Alina Solomon1,2,3, Miia Kivipelto1,4,3,5, Anna Sandebring-Matton6,7, Julen Goikolea8, Ingemar Björkhem9, Laura Paternain8, Nina Kemppainen10,11, Tiina Laatikainen4,12,13, Tiia Ngandu1,13, Juha Rinne11, Hilkka Soininen2,14, Angel Cedazo-Minguez8. 1. Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden. 2. Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland. 3. Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK. 4. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 5. Theme Aging, Karolinska University Hospital, Stockholm, Sweden. 6. Division of Neurogeriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden. anna.matton@ki.se. 7. Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden. anna.matton@ki.se. 8. Division of Neurogeriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden. 9. Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska University Hospital, Stockholm, Sweden. 10. Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland. 11. Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland. 12. Joint Municipal Authority for North Karelia Social and Health Services, Joensuu, Finland. 13. Public Health Promotion Unit, Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland. 14. Neurocenter, Neurology Kuopio University Hospital, Kuopio, Finland.
Abstract
BACKGROUND:27-Hydroxycholesterol (27-OH), the main circulating oxysterol in humans and the potential missing link between peripheral hypercholesterolemia and Alzheimer's disease (AD), has not been investigated previously in relation to cognition and neuroimaging markers in the context of preventive interventions. METHODS: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older individuals (60-77 years) at increased risk for dementia but without dementia or substantial cognitive impairment from the general population. Participants were randomized to a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice) in a 1:1 ratio. Outcome assessors were masked to group allocation. This FINGER exploratory sub-study included 47 participants with measures of 27-OH, cognition, brain MRI, brain FDG-PET, and PiB-PET. Linear regression models were used to assess the cross-sectional and longitudinal associations between 27-OH, cognition, and neuroimaging markers, considering several potential confounders/intervention effect modifiers. RESULTS:27-OH reduction during the intervention was associated with improvement in cognition (especially memory). This was not observed in the control group. The intervention reduced 27-OH particularly in individuals with the highest 27-OH levels and younger age. No associations were found between changes in 27-OH levels and neuroimaging markers. However, at baseline, a higher 27-OH was associated with lower total gray matter and hippocampal volume, and lower cognitive scores. These associations were unaffected by total cholesterol levels. While sex seemed to influence associations at baseline, it did not affect longitudinal associations. CONCLUSION: 27-OH appears to be a marker not only for dementia/AD risk, but also for monitoring the effects of preventive interventions on cholesterol metabolism. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01041989 . Registered on 4 January 2010.
RCT Entities:
BACKGROUND:27-Hydroxycholesterol (27-OH), the main circulating oxysterol in humans and the potential missing link between peripheral hypercholesterolemia and Alzheimer's disease (AD), has not been investigated previously in relation to cognition and neuroimaging markers in the context of preventive interventions. METHODS: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older individuals (60-77 years) at increased risk for dementia but without dementia or substantial cognitive impairment from the general population. Participants were randomized to a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice) in a 1:1 ratio. Outcome assessors were masked to group allocation. This FINGER exploratory sub-study included 47 participants with measures of 27-OH, cognition, brain MRI, brain FDG-PET, and PiB-PET. Linear regression models were used to assess the cross-sectional and longitudinal associations between 27-OH, cognition, and neuroimaging markers, considering several potential confounders/intervention effect modifiers. RESULTS:27-OH reduction during the intervention was associated with improvement in cognition (especially memory). This was not observed in the control group. The intervention reduced 27-OH particularly in individuals with the highest 27-OH levels and younger age. No associations were found between changes in 27-OH levels and neuroimaging markers. However, at baseline, a higher 27-OH was associated with lower total gray matter and hippocampal volume, and lower cognitive scores. These associations were unaffected by total cholesterol levels. While sex seemed to influence associations at baseline, it did not affect longitudinal associations. CONCLUSION:27-OH appears to be a marker not only for dementia/AD risk, but also for monitoring the effects of preventive interventions on cholesterol metabolism. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01041989 . Registered on 4 January 2010.
Authors: Nina Kemppainen; Jarkko Johansson; Jarmo Teuho; Riitta Parkkola; Juho Joutsa; Tiia Ngandu; Alina Solomon; Ruth Stephen; Yawu Liu; Tuomo Hänninen; Teemu Paajanen; Tiina Laatikainen; Hilkka Soininen; Antti Jula; Johanna Rokka; Eero Rissanen; Tero Vahlberg; Julia Peltoniemi; Miia Kivipelto; Juha O Rinne Journal: Neurology Date: 2017-12-20 Impact factor: 9.910
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