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Relationships of change in Clinical Dementia Rating (CDR) on patient outcomes and probability of progression : observational analysis

Tariot, Pierre N. ; Boada, Mercè ; Lanctôt, Krista L. ; Hahn-Pedersen, Julie ; Dabbous, Firas ; Udayachalerm, Sariya ; Raket, Lars Lau LU orcid ; Halchenko, Yuliya ; Michalak, Wojciech and Weidner, Wendy , et al. (2024) In Alzheimer's Research and Therapy 16(1).
Abstract

Background: Understanding the relationship among changes in Clinical Dementia Rating (CDR), patient outcomes, and probability of progression is crucial for evaluating the long-term benefits of disease-modifying treatments. We examined associations among changes in Alzheimer’s disease (AD) stages and outcomes that are important to patients and their care partners including activities of daily living (ADLs), geriatric depression, neuropsychiatric features, cognitive impairment, and the probabilities of being transitioned to a long-term care facility (i.e., institutionalization). We also estimated the total time spent at each stage and annual transition probabilities in AD. Methods: The study included participants with unimpaired... (More)

Background: Understanding the relationship among changes in Clinical Dementia Rating (CDR), patient outcomes, and probability of progression is crucial for evaluating the long-term benefits of disease-modifying treatments. We examined associations among changes in Alzheimer’s disease (AD) stages and outcomes that are important to patients and their care partners including activities of daily living (ADLs), geriatric depression, neuropsychiatric features, cognitive impairment, and the probabilities of being transitioned to a long-term care facility (i.e., institutionalization). We also estimated the total time spent at each stage and annual transition probabilities in AD. Methods: The study included participants with unimpaired cognition, mild cognitive impairment (MCI) due to AD, and mild, moderate, and severe AD dementia in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) database. The associations among change in AD stages and change in relevant outcomes were estimated using linear mixed models with random intercepts. The probability of transitioning to long-term care facilities was modeled using generalized estimating equations. The total length of time spent at AD stages and annual transition probabilities were estimated with multistate Markov models. Results: The estimated average time spent in each stage was 3.2 years in MCI due to AD and 2.2, 2.0, and 2.8 years for mild, moderate, and severe AD dementia, respectively. The annual probabilities of progressing from MCI to mild, moderate, and severe AD dementia were 20, 4, and 0.7%, respectively. The incremental change to the next stage of participants with unimpaired cognition, MCI, and mild, moderate, and severe AD dementia (to death) was 3.2, 20, 26.6, 31, and 25.3%, respectively. Changes in ADLs, neuropsychiatric features, and cognitive measures were greatest among participants who transitioned from MCI and mild AD dementia to more advanced stages. Participants with MCI and mild and moderate AD dementia had increasing odds of being transitioned to long-term care facilities over time during the follow-up period. Conclusions: The findings demonstrated that participants with early stages AD (MCI or mild dementia) were associated with the largest changes in clinical scale scores. Early detection, diagnosis, and intervention by disease-modifying therapies are required for delaying AD progression. Additionally, estimates of transition probabilities can inform future studies and health economic modeling.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Activities of daily living, Alzheimer’s disease, Burden, Clinical Dementia Rating, Cognitive impairment, Institutionalization, Long-term care facility, Neuropsychiatric features, Progression, Transition probabilities
in
Alzheimer's Research and Therapy
volume
16
issue
1
article number
36
publisher
BioMed Central (BMC)
external identifiers
  • pmid:38355706
  • scopus:85185314991
ISSN
1758-9193
DOI
10.1186/s13195-024-01399-7
language
English
LU publication?
yes
id
ea807b4a-fa65-4102-9500-bf73dbb3f911
date added to LUP
2024-03-14 12:00:32
date last changed
2024-04-25 08:39:16
@article{ea807b4a-fa65-4102-9500-bf73dbb3f911,
  abstract     = {{<p>Background: Understanding the relationship among changes in Clinical Dementia Rating (CDR), patient outcomes, and probability of progression is crucial for evaluating the long-term benefits of disease-modifying treatments. We examined associations among changes in Alzheimer’s disease (AD) stages and outcomes that are important to patients and their care partners including activities of daily living (ADLs), geriatric depression, neuropsychiatric features, cognitive impairment, and the probabilities of being transitioned to a long-term care facility (i.e., institutionalization). We also estimated the total time spent at each stage and annual transition probabilities in AD. Methods: The study included participants with unimpaired cognition, mild cognitive impairment (MCI) due to AD, and mild, moderate, and severe AD dementia in the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS) database. The associations among change in AD stages and change in relevant outcomes were estimated using linear mixed models with random intercepts. The probability of transitioning to long-term care facilities was modeled using generalized estimating equations. The total length of time spent at AD stages and annual transition probabilities were estimated with multistate Markov models. Results: The estimated average time spent in each stage was 3.2 years in MCI due to AD and 2.2, 2.0, and 2.8 years for mild, moderate, and severe AD dementia, respectively. The annual probabilities of progressing from MCI to mild, moderate, and severe AD dementia were 20, 4, and 0.7%, respectively. The incremental change to the next stage of participants with unimpaired cognition, MCI, and mild, moderate, and severe AD dementia (to death) was 3.2, 20, 26.6, 31, and 25.3%, respectively. Changes in ADLs, neuropsychiatric features, and cognitive measures were greatest among participants who transitioned from MCI and mild AD dementia to more advanced stages. Participants with MCI and mild and moderate AD dementia had increasing odds of being transitioned to long-term care facilities over time during the follow-up period. Conclusions: The findings demonstrated that participants with early stages AD (MCI or mild dementia) were associated with the largest changes in clinical scale scores. Early detection, diagnosis, and intervention by disease-modifying therapies are required for delaying AD progression. Additionally, estimates of transition probabilities can inform future studies and health economic modeling.</p>}},
  author       = {{Tariot, Pierre N. and Boada, Mercè and Lanctôt, Krista L. and Hahn-Pedersen, Julie and Dabbous, Firas and Udayachalerm, Sariya and Raket, Lars Lau and Halchenko, Yuliya and Michalak, Wojciech and Weidner, Wendy and Cummings, Jeffrey}},
  issn         = {{1758-9193}},
  keywords     = {{Activities of daily living; Alzheimer’s disease; Burden; Clinical Dementia Rating; Cognitive impairment; Institutionalization; Long-term care facility; Neuropsychiatric features; Progression; Transition probabilities}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research and Therapy}},
  title        = {{Relationships of change in Clinical Dementia Rating (CDR) on patient outcomes and probability of progression : observational analysis}},
  url          = {{http://dx.doi.org/10.1186/s13195-024-01399-7}},
  doi          = {{10.1186/s13195-024-01399-7}},
  volume       = {{16}},
  year         = {{2024}},
}