Carotid intimamedia thickness in patients with severe hypertriglyceridemia.

Background and aims: Severe hypertriglyceridemia (HTG), defined as plasma triglyceride (TG) concentration > 10 mmol/L, is relatively uncommon, and its implications for atherosclerotic cardiovascular disease (ASCVD) risk remain somewhat unclear. We evaluated the association between severe HTG and carotid intima-media thickness (IMT), a marker for ASCVD. Methods: We studied three clinical cohorts: 88 patients with severe HTG (mean TG level 20.6 mmol/L), 271 patients with familial hypercholesterolemia (FH) as a contrast group, and 70 normolipidemic controls. Carotid IMT was measured using standardized ultrasound imaging. Statistical analysis was conducted using one-way analysis of variance (ANOVA) to compare mean IMT values, analysis of covariance (ANCOVA) to adjust for confounding variables, specifically age and sex, as well as Spearman pairwise correlation analysis between variables. Results: Unadjusted mean carotid IMT was greater in severe HTG and FH groups compared to controls, however, this was no longer significant for severe HTG after adjustment for age and sex. In contrast, adjusted carotid IMT remained significantly different between the FH and control groups. Conclusions: Our findings suggest that extreme TG elevations in severe HTG patients are not significantly associated with carotid IMT, in contrast to the increased IMT seen in FH patients. These findings add perspective to the complex relationship between severe HTG and ASCVD risk.

Is white matter hyperintensity burden associated with cognitive and motor impairment in patients with parkinson's disease? A systematic review and meta-analysis.

White matter damage quantified as white matter hyperintensities (WMH) may aggravate cognitive and motor impairments, but whether and how WMH burden impacts these problems in Parkinson's disease (PD) is not fully understood. This study aimed to examine the association between WMH and cognitive and motor performance in PD through a systematic review and meta-analysis. We compared the WMH burden across the cognitive spectrum (cognitively normal, mild cognitive impairment, dementia) in PD including controls. Motor signs were compared in PD with low/negative and high/positive WMH burden. We compared baseline WMH burden of PD who did and did not convert to MCI or dementia. MEDLINE and EMBASE databases were used to conduct the literature search resulting in 50 studies included for data extraction. Increased WMH burden was found in individuals with PD compared with individuals without PD (i.e. control) and across the cognitive spectrum in PD (i.e. PD, PD-MCI, PDD). Individuals with PD with high/positive WMH burden had worse global cognition, executive function, and attention. Similarly, PD with high/positive WMH presented worse motor signs compared with individuals presenting low/negative WMH burden. Only three longitudinal studies were retrieved from our search and they showed that PD who converted to MCI or dementia, did not have significantly higher WMH burden at baseline, although no data was provided on WMH burden changes during the follow up. We conclude, based on cross-sectional studies, that WMH burden appears to increase with PD worse cognitive and motor status in PD.

Prevention of Falls in Parkinson's Disease: Guidelines and Gaps.

Background: People living with Parkinson's disease (PD) have a high risk for falls. Objective: To examine gaps in falls prevention targeting people with PD as part of the Task Force on Global Guidelines for Falls in Older Adults. Methods: A Delphi consensus process was used to identify specific recommendations for falls in PD. The current narrative review was conducted as educational background with a view to identifying gaps in fall prevention. Results: A recent Cochrane review recommended exercises and structured physical activities for PD; however, the types of exercises and activities to recommend and PD subgroups likely to benefit require further consideration. Freezing of gait, reduced gait speed, and a prior history of falls are risk factors for falls in PD and should be incorporated in assessments to identify fall risk and target interventions. Multimodal and multi-domain fall prevention interventions may be beneficial. With advanced or complex PD, balance and strength training should be administered under supervision. Medications, particularly cholinesterase inhibitors, show promise for falls prevention. Identifying how to engage people with PD, their families, and health professionals in falls education and implementation remains a challenge. Barriers to the prevention of falls occur at individual, environmental, policy, and health system levels. Conclusion: Effective mitigation of fall risk requires specific targeting and strategies to reduce this debilitating and common problem in PD. While exercise is recommended, the types and modalities of exercise and how to combine them as interventions for different PD subgroups (cognitive impairment, freezing, advanced disease) need further study.

Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years.

Diabetes medications may modify the risk of certain cancers. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 for studies evaluating associations between diabetes medications and the risk of breast, lung, colorectal, prostate, liver, and pancreatic cancers. A total of 92 studies (3 randomized controlled trials, 64 cohort studies, and 25 case-control studies) were identified in the systematic review, involving 171 million participants. Inverse relationships with colorectal (n = 18; RR = 0.85; 95% CI = 0.78-0.92) and liver cancers (n = 10; RR = 0.55; 95% CI = 0.46-0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (n = 6; RR = 0.87; 95% CI = 0.80-0.95), lung (n = 6; RR = 0.77; 95% CI = 0.61-0.96) and liver (n = 8; RR = 0.83; 95% CI = 0.72-0.95) cancers. Insulins were negatively associated with breast (n = 15; RR = 0.90; 95% CI = 0.82-0.98) and prostate cancer risks (n = 7; RR = 0.74; 95% CI = 0.56-0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (n = 5; RR = 1.26; 95% CI = 1.01-1.57), and between insulins and liver (n = 7; RR = 1.74; 95% CI = 1.08-2.80) and pancreatic cancers (n = 8; RR = 2.41; 95% CI = 1.08-5.36). Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk.

Effects of Exercise Alone or Combined With Cognitive Training and Vitamin D Supplementation to Improve Cognition in Adults With Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Exercise, cognitive training, and vitamin D may enhance cognition in older adults with mild cognitive impairment (MCI). Objective: To determine whether aerobic-resistance exercises would improve cognition relative to an active control and if a multidomain intervention including exercises, computerized cognitive training, and vitamin D supplementation would show greater improvements than exercise alone. Design, Setting, and Participants: This randomized clinical trial (the SYNERGIC Study) was a multisite, double-masked, fractional factorial trial that evaluated the effects of aerobic-resistance exercise, computerized cognitive training, and vitamin D on cognition. Eligible participants were between ages 65 and 84 years with MCI enrolled from September 19, 2016, to April 7, 2020. Data were analyzed from February 2021 to December 2022. Interventions: Participants were randomized to 5 study arms and treated for 20 weeks: arm 1 (multidomain intervention with exercise, cognitive training, and vitamin D), arm 2 (exercise, cognitive training, and placebo vitamin D), arm 3 (exercise, sham cognitive training, and vitamin D), arm 4 (exercise, sham cognitive training, and placebo vitamin D), and arm 5 (control group with balance-toning exercise, sham cognitive training, and placebo vitamin D). The vitamin D regimen was a 10 000 IU dose 3 times weekly. Main Outcomes and Measures: Primary outcomes were changes in ADAS-Cog-13 and Plus variant at 6 months. Results: Among 175 randomized participants (mean [SD] age, 73.1 [6.6] years; 86 [49.1%] women), 144 (82%) completed the intervention and 133 (76%) completed the follow-up (month 12). At 6 months, all active arms (ie, arms 1 through 4) with aerobic-resistance exercise regardless of the addition of cognitive training or vitamin D, improved ADAS-Cog-13 when compared with control (mean difference, -1.79 points; 95% CI, -3.27 to -0.31 points; P = .02; d = 0.64). Compared with exercise alone (arms 3 and 4), exercise and cognitive training (arms 1 and 2) improved the ADAS-Cog-13 (mean difference, -1.45 points; 95% CI, -2.70 to -0.21 points; P = .02; d = 0.39). No significant improvement was found with vitamin D. Finally, the multidomain intervention (arm 1) improved the ADAS-Cog-13 score significantly compared with control (mean difference, -2.64 points; 95% CI, -4.42 to -0.80 points; P = .005; d = 0.71). Changes in ADAS-Cog-Plus were not significant. Conclusions and Relevance: In this clinical trial, older adults with MCI receiving aerobic-resistance exercises with sequential computerized cognitive training significantly improved cognition, although some results were inconsistent. Vitamin D supplementation had no effect. Our findings suggest that this multidomain intervention may improve cognition and potentially delay dementia onset in MCI. Trial Registration: ClinicalTrials.gov Identifier: NCT02808676.

Involvement of Informal Caregivers in Preventing Falls in Older Adults with Cognitive Impairment: A Rapid Review.

BACKGROUND: The prevalence of falls and related injuries is double in older adults with cognitive impairment compared with cognitively healthy older adults. A growing body of literature shows that falls prevention interventions in the cognitively impaired are difficult to implement and that the feasibility and adherence to interventions depend on a number of factors including informal caregiver involvement. However, no systematic review exists on the topic. OBJECTIVE: Our objective is to determine whether involvement of informal caregivers can reduce falls in older adults with cognitive impairment. METHODS: Rapid review following Cochrane collaboration guidelines. RESULTS: Seven randomized controlled trials were identified involving 2,202 participants. We identified the following areas where informal caregiving may have an important role in fall prevention in older adults with cognitive impairment: 1) enhancing adherence to the exercise program; 2) identifying and recording falls incidents and circumstances; 3) identifying and modifying possible environmental falls risk factors inside patient's home; and 4) playing an active role in modifying lifestyle in terms of diet/nutrition, limiting antipsychotics, and avoiding movements risking falls. However, informal caregiver involvement was identified as an incidental finding in these studies and the level of evidence ranged from low to moderate. CONCLUSION: Informal caregiver involvement in planning and delivering interventions to reduce falls has been found to increase the adherence of individuals with cognitive impairment in falls prevention programs. Future research should address whether involvement of informal caregivers may improve efficacy of prevention programs by reducing the number of falls as a primary outcome.

Multidomain trials to prevent dementia: addressing methodological challenges.

BACKGROUND: Multidomain trials to prevent dementia by simultaneously targeting multiple risk factors with non-pharmacological lifestyle interventions show promise. Designing trials to evaluate the efficacy of individual interventions and their combinations is methodologically challenging. Determining the efficacy is, nevertheless, important to individuals, payers, and for resource allocations to support intervention implementation. MAIN BODY: The central rationale for seminal trials improving cardiovascular health or reducing falls risk in older adults is that multifactorial conditions may be amenable to improvement by simultaneously targeting multiple modifiable risk factors. Similar reasoning underlies lifestyle interventions to reduce dementia risk using combinations of physical exercise, cognitive training, diet, amelioration of vascular-metabolic risk factors, and improving sleep quality. Randomizing individuals with at least two modifiable risk factors to "standardly tailored" interventions to mitigate their risk factors, versus a comparator arm, will yield an unbiased estimate of the cumulative average effect of modifying more versus fewer risk factors. The between-group difference in the cognitive primary outcome will reflect both the main effects of the mitigated risk factors, as well as their synergistic effects. However, given the positive trial results, there are inherent challenges in quantifying post hoc which components, or combination of components, were responsible for improvements in cognition. Here, we elaborate on these methodological challenges and important considerations in using a standardly tailored design with two arms (one consisting of multidomain interventions tailored to participants' risk profiles and another consisting of active control conditions). We compare this approach to fully factorial designs and highlight the disadvantages and advantages of each. We discuss partial solutions, including analytical strategies such as risk reduction scores that measure reductions in the number or severity of risk factors in each study arm. Positive results can support the causal inference that between-group differences in the primary cognitive outcome were due to risk factor modification. CONCLUSION: Standardly tailored designs are pragmatic and feasible evaluations of multidomain interventions to reduce dementia risk. We propose sensitivity and exploratory analyses of between-group reductions in the severity of risk factors, as a methodology to bolster causal inferences that between-group differences in the primary cognitive outcome are due to the risk factors modified.

Associations of Multidomain Interventions With Improvements in Cognition in Mild Cognitive Impairment: A Systematic Review and Meta-analysis.

Importance: Older adults with mild cognitive impairment (MCI) have the highest risk of progressing to dementia. Evidence suggests that nonpharmacological, single-domain interventions can prevent or delay progressive declines, but it is unclear whether greater cognitive benefits arise from multidomain interventions. Objective: To determine whether multidomain interventions, composed of 2 or more interventions, are associated with greater improvements in cognition among older adults with MCI than a single intervention on its own. Data Sources: MEDLINE, Embase, PsycInfo, AgeLine, CINAHL, and Cochrane Central Register of Controlled Trials were systematically searched from database inception to December 20, 2021. Study Selection: Included studies contained (1) an MCI diagnosis; (2) nonpharmacological, multidomain interventions that were compared with a single active control; (3) older adults aged 65 years and older; and (4) randomized clinical trials. Data Extraction and Synthesis: Data were screened and extracted by 3 independent reviewers. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, random-effects meta-analyses were used to calculate effect sizes from the standardized mean difference (SMD) and 95% CIs. Main Outcomes and Measures: Postintervention cognitive test scores in 7 cognitive domains were compared between single-domain and multidomain groups. Exposure to the intervention was analyzed. Results: A total of 28 studies published between 2011 and 2021, including 2711 older adults with MCI, reported greater effect sizes in the multidomain group for global cognition (SMD, 0.41; 95% CI, 0.23-0.59; P < .001), executive function (SMD, 0.20; 95% CI, 0.04-0.36; P = .01), memory (SMD, 0.29; 95% CI, 0.14-0.45; P < .001), and verbal fluency (SMD, 0.30; 95% CI, 0.12-0.49; P = .001). The Mini-Mental State Examination (SMD, 0.40; 95% CI, 0.17-0.64; P < .001), category verbal fluency test (SMD, 0.34; 95% CI, 0.13-0.56; P = .002), Trail Making Test-B (SMD, 0.46; 95% CI, 0.13-0.80; P = .007), and Wechsler Memory Scale-Logical Memory I (SMD, 0.47; 95% CI, 0.15-0.80; P < .001) and II (SMD, 0.26; 95% CI, 0.07-0.45; P < .001) favored the multidomain group. Exposure to the intervention varied between studies: the mean (SD) duration was 71.3 (36.0) minutes for 19.8 (14.6) weeks with sessions taking place 2.5 (1.1) times per week, and all interventions lasted less than 1 year. Conclusions and Relevance: In this study, short-term multidomain interventions (<1 year) were associated with improvements in global cognition, executive function, memory, and verbal fluency compared with single interventions in older adults with MCI.

Difficulty of falling asleep and non-high-density lipoprotein cholesterol level among Canadian older adults: a cross-sectional analysis of the Canadian Longitudinal Study for Aging baseline data.

OBJECTIVE: To examine whether difficulty of falling asleep (DoFA) is associated with non-high-density lipoprotein cholesterol (non-HDL-C) level among Canadian older adults. METHODS: 26,954 individuals aged 45-85 years from the baseline data of the Canadian Longitudinal Study for Aging were included in this study. DoFA was categorized into five groups by answer to the question "Over the last month, how often did it take you more than 30 min to fall asleep?" Response options are "Never, < 1 time/week, 1-2 times/week, 3-5 times/week, or 6-7 times/week". Non-HDL-C, the difference of total cholesterol and HDL-C, were categorized into five categories based on these cut-offs (< 2.6 mmol/L, 2.6-3.7 mmol/L, 3.7-4.8 mmol/L, 4.8-5.7 mmol/L, and ≥ 5.7 mmol/L). Ordinal logistic regression (logit link) continuation ratio models were used to estimate the odds of higher non-HDL-C levels for DoFA status. Adjusted means of non-HDL-C by DoFA status were estimated by general linear models. All analyses were sex separately using analytic weights to ensure generalizability. RESULTS: The proportions of DoFA in five categories were 41.6%, 25.7%, 13.6%, 9.4%, 9.7% for females and 52.9%, 24.9%, 10.5%, 6.1%, 5.6% for males, respectively. After adjustment of demographical and other covariates (such as depression, comorbidity, sleeping hour, etc.) compared to those who reported never having DoFA, the ORs (95% CIs) of higher levels of non-HDL-C for those whose DoFA status in < 1 time/week, 1-2 times/week, 3-5 times/week, and 6-7 times/week were 1.12 (1.05-1.21), 1.09 (0.99-1.18), 1.20 (1.09-1.33), 1.29 (1.17-1.43) in females and 1.05 (0.98-1.13), 0.95 (0.87-1.05), 1.21 (1.08-1.37), 0.97 (0.85-1.09) in males, respectively. The adjusted means of non-HDL-C among the five DoFA status were 3.68 mmol/L, 3.73 mmol/L, 3.74 mmol/L, 3.82 mmol/L, 3.84 mmol/L for females and 3.54 mmol/L, 3.58 mmol/L, 3.51 mmol/L, 3.69 mmol/L, 3.54 mmol/L for males, respectively. CONCLUSIONS: The results of this study have identified a risk association pattern between DoFA status and non-HDL-C levels in females but not in males. Further research is needed to confirm these findings.

Depression and cardiovascular diseases among Canadian older adults: a cross-sectional analysis of baseline data from the CLSA Comprehensive Cohort.

OBJECTIVE: To examine whether cardiovascular disease (CVD) is associated with depression status. METHODS: 29,328 participants from baseline of Canadian Longitudinal Study for Aging were categorized into four groups of depression status. Group 1: no depression (reference); Group 2: currently with depression symptom (CES-D10 score ≥ 10, negative self-reported depression); Group 3: self-reported depression with no current symptom (CES-D10 score < 10, positive self-reported depression); and Group 4: self-reported depression with current symptom (CES-D10 score ≥ 10, self-reported depression). Six self-reported CVDs were grouped into two related disorders, i.e., heart related disorders (HRD) including heart disease, myocardial infarction, and angina; and peripheral/vascular related disorders (PRD) including hypertension, stroke, and peripheral vascular disease. Adjusted odds ratios (ORs) were used to evaluate the associations between depression and CVDs. RESULTS: 17.3% of participants had self-reported depression, 15.3% were with current depression symptom, 10.5% were with HRD and 34.4% were with PRD. After adjusting for variables of demographics, sex, lifestyles, and comorbidities, compared to reference, people in Group 2 had a slightly increased odds, but most of them were not statistically significant; the ORs (95% CI) were 1.36 (1.18-1.58, P < 0.0001) for HRD and 1.20 (1.09-1.32, P < 0.001) for PRD in Group 3; for people in Group 4, the ORs (95% CI) were 1.31 (1.08-1.61, P < 0.01) for HRD and 1.17 (1.02-1.34, P < 0.05) for PRD. Sex- and age-stratified analyses suggested that the increased ORs were more prevalent in men and people aged < 65 years. CONCLUSIONS: Seniors with self-reported depression are associated with an increased risk of CVDs, the association varies by depression status, sex and age.