Dataset Information

Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

ABSTRACT:

Background

We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD).

Methods

Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, and education were explored using interaction terms and subgroup analyses.

Results

APOE ε4 was inversely associated with most cognitive measures (p < 0.05). This association was stronger with advancing age for the Hindi Mental State Examination (HMSE) score (β_ε4×age= -0.44, p = 0.03), orientation (β_ε4×age= -0.07, p = 0.01), and language/fluency (β_ε4×age= -0.07, p = 0.01), as well as in females for memory (β_ε4×male= 0.17, p = 0.02) and language/fluency (β_ε4×male= 0.12, p = 0.03).

Discussion

APOE ε4 is associated with lower cognitive function in South Asians from India, with a more pronounced impact observed in females and older individuals.

Highlights

APOE ε4 carriers had lower global and domain-specific cognitive performance. Females and older individuals may be more susceptible to ε4 effects. For most cognitive measures, there was no interaction between ε4 and education.

SUBMITTER: Wang YZ

PROVIDER: S-EPMC11247697 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

Wang Yi Zhe YZ Zhao Wei W Moorjani Priya P Gross Alden L AL Zhou Xiang X Dey Aparajit B AB Lee Jinkook J Smith Jennifer A JA Kardia Sharon L R SLR

Alzheimer's & dementia : the journal of the Alzheimer's Association 20240618 7

<h4>Background</h4>We investigated the effects of apolipoprotein E (APOE) ε4 and its interactions with sociodemographic characteristics on cognitive measures in South Asians from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD).<h4>Methods</h4>Linear regression was used to assess the association between APOE ε4 and global- and domain-specific cognitive function in 2563 participants (mean age 69.6 ± 7.3 years; 53% female). Effect modification by age, sex, ...[more]

PMID: 38889280

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Project description:ImportanceThe apolipoprotein E (APOE [GenBank, 348; OMIM, 107741]) ε4 allele is a common and well-established genetic risk factor for Alzheimer disease (AD). Sleep consolidation is also associated with AD risk, and previous work suggests that APOE genotype and sleep may interact to influence cognitive function.ObjectiveTo determine whether better sleep consolidation attenuates the relationship of the APOE genotype to the risk of incident AD and the burden of AD pathology.Design, setting, and participantsA prospective longitudinal cohort study with up to 6 years of follow-up was conducted. Participants included 698 community-dwelling older adults without dementia (mean age, 81.7 years; 77% women) in the Rush Memory and Aging Project.ExposuresWe used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation and ascertained APOE genotype.Main outcomes and measuresParticipants underwent annual evaluation for AD during a follow-up period of up to 6 years. Autopsies were performed on 201 participants who died, and β-amyloid (Aβ) and neurofibrillary tangles were identified by immunohistochemistry and quantified.ResultsDuring the follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards regression models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (hazard ratio, 0.67; 95% CI, 0.46-0.97; P = .04 per allele per 1-SD increase in sleep consolidation). In a series of linear mixed-effect models, better sleep consolidation also attenuated the effect of the ε4 allele on the annual rate of cognitive decline. In individuals who died, better sleep consolidation attenuated the effect of the ε4 allele on neurofibrillary tangle density (interaction estimate, -0.42; SE = 0.17; P = .02), which accounted for the effect of sleep consolidation on the association between APOE genotype and cognition proximate to death.Conclusions and relevanceBetter sleep consolidation attenuates the effect of APOE genotype on incident AD and development of neurofibrillary tangle pathology. Assessment of sleep consolidation may identify APOE+ individuals at high risk for incident AD, and interventions to enhance sleep consolidation should be studied as potentially useful means to reduce the risk of AD and development of neurofibrillary tangles in APOE ε4+ individuals.

Project description:Background and objectivesPrior investigations have not considered whether poor vision biases cognitive testing. However, such research is vital given increasing evidence that vision impairment (VI) may be an important modifiable risk factor for dementia, particularly in low- and middle-income settings where the prevalence of VI is high.Research design and methodsThis study employed data from 3 784 participants in Wave 1 of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) who underwent both visual acuity and cognitive function testing. We used multiple indicators and multiple causes models to assess differential item functioning (DIF; eg, bias) in cognitive testing by objectively measured distance and near VI. Multivariable linear regression was used to model the association between VI and cognitive factor scores before and after DIF adjustment. Analyses were performed for general cognition and separate cognitive domains, corresponding to memory, language/fluency, executive functioning, and visuospatial performance. Models were adjusted for demographic, health, and socioeconomic covariates.ResultsParticipants in our sample were 60 and older. Most participants with VI were 60-69 years old (59.6%) and 50.8% were female. Individuals experiencing both distance and near VI tended to be older, have lower educational attainment, be married, reside in rural settings, and belong to lower consumption and BMI categories. Both distance and near VI were associated with poorer cognition before and after DIF-adjustment. Differences between DIF-unadjusted and -adjusted scores were small compared to the standard error of measurement, indicating no evidence of meaningful measurement differences by VI.Discussion and implicationsIn well-conducted large-scale surveys, bias in cognitive testing due to VI is likely minimal. Findings strengthen previous evidence on the association between VI and dementia by showing that such associations are unlikely to be attributable to vision-related measurement error in the assessment of cognitive functioning.

Dataset Information

Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

Background

Methods

Results

Discussion

Highlights

Publications

Effect of apolipoprotein E ε4 and its modification by sociodemographic characteristics on cognitive measures in South Asians from LASI-DAD.

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