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Gustavson, D. E., Bell, T. R., Buchholz, E. J., Zellers, S., Luczak, S. E., Reynolds, C. A., . . . Consortium, I. G. (2025). Genetic and Environmental Influences on Alcohol Consumption in Middle to Late Life. Psychology of Addictive Behaviors
Open this publication in new window or tab >>Genetic and Environmental Influences on Alcohol Consumption in Middle to Late Life
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2025 (English)In: Psychology of Addictive Behaviors, ISSN 0893-164X, E-ISSN 1939-1501Article in journal (Refereed) Epub ahead of print
Abstract [en]

Objective: Alcohol use is common in older adults and linked to poor health and aging outcomes. Studies have demonstrated genetic and environmental contributions to the quantity of alcohol consumption in mid-to-late life, but less is known about whether these influences are moderated by sociodemographic factors such as age, sex, and educational attainment. This study sought to better understand sociodemographic trends in alcohol consumption across the second half of the life course and their underlying genetic and environmental influences. Method: Primary analyses were based on 64,140 middle-aged or older adult twins (40-102 years) from 14 studies in the Interplay of Genes and Environment Across Multiple Studies consortium. We harmonized a measure of weekly alcohol consumption (in grams of ethanol per week) across all studies. Results: Older age was associated with lower alcohol consumption, primarily for adults over age 75, for individuals with higher education, and for males. Trends were similar across birth cohorts and after excluding current abstainers. At mean age 56, alcohol use was moderately heritable in females (.34, 95% CI [.26, .41]) and more heritable in males (.42, 95% CI [.38, .45]). Heritability was lower in older aged adults and in females with higher education. Conclusions: This study represents the largest twin study of alcohol consumption in middle-aged and older adults. Results highlight that genetic and environmental factors influence alcohol consumption differently across age, sex, and educational attainment and that intervention efforts may need to be tailored based on individuals' backgrounds. Public Health Significance Statement Prior genetic studies of alcohol use have focused on adolescent and adult samples, despite the fact that it is common in older adults and linked to poor health and aging outcomes. This study demonstrates that genetic and environmental influences on alcohol consumption in middle-aged and older adults vary based on age, sex, and educational attainment.

Place, publisher, year, edition, pages
American Psychological Association (APA), 2025
Keywords
heritability, twin study, alcohol, Gene x Environment interaction, aging
National Category
Substance Abuse
Identifiers
urn:nbn:se:hj:diva-67061 (URN)10.1037/adb0001052 (DOI)001392733600001 ()39786837 (PubMedID)2-s2.0-85215866755 (Scopus ID);intsam;993809 (Local ID);intsam;993809 (Archive number);intsam;993809 (OAI)
Funder
NIH (National Institutes of Health)Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council
Available from: 2025-01-16 Created: 2025-01-16 Last updated: 2025-02-03
Finkel, D., Gatz, M., Franz, C. E., Catts, V. S., Christensen, K., Kremen, W., . . . Pedersen, N. L. (2024). Age and sex differences in the genetic architecture of measures of subjective health: Relationships with physical health, depressive symptoms, and episodic memory. The journals of gerontology. Series B, Psychological sciences and social sciences, 79(6), Article ID gbae062.
Open this publication in new window or tab >>Age and sex differences in the genetic architecture of measures of subjective health: Relationships with physical health, depressive symptoms, and episodic memory
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2024 (English)In: The journals of gerontology. Series B, Psychological sciences and social sciences, ISSN 1079-5014, E-ISSN 1758-5368, Vol. 79, no 6, article id gbae062Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Subjective health (SH) is not just an indicator of physical health, but also reflects active cognitive processing of information about one's own health and has been associated with emotional health measures, such as neuroticism and depression. Behavior genetic approaches investigate the genetic architecture of SH, i.e., genetic and environmental influences on individual differences in SH and associations with potential components such as physical, cognitive, and emotional health. Previous twin analyses have been limited by sex, sample size, age range, and focus on single covariates.

METHODS: The current analysis used data from 24,173 adults ranging in age from 40-90 years from the international Interplay of Genes and Environment Across Multiple Studies (IGEMS) consortium to investigate the genetic architecture of three measures of SH: self-rated health, health compared to others, and impact of health on activities. Independent pathways model of SH included physical health, depressive symptoms, and episodic memory, with age, sex, and country included as covariates.

RESULTS: Most or all of the genetic variance for SH measures was shared with physical health, depressive symptoms, and episodic memory. Genetic architecture of SH differed across measures, age groups (40-65, 66-90), and sexes. Age comparisons indicated stronger correlations with all 3 covariates in older adults, often resulting from greater shared genetic variance.

DISCUSSION: The predictive value of SH has been amply demonstrated. The higher genetic contributions to associations between SH and its components in older adults support the increasing conceptualization with age of SH as an intuitive summation of one's vital reserve.

Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
CIRS, SRH, Twins, Word recall
National Category
Gerontology, specialising in Medical and Health Sciences Medical Genetics Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:hj:diva-64156 (URN)10.1093/geronb/gbae062 (DOI)001230684300002 ()38632885 (PubMedID)2-s2.0-85194349303 (Scopus ID);intsam;1856793 (Local ID);intsam;1856793 (Archive number);intsam;1856793 (OAI)
Available from: 2024-05-08 Created: 2024-05-08 Last updated: 2024-10-10Bibliographically approved
Bell, S. A., Beam, C. R., Finkel, D., Barna, A. C., King, A., Sikes, K., . . . Turkheimer, E. (2024). Basic Science and Pathogenesis. Alzheimer's & Dementia: Journal of the Alzheimer's Association, 20, Article ID e093357.
Open this publication in new window or tab >>Basic Science and Pathogenesis
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2024 (English)In: Alzheimer's & Dementia: Journal of the Alzheimer's Association, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 20, article id e093357Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: DNA methylation (DNAm) age measures, or 'epigenetic clocks', surpass chronological age in their ability to predict age-related morbidities and mortality. The Louisville Twin Study (LTS) presents an opportunity to clarify the role of early life environmental exposures and development in biological and cognitive aging in midlife. We expect that second-generation DNAm age measures trained to predict age related outcomes and death, independent of chronological age, will be sensitive to cognitive ability in midlife. METHOD: Data collection of the midlife phase of the LTS is ongoing. This study utilizes data from 281 middle-aged twins, including 56 monozygotic and 41 dizygotic complete twin pairs (mean age 51.9 years ± 7.03). Midlife cognitive ability (IQ) was measured using the Wechsler Adult Intelligence Scale Fourth Edition. DNAm age acceleration was calculated using five clock algorithms: Horvath 1, Horvath 2, Hannum, GrimAge, and PhenoAge. We conducted an exploratory factor analysis to identify common factors as latent variables among the five clocks. Composite scores for factors were calculated, and genetically informed, quasi-causal regression models were fitted in which adult IQ was predicted from childhood socioeconomic status (SES), DNAm factor composite score, and the interaction between DNAm age and SES. RESULT: Factor analysis produced a two-factor structure: first-generation clocks (Horvath 1, Horvath 2, and Hannum) and second-generation clocks (PhenoAge and GrimAge). As predicted, childhood IQ and childhood SES predict adult IQ. Acceleration in the second-generation factor predicts lower midlife cognitive ability (b = -0.15, SE = 0.068, p <.05). Additionally, there is an interaction in the second-generation model such that people raised in higher SES families show a less negative relationship between DNAm age acceleration and adult IQ (b = 0.092, SE = 0.036, p <.05). However, there is no significant effect of the first-generation factor on adult IQ, and no SES interaction effect. CONCLUSION: Second-generation DNAm age measures show promise in their predictive value for cognitive aging processes. Moreover, the longitudinal twin design of the LTS serves as a quasi-experimental framework to investigate hypothesized causal effects of DNAm on cognitive aging. Finally, our findings related to childhood SES suggest that the epigenome is malleable and responsive to early-life stressors.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
Adult, Aging, Cognition, DNA Methylation, Epigenesis, Genetic, Female, Humans, Intelligence, Male, Middle Aged, Twins, Dizygotic, Twins, Monozygotic, dizygotic twinning, genetic epigenesis, genetics, human, monozygotic twinning, physiology, twin study
National Category
Neurosciences
Identifiers
urn:nbn:se:hj:diva-67085 (URN)10.1002/alz.093357 (DOI)2-s2.0-85214523016 (Scopus ID)GOA;;995168 (Local ID)GOA;;995168 (Archive number)GOA;;995168 (OAI)
Available from: 2025-01-21 Created: 2025-01-21 Last updated: 2025-01-21Bibliographically approved
Ler, P., Ojalehto, E., Zhan, Y., Finkel, D., Dahl Aslan, A. K. & Karlsson, I. K. (2024). Conversions between metabolically unhealthy and healthy obesity from midlife to late-life. International Journal of Obesity, 48, 433-436
Open this publication in new window or tab >>Conversions between metabolically unhealthy and healthy obesity from midlife to late-life
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2024 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 48, p. 433-436Article in journal (Refereed) Published
Abstract [en]

Introduction: Metabolically healthy obesity may be a transient phenotype, but studies with long follow-up, especially covering late-life, are lacking. We describe conversions between cross-categories of body mass index (BMI) and metabolic health in 786 Swedish twins with up to 27 years of follow-up, from midlife to late-life.

Methods: Metabolic health was defined as the absence of metabolic syndrome (MetS). We first visualized conversions between BMI-metabolic health phenotypes in 100 individuals with measurements available at ages 50–64, 65–79, and ≥80. Next, we modeled conversion in metabolic health status by BMI category in the full sample using Cox proportional hazards regression.

Results: The proportion of individuals with MetS and with overweight or obesity increased with age. However, one-fifth maintained a metabolically healthy overweight or obesity across all three age categories. Among those metabolically healthy at baseline, 59% converted to MetS during follow-up. Conversions occurred 56% more often among individuals with metabolically healthy obesity, but not overweight, compared to normal weight. Among those with MetS at baseline, 60% regained metabolic health during follow-up, with no difference between BMI categories.

Conclusions: Conversions between metabolically healthy and unhealthy status occurred in both directions in all BMI categories. While conversions to MetS were more common among individuals with obesity, many individuals maintained or regained metabolic health during follow-up.

Place, publisher, year, edition, pages
Springer, 2024
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:hj:diva-63035 (URN)10.1038/s41366-023-01425-y (DOI)001112290100002 ()38042933 (PubMedID)2-s2.0-85178490780 (Scopus ID)HOA;intsam;920215 (Local ID)HOA;intsam;920215 (Archive number)HOA;intsam;920215 (OAI)
Funder
NIH (National Institutes of Health), AG04563, AG059329, AG10175, R01 AG060470Swedish Research Council, 2016-03081Forte, Swedish Research Council for Health, Working Life and Welfare, 2018-01201, 2022-00672
Available from: 2023-12-11 Created: 2023-12-11 Last updated: 2024-07-23Bibliographically approved
Womack, S. R., Beam, C. R., Giangrande, E. J., Tong, X., Scharf, R. J., Finkel, D., . . . Turkheimer, E. (2024). Co-recovery of physical size and cognitive ability from infancy to adolescence: A twin study. Child Development, 95(4), 1367-1383
Open this publication in new window or tab >>Co-recovery of physical size and cognitive ability from infancy to adolescence: A twin study
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2024 (English)In: Child Development, ISSN 0009-3920, E-ISSN 1467-8624, Vol. 95, no 4, p. 1367-1383Article in journal (Refereed) Published
Abstract [en]

This study tested phenotypic and biometric associations between physical and cognitive catch-up growth in a community sample of twins (n = 1285, 51.8% female, 89.3% White). Height and weight were measured at up to 17 time points between birth and 15 years, and cognitive ability was assessed at up to 16 time points between 3 months and 15 years. Weight and length at birth were positively associated with cognitive abilities in infancy and adolescence (r's =.16–.51). More rapid weight catch-up growth was associated with slower, steadier cognitive catch-up growth. Shared and nonshared environmental factors accounted for positive associations between physical size at birth and cognitive outcomes. Findings highlight the role of prenatal environmental experiences in physical and cognitive co-development.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
National Category
Psychology
Identifiers
urn:nbn:se:hj:diva-63642 (URN)10.1111/cdev.14079 (DOI)001154724300001 ()38303087 (PubMedID)2-s2.0-85184161750 (Scopus ID)HOA;intsam;938519 (Local ID)HOA;intsam;938519 (Archive number)HOA;intsam;938519 (OAI)
Available from: 2024-02-20 Created: 2024-02-20 Last updated: 2024-07-18Bibliographically approved
Lopes De Oliveira, T., Tang, B., Bai, G., Sjölander, A., Jylhävä, J., Finkel, D., . . . Hägg, S. (2024). Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden. Aging Cell, 23(6), Article ID e14132.
Open this publication in new window or tab >>Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden
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2024 (English)In: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 23, no 6, article id e14132Article in journal (Refereed) Published
Abstract [en]

Antihypertensive, lipid-lowering, and blood glucose-lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow-up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population-based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self-controlled analysis, where each individual is his/her own control, thereby adjusting for all time-stable confounders. The analysis was additionally adjusted for time-varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5-82.8 years at the first in-person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid-modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = -0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid-modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes.

Place, publisher, year, edition, pages
John Wiley & Sons, 2024
Keywords
aging, cognitive function, frailty, medication, physical function
National Category
Gerontology, specialising in Medical and Health Sciences Geriatrics
Identifiers
urn:nbn:se:hj:diva-63819 (URN)10.1111/acel.14132 (DOI)001175791000001 ()38426357 (PubMedID)2-s2.0-85186897246 (Scopus ID)GOA;intsam;942115 (Local ID)GOA;intsam;942115 (Archive number)GOA;intsam;942115 (OAI)
Funder
Swedish Research Council, 2015-03255, 2017-00639, 2019-01272, 2020-06101, 2021-00178, 2022-01608The Karolinska Institutet's Research Foundation
Available from: 2024-03-14 Created: 2024-03-14 Last updated: 2024-08-13Bibliographically approved
Finkel, D., Nilsen, C., Sindi, S. & Kåreholt, I. (2024). Impact of childhood and adult socioeconomic position on change in functional aging. Health Psychology, 43(5), 388-395
Open this publication in new window or tab >>Impact of childhood and adult socioeconomic position on change in functional aging
2024 (English)In: Health Psychology, ISSN 0278-6133, E-ISSN 1930-7810, Vol. 43, no 5, p. 388-395Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To examine life-course models by investigating the roles of childhood and adult socioeconomic position (SEP) in longitudinal changes in a functional aging index.

METHOD: Up to eight waves of testing, covering 25 years, were available from the Swedish Adoption/Twin Study of Aging: N = 654, intake age = 50-82. A two-slope latent growth curve model was applied to the data, and the impact of including childhood and adult SEP as covariates of the intercept (at age 70) and slopes (before and after age 70) was tested.

RESULTS: Both childhood and adult SEP contributed to the best-fitting model. Childhood SEP was significantly associated with intercept and Slope 1 (before age 70) of the latent growth curve model (p < .05). Association of adult SEP with Slope 2 (after age 70) trended toward significance (p < .10). There was a significant interaction effect of childhood and adult SEP on the intercept (p < .05). As a result, intercept at age 70 was highest and change after age 70 was fastest for those whose SEP decreased from childhood to adulthood.

CONCLUSIONS: Both childhood and adult SEP impact change in functional abilities with age, supporting both critical period and social mobility models. The social environment is modifiable by policies at local, national, and international levels, and these policies need to recognize that early social disadvantage can have long-lasting health impacts.

Place, publisher, year, edition, pages
American Psychological Association (APA), 2024
National Category
Public Health, Global Health, Social Medicine and Epidemiology Gerontology, specialising in Medical and Health Sciences
Identifiers
urn:nbn:se:hj:diva-63386 (URN)10.1037/hea0001356 (DOI)001137077200001 ()38190203 (PubMedID)2-s2.0-85190902745 (Scopus ID);intsam;928824 (Local ID);intsam;928824 (Archive number);intsam;928824 (OAI)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 97:0147:1B, 2009-0795Swedish Research Council, 825-2007-7460, 825-2009-6141Axel and Margaret Ax:son Johnson FoundationVårdal FoundationRiksbankens Jubileumsfond
Available from: 2024-01-17 Created: 2024-01-17 Last updated: 2024-05-03Bibliographically approved
Ler, P., Ploner, A., Finkel, D., Reynolds, C. A., Zhan, Y., Jylhava, J., . . . Karlsson, I. K. (2024). Interplay of body mass index and metabolic syndrome: association with physiological age from midlife to late-life. GeroScience, 46, 2605-2617
Open this publication in new window or tab >>Interplay of body mass index and metabolic syndrome: association with physiological age from midlife to late-life
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2024 (English)In: GeroScience, ISSN 2509-2715, Vol. 46, p. 2605-2617Article in journal (Refereed) Published
Abstract [en]

Obesity and metabolic syndrome (MetS) share common pathophysiological characteristics with aging. To better understand their interplay, we examined how body mass index (BMI) and MetS jointly associate with physiological age, and if the associations changed from midlife to late-life. We used longitudinal data from 1,825 Swedish twins. Physiological age was measured as frailty index (FI) and functional aging index (FAI) and modeled independently in linear mixed-effects models adjusted for chronological age, sex, education, and smoking. We assessed curvilinear associations of BMI and chronological age with physiological age, and interactions between BMI, MetS, and chronological age. We found a significant three-way interaction between BMI, MetS, and chronological age on FI (p-interaction = 0<middle dot>006), not FAI. Consequently, we stratified FI analyses by age: < 65, 65-85, and >= 85 years, and modeled FAI across ages. Except for FI at ages >= 85, BMI had U-shaped associations with FI and FAI, where BMI around 26-28 kg/m(2) was associated with the lowest physiological age. MetS was associated with higher FI and FAI, except for FI at ages < 65, and modified the BMI-FI association at ages 65-85 (p-interaction = 0<middle dot>02), whereby the association between higher BMI levels and FI was stronger in individuals with MetS. Age modified the MetS-FI association in ages >= 85, such that it was stronger at higher ages (p-interaction = 0<middle dot>01). Low BMI, high BMI, and metabolic syndrome were associated with higher physiological age, contributing to overall health status among older individuals and potentially accelerating aging.

Place, publisher, year, edition, pages
Springer, 2024
Keywords
Biological age, Frailty index, Metabolic syndrome, Metabolic health, Obesity
National Category
Geriatrics
Identifiers
urn:nbn:se:hj:diva-63221 (URN)10.1007/s11357-023-01032-9 (DOI)001126625000002 ()38102440 (PubMedID)2-s2.0-85179665831 (Scopus ID)HOA;intsam;924951 (Local ID)HOA;intsam;924951 (Archive number)HOA;intsam;924951 (OAI)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2021-00180Swedish Research Council
Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-02-22Bibliographically approved
Finkel, D. & Jaffee, S. R. (2024). Introduction to IDEA Special Issue. Behavior Genetics, 54, 1-3
Open this publication in new window or tab >>Introduction to IDEA Special Issue
2024 (English)In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 54, p. 1-3Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2024
National Category
Psychology Medical Genetics
Identifiers
urn:nbn:se:hj:diva-63190 (URN)10.1007/s10519-023-10173-8 (DOI)38148347 (PubMedID)2-s2.0-85180714728 (Scopus ID)
Available from: 2024-01-04 Created: 2024-01-04 Last updated: 2025-01-12Bibliographically approved
Finkel, D., Kårelind, F., Zarit, S., Bielsten, T., Wijk, H. & Johansson, L. (2024). LATENT CLASSES AND PROGRESSION OF MMSE IN YOUNG-ONSET DEMENTIA: DATA FROM THE SWEDISH DEMENTIA REGISTER. Innovation in Aging, 8(Supplement 1), 527-527
Open this publication in new window or tab >>LATENT CLASSES AND PROGRESSION OF MMSE IN YOUNG-ONSET DEMENTIA: DATA FROM THE SWEDISH DEMENTIA REGISTER
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2024 (English)In: Innovation in Aging, E-ISSN 2399-5300, Vol. 8, no Supplement 1, p. 527-527Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Studies have shown significant heterogeneity in the longitudinal progression of dementia. Growth mixture models have detected up to 4 classes that differ in both baseline Mini-Mental State Exam (MMSE) and rate of decline over time. Most analyses focus on adults over age 65 and investigate group differences in demographic and health variables. The current analysis focused on adults with young onset dementia (YOD) and examined the role of demographic and support variables. Sample included 1025 adults (55% women) registered in the Swedish Dementia Register prior to age 65 with at least 3 registrations. Age at baseline was 38 to 64 (mean=59.3, SD=4.1); follow-up ranged from 1 to 12 years (mean=4.6, SD=2.0). Growth mixture models identified 4 classes: high baseline MMSE and moderate decline over time (56.1%), intermediate baseline MMSE and somewhat faster decline (39.2%), low baseline and stable MMSE over time (3.5%), and high baseline with steep decline (1.2%). Group 2 had the highest proportion Alzheimer’s Disease (AD) diagnosis and Group 4 had the lowest. Group 3 was more likely to have vascular or unspecified dementia and Group 4 was more likely to have vascular or frontotemporal dementia. Groups differed in age at diagnosis (Group 2 youngest), participation in adult daycare (Group 4 most likely), and having home health assistance (Group 2 most likely). Results highlight that YOD is just as heterogeneous as later onset dementia; therefore, it is vital that people with YOD get early diagnosis and a case manager to help identity and meet their individual needs.

Place, publisher, year, edition, pages
Oxford University Press, 2024
National Category
Geriatrics Neurology
Identifiers
urn:nbn:se:hj:diva-67141 (URN)10.1093/geroni/igae098.1723 (DOI)001394198700694 ()HOA;intsam;996357 (Local ID)HOA;intsam;996357 (Archive number)HOA;intsam;996357 (OAI)
Available from: 2025-01-28 Created: 2025-01-28 Last updated: 2025-01-28Bibliographically approved
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