Rates of Progression in Patients with Alzheimer’s Disease Depending on Apolipoprotein E Genotype and Concomitant Medications.
(2023) 16th Clinical Trials on Alzheimer's Disease Conference- Abstract
- Background: The apolipoprotein E (APOE) ε4 allele is associated with higher cholesterol levels, and an increased risk of developing Alzheimer’s disease (AD) and amyloid-related imaging abnormalities after initiation of amyloid-modifying therapies. A worse cognitive response to cholinesterase inhibitor (ChEI) treatment and longitudinal outcome in APOE ε4-carriers has been observed. Based on these clinical findings, cholesterol and the APOE ε4 allele may affect beta-amyloid burden, metabolism, and inflammation in the brain. Younger age at onset and at diagnosis of AD have also been reported in APOE ε4-carriers. Younger persons usually have less comorbidity and fewer concomitant medications that may affect the outcome of AD. Objectives: This... (More)
- Background: The apolipoprotein E (APOE) ε4 allele is associated with higher cholesterol levels, and an increased risk of developing Alzheimer’s disease (AD) and amyloid-related imaging abnormalities after initiation of amyloid-modifying therapies. A worse cognitive response to cholinesterase inhibitor (ChEI) treatment and longitudinal outcome in APOE ε4-carriers has been observed. Based on these clinical findings, cholesterol and the APOE ε4 allele may affect beta-amyloid burden, metabolism, and inflammation in the brain. Younger age at onset and at diagnosis of AD have also been reported in APOE ε4-carriers. Younger persons usually have less comorbidity and fewer concomitant medications that may affect the outcome of AD. Objectives: This longitudinal study examined potential differences in cognitive and functional progression rates in AD between patients with different APOE genotypes and concomitant medications. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective observational clinical practice-based multicenter study for evaluation of long-term effectiveness of ChEI therapy. Here, 999 outpatients (320 APOE non-ε4-carriers and 679 ε4-carriers) clinically diagnosed with mild-to-moderate AD (Mini-Mental State Examination [MMSE] score, 10–26) at the start of ChEI treatment (baseline) were enrolled. Participants were assessed for cognitive (MMSE) and functional performance (Instrumental Activities of Daily Living scale [IADL] and Physical Self-Maintenance Scale [PSMS]) at baseline and every 6 months for 3 years. Univariate general linear models were used to investigate whether usage of specific concomitant medications (antihypertensive/cardiac therapy, antidiabetic drugs, asthma medication, thyroid therapy, lipid-lowering agents, estrogens, nonsteroidal anti-inflammatory drugs/acetylsalicylic acid, antidepressants, antipsychotics, and anxiolytics/sedatives/hypnotics) affected the rates of disease progression in patients with or without the APOE ε4 allele. The outcomes were adjusted for sex, age at baseline, years of education, and cognitive and functional abilities at baseline. Results: Annual cognitive decline was faster in APOE non-ε4-carriers receiving lipid-lowering agents vs. nonusers (p=0.036). In contrast, cognitive progression rate was slower in ε4-carriers receiving lipid-lowering agents vs. nonusers (p=0.006). Cognitive decline was faster in APOE ε4-carriers receiving anxiolytics/sedatives/hypnotics vs. nonusers (p=0.034); this difference was not found in non-ε4-carriers. A faster annual progression rate in both IADL and basic ADL was demonstrated in APOE non-ε4-carriers receiving antidepressants vs. nonusers (p≤0.012); these differences were not observed in ε4-carriers. Moreover, APOE non-ε4-carriers receiving antipsychotics had faster IADL deterioration vs. nonusers (p=0.003); this difference was not detected in ε4-carriers. Conclusion: Various concomitant medications and comorbidities might affect the cognitive and functional outcomes of AD differently depending on APOE genotype. APOE ε4-carriers, but not non-ε4-carriers, who received lipid-lowering agents showed a slower cognitive decline than nonusers. Because the APOE ε4 allele is known to be associated with higher cholesterol levels and has been implicated in AD-related processes, such as beta-amyloid burden and inflammation, ε4-carriers may benefit more from use of statins. A risk factor for faster cognitive decline among APOE ε4-carriers only was treatment with anxiolytics/sedatives/hypnotics, suggesting that these individuals might be more prone to the related adverse effects. In non-ε4-carriers, neuropsychiatric symptoms were risk factors for faster functional deterioration, particularly in IADL, which is an important measure of independent living. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/c44c10d6-35e7-44fd-92ca-fc24a01275db
- author
- Wattmo, Carina LU
- organization
- publishing date
- 2023
- type
- Contribution to conference
- publication status
- published
- subject
- conference name
- 16th Clinical Trials on Alzheimer's Disease Conference
- conference location
- Boston, United States
- conference dates
- 2023-10-24 - 2023-10-27
- DOI
- 10.13140/RG.2.2.10722.91842
- language
- English
- LU publication?
- yes
- id
- c44c10d6-35e7-44fd-92ca-fc24a01275db
- date added to LUP
- 2023-11-08 17:15:46
- date last changed
- 2023-11-09 11:33:25
@misc{c44c10d6-35e7-44fd-92ca-fc24a01275db,
abstract = {{Background: The apolipoprotein E (APOE) ε4 allele is associated with higher cholesterol levels, and an increased risk of developing Alzheimer’s disease (AD) and amyloid-related imaging abnormalities after initiation of amyloid-modifying therapies. A worse cognitive response to cholinesterase inhibitor (ChEI) treatment and longitudinal outcome in APOE ε4-carriers has been observed. Based on these clinical findings, cholesterol and the APOE ε4 allele may affect beta-amyloid burden, metabolism, and inflammation in the brain. Younger age at onset and at diagnosis of AD have also been reported in APOE ε4-carriers. Younger persons usually have less comorbidity and fewer concomitant medications that may affect the outcome of AD. Objectives: This longitudinal study examined potential differences in cognitive and functional progression rates in AD between patients with different APOE genotypes and concomitant medications. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective observational clinical practice-based multicenter study for evaluation of long-term effectiveness of ChEI therapy. Here, 999 outpatients (320 APOE non-ε4-carriers and 679 ε4-carriers) clinically diagnosed with mild-to-moderate AD (Mini-Mental State Examination [MMSE] score, 10–26) at the start of ChEI treatment (baseline) were enrolled. Participants were assessed for cognitive (MMSE) and functional performance (Instrumental Activities of Daily Living scale [IADL] and Physical Self-Maintenance Scale [PSMS]) at baseline and every 6 months for 3 years. Univariate general linear models were used to investigate whether usage of specific concomitant medications (antihypertensive/cardiac therapy, antidiabetic drugs, asthma medication, thyroid therapy, lipid-lowering agents, estrogens, nonsteroidal anti-inflammatory drugs/acetylsalicylic acid, antidepressants, antipsychotics, and anxiolytics/sedatives/hypnotics) affected the rates of disease progression in patients with or without the APOE ε4 allele. The outcomes were adjusted for sex, age at baseline, years of education, and cognitive and functional abilities at baseline. Results: Annual cognitive decline was faster in APOE non-ε4-carriers receiving lipid-lowering agents vs. nonusers (p=0.036). In contrast, cognitive progression rate was slower in ε4-carriers receiving lipid-lowering agents vs. nonusers (p=0.006). Cognitive decline was faster in APOE ε4-carriers receiving anxiolytics/sedatives/hypnotics vs. nonusers (p=0.034); this difference was not found in non-ε4-carriers. A faster annual progression rate in both IADL and basic ADL was demonstrated in APOE non-ε4-carriers receiving antidepressants vs. nonusers (p≤0.012); these differences were not observed in ε4-carriers. Moreover, APOE non-ε4-carriers receiving antipsychotics had faster IADL deterioration vs. nonusers (p=0.003); this difference was not detected in ε4-carriers. Conclusion: Various concomitant medications and comorbidities might affect the cognitive and functional outcomes of AD differently depending on APOE genotype. APOE ε4-carriers, but not non-ε4-carriers, who received lipid-lowering agents showed a slower cognitive decline than nonusers. Because the APOE ε4 allele is known to be associated with higher cholesterol levels and has been implicated in AD-related processes, such as beta-amyloid burden and inflammation, ε4-carriers may benefit more from use of statins. A risk factor for faster cognitive decline among APOE ε4-carriers only was treatment with anxiolytics/sedatives/hypnotics, suggesting that these individuals might be more prone to the related adverse effects. In non-ε4-carriers, neuropsychiatric symptoms were risk factors for faster functional deterioration, particularly in IADL, which is an important measure of independent living.}},
author = {{Wattmo, Carina}},
language = {{eng}},
title = {{Rates of Progression in Patients with Alzheimer’s Disease Depending on Apolipoprotein E Genotype and Concomitant Medications.}},
url = {{https://lup.lub.lu.se/search/files/164608645/Poster_Wattmo_CTAD_Boston_2023_-_Poster_40x46_in_-_Tryckfil.pdf}},
doi = {{10.13140/RG.2.2.10722.91842}},
year = {{2023}},
}