Randomized Controlled Trial

. 2025 Nov;21(11):e70888.

doi: 10.1002/alz.70888.

Identifying dementia risk profiles for targeted interventions: A latent class analysis of at-risk middle-aged Australians

Muhammad Rehan Sarwar¹, Amanda J Cross¹, Kali Godbee¹, Gopisankar Mohanannair Geethadevi¹, Parker Magin^{2

3}, Mary Tullipan¹, Amanda L Baker⁴, Billie Bonevski⁵, Stephanie A Ward^{6

7}, Ajay Mahal⁸, Vincent Versace⁹, J Simon Bell¹, Kevin Mc Namara^{1

9}, Sharleen L O'Reilly^{10

11}, Dennis Thomas^{12

13}, Elizabeth Manias¹⁴, Kaarin J Anstey^{15

16}, Marlien Varnfield¹⁷, Rajiv Jayasena¹⁸, Rohan A Elliott^{1

19}, Cik Y Lee^{1

20}, Andrea Hernan⁹, Denise van den Bosch¹, Catherine Ferreira²¹, Johnson George^{1

7}

Affiliations

¹ Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
² School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia.
³ School of Population Health, University of New South Wales, Sydney, New South Wales, Australia.
⁴ National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia.
⁶ Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
⁷ School of Public Health and Preventive Medicine, Faculty of Medicine Nursing and Health Sciences, Monash University, St Kilda, Victoria, Australia.
⁸ Nossal Institute for Global Health, University of Melbourne, Melbourne, Victoria, Australia.
⁹ Deakin Rural Health, Faculty of Health, Deakin University, Warrnambool, Victoria, Australia.
¹⁰ School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
¹¹ School of Exercise and Nutrition Science, Deakin University, Melbourne, Victoria, Australia.
¹² Centre of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, New South Wales, Australia.
¹³ Asthma and Breathing Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
¹⁴ Monash Nursing and Midwifery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
¹⁵ School of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
¹⁶ UNSW Ageing Futures Institute, University of New South Wales, Sydney, New South Wales, Australia.
¹⁷ The Australian e-Health Research Centre, Health and Biosecurity, CSIRO, Herston, Queensland, Australia.
¹⁸ The Australian e-Health Research Centre, Health and Biosecurity, CSIRO, Parkville, Victoria, Australia.
¹⁹ Pharmacy Department, Austin Health, Heidelberg, Victoria, Australia.
²⁰ Department of Nursing, School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
²¹ North Western Melbourne Primary Health Network, Docklands, Victoria, Australia.

PMID: 41200791
PMCID: PMC12592938
DOI: 10.1002/alz.70888

Randomized Controlled Trial

Identifying dementia risk profiles for targeted interventions: A latent class analysis of at-risk middle-aged Australians

Muhammad Rehan Sarwar et al. Alzheimers Dement. 2025 Nov.

. 2025 Nov;21(11):e70888.

doi: 10.1002/alz.70888.

Authors

Affiliations

¹ Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
² School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia.
³ School of Population Health, University of New South Wales, Sydney, New South Wales, Australia.
⁴ National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia.
⁵ Flinders Health and Medical Research Institute, Flinders University, Bedford Park, South Australia, Australia.
⁶ Centre for Healthy Brain Ageing, University of New South Wales, Sydney, New South Wales, Australia.
⁷ School of Public Health and Preventive Medicine, Faculty of Medicine Nursing and Health Sciences, Monash University, St Kilda, Victoria, Australia.
⁸ Nossal Institute for Global Health, University of Melbourne, Melbourne, Victoria, Australia.
⁹ Deakin Rural Health, Faculty of Health, Deakin University, Warrnambool, Victoria, Australia.
¹⁰ School of Agriculture and Food Science, University College Dublin, Dublin, Ireland.
¹¹ School of Exercise and Nutrition Science, Deakin University, Melbourne, Victoria, Australia.
¹² Centre of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, New South Wales, Australia.
¹³ Asthma and Breathing Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
¹⁴ Monash Nursing and Midwifery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
¹⁵ School of Psychology, University of New South Wales, Sydney, New South Wales, Australia.
¹⁶ UNSW Ageing Futures Institute, University of New South Wales, Sydney, New South Wales, Australia.
¹⁷ The Australian e-Health Research Centre, Health and Biosecurity, CSIRO, Herston, Queensland, Australia.
¹⁸ The Australian e-Health Research Centre, Health and Biosecurity, CSIRO, Parkville, Victoria, Australia.
¹⁹ Pharmacy Department, Austin Health, Heidelberg, Victoria, Australia.
²⁰ Department of Nursing, School of Health Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
²¹ North Western Melbourne Primary Health Network, Docklands, Victoria, Australia.

PMID: 41200791
PMCID: PMC12592938
DOI: 10.1002/alz.70888

Abstract

Introduction: This study aimed to identify distinct dementia risk profiles in middle-aged adults with two or more potential dementia risk factors, to inform targeted prevention strategies.

Methods: Cross-sectional analysis of baseline sociodemographic, clinical, and dementia-risk data from the HAPPI MIND trial. Dementia risk was assessed using the Australian National University Alzheimer's Disease Risk Index. Risk profiles were identified using latent class analysis (LCA).

Results: Among 403 participants (mean age 56.4 ± 5.7 years, 62.5% female), the median number of dementia risk factors was 5.0; hyperlipidaemia (92.5%), low cognitive activity (72.5%), obesity (57.6%), and hypertension (52.7%) were the most prevalent. Several risk factors showed significant positive correlations. LCA identified three distinct classes: 1-High Cardiometabolic Burden; 2-High Behavioural and Psychosocial Risk; and 3-Low Risk with Healthy Behaviours.

Discussion: The identified latent classes highlight heterogeneity of dementia risk profile in midlife. Tailored, multidomain interventions addressing each group's specific needs may improve dementia risk profiles and support broader health outcomes.

Highlights: Middle-aged Australians who participated in the HAPPI MIND dementia risk reduction trial had a median of five modifiable risk factors. Significant positive correlations were observed between behavioral and clinical risk factors, such as depression, along with poor diet, social isolation, and smoking. Latent class analysis revealed three distinct profiles: High Cardiometabolic Burden; High Behavioral and Psychosocial Risk; and Low Risk with Healthy Behaviors. The findings suggest there is a need for personalized, multidomain prevention strategies tailored to individual risk profiles in primary care.

Keywords: ANU‐ADRI; dementia; latent class analysis; middle‐aged adults; modifiable risk factors; multidomain interventions; primary care.

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Conflict of interest statement

A.J.C. is supported by a National Health and Medical Research Council (NHMRC) emerging leadership 1 grant (APP2009633) and has received grant funding or consulting funding from the Medical Research Future Fund, NHMRC, Dementia Australia Research Foundation and the Pharmaceutical Society of Australia. All funds were paid to the employing institution. A.J.C. also declares she is a national board director for the Pharmaceutical Society of Australia. A.L.B. was supported by an NHMRC Fellowship (APP1135901, 2018‐2022). V.V. is funded by the Rural Health Multidisciplinary Training Program. J.S.B. has received grant funding or consulting funds from the National Health and Medical Research Council, Medical Research Future Fund, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, GlaxoSmithKline Supported Studies Programme, Amgen and several aged care provider organisations unrelated to this work. All grants and consulting funds were paid to the employing institution. D.T. has received grant funding from GlaxoSmithKline, unrelated to this work and paid to his employer. K.J.A. is funded by ARC Laureate Fellowship (FL19010001). J.G. has received honoraria from GlaxoSmithKline, AstraZeneca and Pfizer for consultancy and educational/research grants from Boehringer‐Ingelheim, GlaxoSmithKline and Pfizer for unrelated projects, all of which have been paid to his employer. All other authors declare no competing interests. Author disclosures are available in the Supporting Information.

Figures

**FIGURE 1**
Estimated probabilities of risk factors across latent classes.

See this image and copyright information in PMC

References

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1. Song S, Stern Y, Gu Y. Modifiable lifestyle factors and cognitive reserve: a systematic review of current evidence. Ageing Res Rev. 2022;74:101551. - PMC - PubMed
1. Anstey KJ, Ee N, Eramudugolla R, Jagger C, Peters R. A systematic review of meta‐analyses that evaluate risk factors for dementia to evaluate the quantity, quality, and global representativeness of evidence. J Alzheimers Dis. 2019;70(s1):S165‐S186. - PMC - PubMed
1. Gong J, Harris K, Lipnicki DM, et al. Sex differences in dementia risk and risk factors: individual‐participant data analysis using 21 cohorts across six continents from the COSMIC consortium. Alzheimers Dement. 2023;19(8):3365‐3378. - PMC - PubMed
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Identifying dementia risk profiles for targeted interventions: A latent class analysis of at-risk middle-aged Australians

Affiliations

Identifying dementia risk profiles for targeted interventions: A latent class analysis of at-risk middle-aged Australians

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials