TY - JOUR
T1 - Cognitive impairment networks in Alzheimer's disease
T2 - Analysis of three double-blind randomized, placebo-controlled, clinical trials of donepezil
AU - Rotstein, Anat
AU - Levine, Stephen Z.
AU - Samara, Myrto
AU - Yoshida, Kazufumi
AU - Goldberg, Yair
AU - Cipriani, Andrea
AU - Iwatsubo, Takeshi
AU - Leucht, Stefan
AU - Furukawa, Toshiaki A.
N1 - Publisher Copyright:
© 2022 Elsevier B.V. and ECNP
PY - 2022/4
Y1 - 2022/4
N2 - Psychometric network analysis is an alternative theoretically-driven analytic approach that has the potential to conceptualize cognitive impairment in Alzheimer's disease differently than was previously assumed and consequently detect unknown treatment effects. Based on individual participant data, extracted from three double-blind, randomized placebo-controlled clinical trials, psychometric networks were computed on observed Alzheimer's Disease Assessment Scale Cognitive Subscale scores at baseline (N=1,554) and on predicted change scores at 24 weeks of follow-up for participants who received donepezil (N=797) or placebo (N=484). A novel conceptualization of cognitive impairment in Alzheimer's disease was displayed through the baseline network, that had 90% (n=27) positive statistically significant (p<0.05) associations, and a most central aspect of ideational praxis. Following 24 weeks, treatment effects emerged via the differences between the change score networks. The donepezil network had more statistically significant (p<0.05) positive associations and a higher global strength (n=15; S=1.22; p=0.03), than the placebo network (n=8; S=0.57). This suggests that for those who were treated with donepezil compared with placebo, cognition is a more unified construct. The main aspects of change in cognitive impairment were comprehension of spoken language for the donepezil network and spoken language ability for the placebo network. Comprehension of spoken language apears to be most sensitive to psychopharmaceutical interventions and should therefore be closely monitored. Overall, our psychometric network analysis presents a new conceptualization of cognitive impairment in Alzheimer's disease, points to previously unknown treatment effects and highlights well-defined aspects of cognitive impairment that may translate into future treatment targets.
AB - Psychometric network analysis is an alternative theoretically-driven analytic approach that has the potential to conceptualize cognitive impairment in Alzheimer's disease differently than was previously assumed and consequently detect unknown treatment effects. Based on individual participant data, extracted from three double-blind, randomized placebo-controlled clinical trials, psychometric networks were computed on observed Alzheimer's Disease Assessment Scale Cognitive Subscale scores at baseline (N=1,554) and on predicted change scores at 24 weeks of follow-up for participants who received donepezil (N=797) or placebo (N=484). A novel conceptualization of cognitive impairment in Alzheimer's disease was displayed through the baseline network, that had 90% (n=27) positive statistically significant (p<0.05) associations, and a most central aspect of ideational praxis. Following 24 weeks, treatment effects emerged via the differences between the change score networks. The donepezil network had more statistically significant (p<0.05) positive associations and a higher global strength (n=15; S=1.22; p=0.03), than the placebo network (n=8; S=0.57). This suggests that for those who were treated with donepezil compared with placebo, cognition is a more unified construct. The main aspects of change in cognitive impairment were comprehension of spoken language for the donepezil network and spoken language ability for the placebo network. Comprehension of spoken language apears to be most sensitive to psychopharmaceutical interventions and should therefore be closely monitored. Overall, our psychometric network analysis presents a new conceptualization of cognitive impairment in Alzheimer's disease, points to previously unknown treatment effects and highlights well-defined aspects of cognitive impairment that may translate into future treatment targets.
KW - ADAS-cog
KW - Cognitive functioning
KW - Network-analysis
KW - Predicted change scores
KW - The Alzheimer's disease assessment scale cognitive subscale
UR - http://www.scopus.com/inward/record.url?scp=85123615699&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2022.01.001
DO - 10.1016/j.euroneuro.2022.01.001
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 35093678
AN - SCOPUS:85123615699
SN - 0924-977X
VL - 57
SP - 50
EP - 58
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -