Ruth Peters1,2, Ying Xu1,2, Riitta Antikainen3, Nigel Beckett4, Jacobijn Gussekloo5, Carol Jagger6, Johan Wouter Jukema7,8, Sirkka Keinanen-Kiukaanniemi3, Lina Rydén9,10, Ingmar Skoog9, Jan A Staessen11,12, Lutgarde Thijs13, Stella Trompet5, Philip J Tully14,15, Christophe Tzourio15, Kaarin J Anstey1,2. 1. Neuroscience Research Australia, Sydney, New South Wales, Australia. 2. School of Psychology, University of New South Wales, Sydney, New South Wales, Australia. 3. Faculty of Medicine, Oulu University, Oulu, Finland. 4. Guys and St Thomas' NHS Trust, London, United Kingdom. 5. Leiden University Medical Center, Leiden, The Netherlands. 6. Faculty of Medical Sciences, University of Newcastle, Newcastle upon Tyne, United Kingdom. 7. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 8. Netherlands Heart Institute, Utrecht, The Netherlands. 9. Institute of Neuroscience and Physiology, Sahlgrenska Academy, Centre for Ageing and Health (AgeCap) at the University of Gothenburg, Gothenburg, Sweden. 10. Department of Psychiatry Cognition and Old Age Psychiatry, Sahlgrenska University Hospital, Region Västra Götaland, Mölndal, Sweden. 11. Research Institute Alliance for the Promotion of Preventive Medicine, Mechelen, Belgium. 12. Biomedical Sciences Group, Faculty of Medicine, University of Leuven, Leuven, Belgium. 13. Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium. 14. Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia. 15. Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France.
Abstract
INTRODUCTION: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. METHOD: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. RESULTS: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. CONCLUSION: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.
INTRODUCTION: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. METHOD: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. RESULTS: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. CONCLUSION: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.