bodies
ON
Microinfarcts
Strokes
Lewy bodies
ON
Microinfarcts
Strokes
Lewy bodies
ON
Microinfarcts
Strokes
Lewy bodies
ON
Microinfarcts
Strokes
Lewy bodies
Next Steps
Finish paper for Project #1
We have a draft of the paper.
We need to work on discussion--Implications &
Conclusion