27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-03-06

AUTHORS

Anna Sandebring-Matton, Julen Goikolea, Ingemar Björkhem, Laura Paternain, Nina Kemppainen, Tiina Laatikainen, Tiia Ngandu, Juha Rinne, Hilkka Soininen, Angel Cedazo-Minguez, Alina Solomon, Miia Kivipelto

ABSTRACT

Background27-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.MethodsThe 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.Results27-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.Conclusion27-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 registrationClinicalTrials.gov, NCT01041989. Registered on 4 January 2010 More... »

PAGES

56

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13195-021-00790-y

DOI

http://dx.doi.org/10.1186/s13195-021-00790-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1136164781

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33676572


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23 schema:description Background27-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.MethodsThe 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.Results27-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.Conclusion27-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 registrationClinicalTrials.gov, NCT01041989. Registered on 4 January 2010
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30 schema:keywords AD risk
31 Alzheimer's disease
32 FDG-PET
33 Finnish Geriatric Intervention Study
34 MRI
35 MethodsThe
36 OH reduction
37 PiB-PET
38 Prevent Cognitive Impairment
39 age
40 allocation
41 assessors
42 association
43 baseline
44 brain
45 brain FDG-PET
46 brain MRI
47 changes
48 cholesterol levels
49 cholesterol metabolism
50 cognition
51 cognitive impairment
52 cognitive scores
53 context
54 control group
55 dementia
56 dementia/AD risk
57 disability
58 disease
59 effect
60 effect modifiers
61 finger
62 general population
63 gray matter
64 group
65 group allocation
66 hippocampal volume
67 humans
68 hypercholesterolemia
69 impairment
70 improvement
71 individuals
72 intervention
73 intervention studies
74 levels
75 linear regression models
76 link
77 longitudinal associations
78 lower cognitive scores
79 lower total gray matter
80 markers
81 matter
82 measures
83 metabolism
84 missing link
85 model
86 modifiers
87 multidomain intervention
88 older individuals
89 outcome assessors
90 oxysterols
91 participants
92 population
93 potential missing link
94 preventive interventions
95 ratio
96 reduction
97 regression models
98 relation
99 risk
100 scores
101 sex
102 study
103 substantial cognitive impairment
104 total cholesterol levels
105 total gray matter
106 trials
107 volume
108 younger age
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