Cognitive impairment networks in Alzheimer's disease: Analysis of three double-blind randomized, placebo-controlled, clinical trials of donepezil

Rotstein, Anat; Levine, Stephen Z.; Samara, Myrto; Yoshida, Katsukuni; Goldberg, Yair; Cipriani, Andrea; Iwatsubo, Takeshi; Leucht, Stefan; Furukawa, Toshi A

doi:10.1016/j.euroneuro.2022.01.001

Cited by 2 publications

(6 citation statements)

References 31 publications

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“…Considering decomposition into occasion‐specific, trait, and accumulated effects, these items from the language and memory subdomains may capture AD‐related cognitive changes over time most effectively, as they were most highly influenced by accumulated effects (vs. occasion‐specific or trait effects). Previous psychometric network analysis showed that item 10 “comprehension of spoken language” appeared to be the most sensitive to psychopharmacological intervention, suggesting that it might be the most important to monitor among outcomes 27 . This item is a subjective observation made by the examiner, so high reliability might not have been anticipated.…”

Section: Discussionmentioning

confidence: 99%

“…Previous psychometric network analysis showed that item 10 “comprehension of spoken language” appeared to be the most sensitive to psychopharmacological intervention, suggesting that it might be the most important to monitor among outcomes. 27 This item is a subjective observation made by the examiner, so high reliability might not have been anticipated. Nonetheless, our results concur, and our approach provides two possible theoretical bases for that finding.…”

Section: Discussionmentioning

confidence: 99%

“…29 If language item scores are reliable and most heavily influenced by the progression of mild AD, the clinical trial data might be reassessed post hoc using language subdomain items, or specifically "comprehension of spoken language," as most items from the other subdomains were less reliable, and their reliable information was more heavily related to interindividual trait differences. This may have diluted the efficacy measurement, as suggested empirically in the context of trials by Rotstein et al 27 Memory scores, in particular the items "word recall" and "delayed word," were found also to be fairly reliable with similar contributions of accumulated effects to the reliable, consistent information that they yield. In contrast, studies of the cholinesterase inhibitors showed effects on the ADAS-Cog; however, treatment efficacy is known to wane over extended timelines such as those in this study, suggesting that those shorter term changes on the ADAS-Cog may not be relevant to longer term decline described here.…”

Section: F I G U R Ementioning

confidence: 93%

“…the most important to monitor among outcomes. 27 This item is a subjective observation made by the examiner, so high reliability might not have been anticipated. Nonetheless, our results concur, and our approach provides two possible theoretical bases for that finding.…”

Section: F I G U R Ementioning

confidence: 99%

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State, trait, and accumulated features of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog) in mild Alzheimer's disease

Cogo‐Moreira

Krance

et al. 2023

A&D Transl Res & Clin Interv

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Background The Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog) is used to assess decline in memory, language, and praxis in Alzheimer's disease (AD). Methods A latent state–trait model with autoregressive effects was used to determine how much of the ADAS‐Cog item measurement was reliable, and of that, how much of the information was occasion specific (state) versus consistent (trait or accumulated from one visit to the next). Results Participants with mild AD (n = 341) were assessed four times over 24 months. Praxis items were generally unreliable as were some memory items. Language items were generally the most reliable, and this increased over time. Only two ADAS‐Cog items showed reliability >0.70 at all four assessments, word recall (memory) and naming (language). Of the reliable information, language items exhibited greater consistency (63.4% to 88.2%) than occasion specificity, and of the consistent information, language items tended to reflect effects of AD progression that accumulated from one visit to the next (35.5% to 45.3%). In contrast, reliable information from praxis items tended to come from trait information. The reliable information in the memory items reflected more consistent than occasion‐specific information, but they varied between items in the relative amounts of trait versus accumulated effects. Conclusions Although the ADAS‐Cog was designed to track cognitive decline, most items were unreliable, and each item captured different amounts of information related to occasion‐specific, trait, and accumulated effects of AD over time. These latent properties complicate the interpretation of trends seen in ordinary statistical analyses of trials and other clinical studies with repeated ADAS‐Cog item measures. Highlights Studies have described unfavorable psychometric properties of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog), bringing into question its ability to track changes in cognition uniformly over time. There remains a need to estimate how much of the ADAS‐Cog measurement is reliable, of that how much is occasion specific versus consistent, and of the consistent information, how much represents enduring traits versus autoregressive effects (i.e., effects of Alzheimer's disease [AD] progression carried over from one assessment to the next). A latent state–trait model with autoregressive effects in mild AD found most items to be unreliable, and each item to capture different amounts of occasion‐specific, trait, and autoregressive information. Language items, specifically, naming and the memory item word recall, were the most reliable. Psychometric idiosyncrasies of individual items complicate the interpretation of their summed score, biasing ordinary statistical analyses of repeated measures in mild AD. Future studies should consider item trajectories individually.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: F I G U R Ementioning

confidence: 93%

Section: F I G U R Ementioning

confidence: 99%

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State, trait, and accumulated features of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog) in mild Alzheimer's disease

Cogo‐Moreira

Krance

et al. 2023

A&D Transl Res & Clin Interv

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“…The most recent study by Rotstein et al [75] evaluated psychometric networks of cognitive impairment in more than 1000 American patients with Alzheimer's disease assessed by the cognitive subscale of the Alzheimer's Disease Assessment Scale composed of seven domains: temporal and spatial orientation, attention, learning, memory, abstract thinking, verbal fluency, and naming. Several network systems were represented between two groups that received treatment with donepezil and placebo at 24 weeks of follow-up, the results showed a statistically significant difference in the global strength of the network integrated by the patients who received medication, evidencing a lower cognitive deterioration in this group.…”

Section: The Use Of Psychological Network Models In the Context Of Ne...mentioning

confidence: 99%

Psychometric Networks and Their Implications for the Treatment and Diagnosis of Psychopathologies

Ramos-Vera¹,

Franco²,

Saldarriaga³

et al. 2023

Psychometrics - New Insights in the Diagnosis of Mental Disorders

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In this chapter, we present the main methodological principles of psychological networks as a way of conceptualizing mental disorders. In the network approach, mental disorders are conceptualized as the consequence of direct interactions between symptoms, which may involve biological, psychological, and social mechanisms. If these cause-and-effect relationships are strong enough, symptoms can generate a degree of feedback to sustain them. It is discussed how such an approach contrasts with the traditional psychometric approach, known as the Latent Variable Theory, which assumes that disorders are constructs that exist but are not directly observable. Furthermore, it is also discussed how new neuropsychological hypotheses have been derived in the network approach and how such hypotheses generate direct implications for the understanding of diagnosis and treatment of psychological disorders. Finally, the recentness of the network approach in psychology and how future studies can establish its robustness are discussed.

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Cognitive impairment networks in Alzheimer's disease: Analysis of three double-blind randomized, placebo-controlled, clinical trials of donepezil

Cited by 2 publications

References 31 publications

State, trait, and accumulated features of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog) in mild Alzheimer's disease

State, trait, and accumulated features of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS‐Cog) in mild Alzheimer's disease

Psychometric Networks and Their Implications for the Treatment and Diagnosis of Psychopathologies

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