@article{Lourida2019,
title = {Association of Lifestyle and Genetic Risk With Incidence of Dementia},
author = {I Lourida and E Hannon and TJ Littlejohns and KM Langa and E Hyppönen and E Kuzma and DJ Llewellyn },
url = {https://www.ncbi.nlm.nih.gov/pubmed/31302669},
year = {2019},
date = {2019-07-14},
journal = {JAMA},
abstract = {Importance:
Genetic factors increase risk of dementia, but the extent to which this can be offset by lifestyle factors is unknown.

Objective:
To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk.

Design, Setting, and Participants:
A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017.

Exposures:
A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles.

Main Outcomes and Measures:
Incident all-cause dementia, ascertained through hospital inpatient and death records.

Results:
A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]).

Conclusions and Relevance:
Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.},
keywords = {9462, dementia, featured, genetics},
pubstate = {published},
tppubtype = {article}
}

@article{Maddock2017,
title = {Vitamin D and cognitive function: A Mendelian randomisation study},
author = {Jane Maddock and Ang Zhou and Alana Cavadino and Elżbieta Kuźma and Yanchun Bao and Melissa C Smart and Kai-Uwe Saum and Ben Schöttker and Jorgen Engmann and Marie Kjærgaard and Ville Karhunen and Yiqiang Zhan and Terho Lehtimäki and Suvi P Rovio and Liisa Byberg and Jari Lahti and Pedro Marques-Vidal and Abhijit Sen and Laura Perna and Henrik Schirmer and Archana Singh-Manoux and Juha Auvinen and Nina Hutri-Kähönen and Mika Kähönen and Lena Kilander and Katri Räikkönen and Håkan Melhus and Erik Ingelsson and Idris Guessous and Katja E Petrovic and Helena Schmidt and Reinhold Schmidt and Peter Vollenweider and Lars Lind and Johan G Eriksson and Karl Michaëlsson and Olli T Raitakari and Sara Hägg and Nancy L Pedersen and Karl-Heinz Herzig and Marjo-Riitta Järvelin and Juha Veijola and Mika Kivimaki and Rolf Jorde and Hermann Brenner and Meena Kumari and Chris Power and David J Llewellyn and Elina Hyppönen},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643555/},
year = {2017},
date = {2017-10-16},
journal = {Scientific Reports},
abstract = {The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.},
keywords = {9462, Cognitive Function, genetics, vitamin D},
pubstate = {published},
tppubtype = {article}
}