- Email: [email protected]
Lower cerebral blood flow is associated with cognitive decline in patients with Alzheimer’s disease
P806
Poster Presentations: P4
Ab-Ptau-pos> Ptau-pos> Ab-pos> Ab-Ptau-neg. However, a significant interaction among time, Ab and PTau levels was reported only for RD (F(1,669)¼ 5.64, p¼ .02) and MD (F(1,669)¼ 7.01, p¼ .01). Ab-Ptau-pos showed higher increased in RD relative to aMCI without neurodegeneration (Ab-Ptau-neg and Ab-pos; Tukey’s test, p<.050) and higher MD increase compared to Ab-pos (Tukey’s test, p<.05). No significant FA and L1 alterations were observed. Conclusions: These preliminary data suggest that in aMCI patients i) amyloid pathology affects in white matter diffusion only when neurodegeneration coexists and ii) RD and MD seems more sensitive than FA and L1 to detect longitudinal diffusion changes. Longitudinal analysis is still ongoing. Pharmacog is funded by the EU-FP7 for the Innovative Medicine Initiative (grant 115009).
P4-088
LOWER CEREBRAL BLOOD FLOW IS ASSOCIATED WITH COGNITIVE DECLINE IN PATIENTS WITH ALZHEIMER’S DISEASE
Marije Benedictus, Annebet Leeuwis, Joost Kuijer, Philip Scheltens, Frederik Barkhof, M. Wiesje van der Flier, Niels Prins, VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: m.benedictus@ vumc.nl Background: Cerebral blood flow (CBF) is lower in patient with Alzheimer’s disease (AD) compared to the general elderly population. We aimed to investigate whether lower CBF was associated with a more rapid cognitive decline in patients with AD. Methods: We included 88 AD patients from the Amsterdam dementia cohort, with an arterial spin labeling (ASL) scan at baseline and at least one year of clinical follow-up. 3T pseudocontinuous (PC-)ASL was used to determine whole brain and regional (parietal, frontal, occipital, temporal and cerebellar) CBF (ml/100gr/min). For statistical purposes, CBF was inverted
Table 1 Associations of CBF with baseline MMSE and annual change in MMSE Model 1 Cerebral blood flowx Whole brain Parietal Frontal Temporal Occipital Cerebellum
Estimated baseline MMSE -0.3260.39 -0.5060.41 -0.0260.43 -0.2060.39 -0.2960.38 0.2660.39
U
-0.50+0.25 -0.59+0.25* -0.1460.26 -0.4660.25 -0.47+0.25# -0.1860.26
Estimated baseline MMSE -0.2860.39 -0.45+0.41 0.1260.43 -0.17+0.39 -0.2360.39 0.3060.40
Estimated annual change in MMSE -0.49±10.25 -0.59±0.25* -0.1260.26 -0.4760.25 -0.47±0.25# -0.1760.26
P4-089
LOWER CEREBRAL BLOOD FLOW IS RELATED TO MORE SEVERE COGNITIVE IMPAIRMENT IN PATIENTS WITH DEMENTIA DUE TO ALZHEIMER’S DISEASE
Annebet Leeuwis1, Marije Benedictus1, Joost Kuijer1, Philip Scheltens1,2, Frederik Barkhof1,2, Niels Prins1, Wiesje M. van der Flier1,2, 1VU University Medical Center, Amsterdam, Netherlands; 2Neuroscience Campus Amsterdam, Amsterdam, Netherlands. Contact e-mail: [email protected] Table 1 Associations between CBF and cognitive domains in patients with mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) Mild cognitive impairment
Model 2
Estimated annual change in MMSE
(i.e., higher is worse) and standardized. Linear mixed models were used to determine associations between CBF and cognitive decline over time as measured with the MMSE. We adjusted for age, sex, education and normalized brain volume, and in a separate model additionally for white matter hyperintensities and lacunes. Results: Patients were 6567 years old, 44 (50%) were female and mean baseline MMSE was 2264. Mean follow-up of 2.160.8 years and patients declined with -2.263.0 MMSE points per year. Linear mixed models revealed no associations between whole brain or regional CBF with baseline MMSE (table 1). One standard deviation (SD) lower whole brain CBF was associated with a steeper decline of 0.5 MMSE points per year (Model 1: b[SE] -0.50[0.25], p¼0.05). In particular, lower parietal CBF was associated with steeper annual decline on the MMSE (Model 1: b[SE] -0.59[0.25], p<0.05). Lower occipital CBF tended to be associated with cognitive decline as well (Model 1: b[SE] - 0.47[0.25], p¼0.06). Additional adjustment for white matter hyperintensities and lacunes did not change these results. CBF in frontal, temporal and cerebellar regions was not associated with cognitive decline. Conclusions: Lower CBF, in particular in the parietal lobes, is associated with a steeper decline on the MMSE. These findings indicate that CBF as measured with ASL may have value as prognostic marker for cognitive decline in patients with AD.
U
Data are represented as b6SE. Linear mixed models were used to investigate associations between CBF and change in MMSE. A random intercept and random slope for time (in years) were assumed. The model includes terms for the CBF measure, time, the interaction between the CBF measure and time and covariates. The given b in each first column represents the difference in baseline MMSE. In each second column, the b represents the difference in annual MMSE change. Negative values indicate that a lower CBF is associated with a decline in MMSE. Model 1: adjusted for age, sex, education and NBV. Model 2: additional adjustment for WMH and lacunes. *p< 0.05; Up¼0.05; #p¼0.06; x CBF was inverted (i.e., higher is worse) and given per SD deviation increase (worsening).
CBF
Global
Memory
Attention
Language
Visuospatial functioning
Whole brain Parietal Frontal Temporal Occipital Cerebellum
.10 .05 .12 .15 -.00 .12
.19 .15 .29** .20 .03 .14
.06 .07 .01 .04 .08 -.02
.09 .08 .09 .10 .02 -.03
.20 .16 .21 .12 .12 .12
.06 .02 .04 .02 .01 .02
Executive functioning .13 .17* .11 .16* .14* -.00
Executive functioning
Alzheimer’s disease
CBF
Global
Memory
Attention
Language
Visuospatial functioning
Whole brain Parietal Frontal Temporal Occipital Cerebellum
.11 .13 .11 .14 .08 -.01
.06 .10 .07 .08 .06 .00
.07 .08 .02 .06 .09 -.03
.20* .17* .20* .23** .16* .12
.13 .16 .02 .10 .26** .10
Data are represented as standardized beta coefficient. The given beta represents the association between CBF and the different cognitive domains. Cognition is expressed as a (composite) z-score. CBF: cerebral blood flow. Adjusted for age. gender and education, white matter hypenntensities. presence of lacunes and normalized brain volume. *p<0.05, **p<0.001.
Poster Presentations: P4
Ab-Ptau-pos> Ptau-pos> Ab-pos> Ab-Ptau-neg. However, a significant interaction among time, Ab and PTau levels was reported only for RD (F(1,669)¼ 5.64, p¼ .02) and MD (F(1,669)¼ 7.01, p¼ .01). Ab-Ptau-pos showed higher increased in RD relative to aMCI without neurodegeneration (Ab-Ptau-neg and Ab-pos; Tukey’s test, p<.050) and higher MD increase compared to Ab-pos (Tukey’s test, p<.05). No significant FA and L1 alterations were observed. Conclusions: These preliminary data suggest that in aMCI patients i) amyloid pathology affects in white matter diffusion only when neurodegeneration coexists and ii) RD and MD seems more sensitive than FA and L1 to detect longitudinal diffusion changes. Longitudinal analysis is still ongoing. Pharmacog is funded by the EU-FP7 for the Innovative Medicine Initiative (grant 115009).
P4-088
LOWER CEREBRAL BLOOD FLOW IS ASSOCIATED WITH COGNITIVE DECLINE IN PATIENTS WITH ALZHEIMER’S DISEASE
Marije Benedictus, Annebet Leeuwis, Joost Kuijer, Philip Scheltens, Frederik Barkhof, M. Wiesje van der Flier, Niels Prins, VU University Medical Center, Amsterdam, Netherlands. Contact e-mail: m.benedictus@ vumc.nl Background: Cerebral blood flow (CBF) is lower in patient with Alzheimer’s disease (AD) compared to the general elderly population. We aimed to investigate whether lower CBF was associated with a more rapid cognitive decline in patients with AD. Methods: We included 88 AD patients from the Amsterdam dementia cohort, with an arterial spin labeling (ASL) scan at baseline and at least one year of clinical follow-up. 3T pseudocontinuous (PC-)ASL was used to determine whole brain and regional (parietal, frontal, occipital, temporal and cerebellar) CBF (ml/100gr/min). For statistical purposes, CBF was inverted
Table 1 Associations of CBF with baseline MMSE and annual change in MMSE Model 1 Cerebral blood flowx Whole brain Parietal Frontal Temporal Occipital Cerebellum
Estimated baseline MMSE -0.3260.39 -0.5060.41 -0.0260.43 -0.2060.39 -0.2960.38 0.2660.39
U
-0.50+0.25 -0.59+0.25* -0.1460.26 -0.4660.25 -0.47+0.25# -0.1860.26
Estimated baseline MMSE -0.2860.39 -0.45+0.41 0.1260.43 -0.17+0.39 -0.2360.39 0.3060.40
Estimated annual change in MMSE -0.49±10.25 -0.59±0.25* -0.1260.26 -0.4760.25 -0.47±0.25# -0.1760.26
P4-089
LOWER CEREBRAL BLOOD FLOW IS RELATED TO MORE SEVERE COGNITIVE IMPAIRMENT IN PATIENTS WITH DEMENTIA DUE TO ALZHEIMER’S DISEASE
Annebet Leeuwis1, Marije Benedictus1, Joost Kuijer1, Philip Scheltens1,2, Frederik Barkhof1,2, Niels Prins1, Wiesje M. van der Flier1,2, 1VU University Medical Center, Amsterdam, Netherlands; 2Neuroscience Campus Amsterdam, Amsterdam, Netherlands. Contact e-mail: [email protected] Table 1 Associations between CBF and cognitive domains in patients with mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) Mild cognitive impairment
Model 2
Estimated annual change in MMSE
(i.e., higher is worse) and standardized. Linear mixed models were used to determine associations between CBF and cognitive decline over time as measured with the MMSE. We adjusted for age, sex, education and normalized brain volume, and in a separate model additionally for white matter hyperintensities and lacunes. Results: Patients were 6567 years old, 44 (50%) were female and mean baseline MMSE was 2264. Mean follow-up of 2.160.8 years and patients declined with -2.263.0 MMSE points per year. Linear mixed models revealed no associations between whole brain or regional CBF with baseline MMSE (table 1). One standard deviation (SD) lower whole brain CBF was associated with a steeper decline of 0.5 MMSE points per year (Model 1: b[SE] -0.50[0.25], p¼0.05). In particular, lower parietal CBF was associated with steeper annual decline on the MMSE (Model 1: b[SE] -0.59[0.25], p<0.05). Lower occipital CBF tended to be associated with cognitive decline as well (Model 1: b[SE] - 0.47[0.25], p¼0.06). Additional adjustment for white matter hyperintensities and lacunes did not change these results. CBF in frontal, temporal and cerebellar regions was not associated with cognitive decline. Conclusions: Lower CBF, in particular in the parietal lobes, is associated with a steeper decline on the MMSE. These findings indicate that CBF as measured with ASL may have value as prognostic marker for cognitive decline in patients with AD.
U
Data are represented as b6SE. Linear mixed models were used to investigate associations between CBF and change in MMSE. A random intercept and random slope for time (in years) were assumed. The model includes terms for the CBF measure, time, the interaction between the CBF measure and time and covariates. The given b in each first column represents the difference in baseline MMSE. In each second column, the b represents the difference in annual MMSE change. Negative values indicate that a lower CBF is associated with a decline in MMSE. Model 1: adjusted for age, sex, education and NBV. Model 2: additional adjustment for WMH and lacunes. *p< 0.05; Up¼0.05; #p¼0.06; x CBF was inverted (i.e., higher is worse) and given per SD deviation increase (worsening).
CBF
Global
Memory
Attention
Language
Visuospatial functioning
Whole brain Parietal Frontal Temporal Occipital Cerebellum
.10 .05 .12 .15 -.00 .12
.19 .15 .29** .20 .03 .14
.06 .07 .01 .04 .08 -.02
.09 .08 .09 .10 .02 -.03
.20 .16 .21 .12 .12 .12
.06 .02 .04 .02 .01 .02
Executive functioning .13 .17* .11 .16* .14* -.00
Executive functioning
Alzheimer’s disease
CBF
Global
Memory
Attention
Language
Visuospatial functioning
Whole brain Parietal Frontal Temporal Occipital Cerebellum
.11 .13 .11 .14 .08 -.01
.06 .10 .07 .08 .06 .00
.07 .08 .02 .06 .09 -.03
.20* .17* .20* .23** .16* .12
.13 .16 .02 .10 .26** .10
Data are represented as standardized beta coefficient. The given beta represents the association between CBF and the different cognitive domains. Cognition is expressed as a (composite) z-score. CBF: cerebral blood flow. Adjusted for age. gender and education, white matter hypenntensities. presence of lacunes and normalized brain volume. *p<0.05, **p<0.001.