No abstract

The FINGER intervention was beneficial regardless of participants' characteristics and can thus be implemented in a large elderly population at increased risk for dementia.

Twin studies suggest that both disc degeneration and back pain have a genetic component. We were interested in estimating the heritability of low back pain in men and examining whether genetic influences on back pain are mediated through genetic influences on disc degeneration. Thus, we conducted a classic twin study with multivariate quantitative genetic models to estimate the degree to which genetic (or environmental) effects on back pain were correlated with genetic (or environmental) effects on disc degeneration. Subjects included 147 monozygotic and 153 dizygotic male twin pairs (N=600 subjects) from the population-based Finnish Twin Cohort. All subjects underwent lumbar magnetic resonance imaging and completed an extensive interview, including back pain history and exposure to suspected risk factors. Disc height narrowing was the degenerative finding most associated with pain history, and was used to index disc degeneration in the models. Statistically significant genetic correlations were found for disc height narrowing and different definitions of back pain, such as duration of the worst back pain episode (r(g)=0.46) and hospitalization for back problems (r(g)=0.49), as well as disability in the previous year from back pain (r(g)=0.33). The heritability estimates for these back pain variables ranged from 30% to 46%. There also were statistically significant, but weaker, environmental correlations for disc height narrowing with back symptoms over the prior year. A substantial minority of the genetic influences on pain was due to the same genetic influences affecting disc degeneration. This suggests that disc degeneration is one pathway through which genes influence back pain.

The role of the apolipoprotein E (APOE) ε4 allele as an effect modifier in lifestyle interventions to prevent cognitive impairment is still unclear. OBJECTIVE To examine whether the APOE ε4 allele modifies the previously reported significant cognitive benefits of a multidomain lifestyle intervention (prespecified subgroup analysis). DESIGN, SETTING, AND PARTICIPANTS The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a randomized clinical trial in 6 centers across Finland (screening and randomization performed from September 7, 2009, through November 24, 2011; intervention duration, 2 years). Data analysis was performed from August 1, 2015, to March 31, 2016. The study population was at-risk older individuals from the general population. Inclusion criteria were age of 60 to 77 years; Cardiovascular Risk Factors, Aging, and Dementia risk score of at least 6 points; and cognition at a mean level or slightly lower than expected for age. Individuals with dementia or substantial cognitive impairment and conditions that prevented cooperation or safe engagement in the intervention were excluded. APOE genotype data were available for 1175 of the 1260 participants. INTERVENTIONS Participants were randomly assigned in a 1:1 ratio to a multidomain intervention group (diet, exercise, cognitive training, and vascular risk management) or a control group (general health advice). Group allocation was not actively disclosed to participants, and outcome assessors were masked to group allocation. MAIN OUTCOMES AND MEASURES Primary outcome was change in cognition measured through a comprehensive neuropsychological test battery. Analysis was based on modified intention to treat (participants with at least 1 postbaseline assessment). RESULTS A total of 1109 participants (mean [SD] age, 69.3 [4.7] years; 514 [46.3%] female) were included in the analysis: 362 APOE ε4 allele carriers (173 intervention and 189 control) and 747 noncarriers (380 intervention and 367 control). The APOE ε4 carriers and noncarriers were not significantly different at baseline (except for serum cholesterol level). The difference between the intervention and control groups in annual neuropsychological test battery total score change was 0.037 (95% CI, 0.001 to 0.073) among carriers and 0.014 (95% CI, −0.011 to 0.039) among noncarriers. Intervention effect was not significantly different between carriers and noncarriers (0.023; 95% CI, −0.021 to 0.067). CONCLUSIONS AND RELEVANCE Healthy lifestyle changes may be beneficial for cognition in older at-risk individuals even in the presence of APOE-related genetic susceptibility to dementia. Whether such benefits are more pronounced in APOE ε4 carriers compared with noncarriers should be further investigated. The findings also emphasize the importance of early prevention strategies that target multiple modifiable risk factors simultaneously.

IMPORTANCE Although guidelines for vitamin D supplementation in infants have been widely implemented, they are mostly based on studies focusing on prevention of rickets. The optimal dose for bone strength and infection prevention in healthy infants remains unclear. OBJECTIVE To determine whether daily supplementation with 1200 IU of vitamin D 3 increases bone strength or decreases incidence of infections in the first 2 years of life compared with a dosage of 400 IU/d. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial involving a random sample of 975 healthy term infants at a maternity hospital in Helsinki, Finland. Study recruitment occurred between January 14, 2013, and June 9, 2014, and the last follow-up was May 30, 2016. Data analysis was by the intention-to-treat principle. INTERVENTIONS Randomization of 489 infants to daily oral vitamin D 3 supplementation of 400 IU and 486 infants to 1200 IU from age 2 weeks to 24 months. MAIN OUTCOMES AND MEASURES Primary outcomes were bone strength and incidence of parent-reported infections at 24 months. RESULTS Of the 975 infants who were randomized, 485 (49.7%) were girls and all were of Northern European ethnicity. Eight hundred twenty-three (84.4%) completed the 24-month follow-up. We found no differences between groups in bone strength measures, including bone mineral content (mean difference, 0.4 mg/mm; 95% CI, −0.8 to 1.6), mineral density (mean difference, 2.9 mg/cm 3 ; 95% CI, −8.3 to 14.2), cross-sectional area (mean difference,-0.9 mm 2 ; 95% CI, −5.0 to 3.2), or polar moment of inertia (mean difference,-66.0 mm 4 , 95% CI, −274.3 to 142.3). Incidence rates of parent-reported infections did not differ between groups (incidence rate ratio, 1.00; 95% CI, 0.93-1.06). At birth, 914 of 955 infants (95.7%) were vitamin D sufficient (ie, 25-hydroxyvitamin D [25(OH)D] concentration Ն20.03 ng/mL). At 24 months, mean 25(OH)D concentration was higher in the 1200-IU group than in the 400-IU group (mean difference, 12.50 ng/mL; 95% CI, 11.22-13.78). CONCLUSIONS AND RELEVANCE A vitamin D 3 supplemental dose of up to 1200 IU in infants did not lead to increased bone strength or to decreased infection incidence. Daily supplementation with 400 IU vitamin D 3 seems adequate in maintaining vitamin D sufficiency in children younger than 2 years.

No abstract

Late-life heart diseases increase the subsequent risk of dementia and AD. Prevention and effective treatment of heart diseases may be important also from the perspective of brain health and cognitive functioning.

Objective. To examine the allelic diversity of structural, inflammatory, and matrix-modifying gene candidates and their association with disc degeneration.Methods. Subjects were 588 men ages 35-70 years. We investigated associations of single-nucleotide polymorphisms in AGC1 and in 12 collagen, 8 interleukin, and 4 matrix metalloproteinase genes with quantitative magnetic resonance imaging measurements of disc desiccation and disc bulging and height narrowing scores, after controlling for age and suspected risk factors. Analyses were performed using QTDT software. P values were derived from 1,000 permutations, and empirical P values for global significance also were applied.Results. Twelve of the 99 variants in 25 selected candidate genes provided evidence of association (P < 0.05) with disc signal intensity in the upper and/or lower lumbar regions. Allelic variants of AGC1 (rs1042631; P ‫؍‬ 0.001), COL1A1 (rs2075555; P ‫؍‬ 0.005), COL9A1 (rs696990; P ‫؍‬ 0.00008), and COL11A2 (rs2076311; P ‫؍‬ 0.018) genes provided the most significant evidence of association with disc signal intensity. The same variants of AGC1 (P ‫؍‬ 0.010) and COL9A1 (P ‫؍‬ 0.014), as well as variants in the COL11A1 gene (rs1463035 [P ‫؍‬ 0.004]; rs1337185 [P ‫؍‬ 0.015]) were also associated with disc bulging, as was AGC1 with disc height narrowing (rs1516797; P ‫؍‬ 0.005). In addition, 4 allelic variants in the immunologic candidate genes (rs2071375 in IL1A [P ‫؍‬ 0.027]; rs1420100 in IL18RAP [P ‫؍‬ 0.005]) were associated with disc signal intensity.Conclusion. Genetic variants account for interindividual differences in disc matrix synthesis and degradation. The accuracy of the quantitative disc signal intensity measurements we used likely enhanced our ability to observe these associations. Our findings shed light on possible mechanisms of degeneration and support the view that disc degeneration is a polygenetic condition.Intervertebral disc degeneration is a suspected cause of common back pain (1), but both the etiology and pathogenesis of disc degeneration are poorly understood (2). A 1992 review of relevant scientific literature identified physical demands of occupational and leisure activities as primary risk factors, while the role of genetics was uncertain (3). However, results from later twin studies suggested that heredity plays a major role, accounting for an estimated 34-74% of variance in disc degeneration (4,5).