P. de Souto Barreto

Vitamin D supplementation in older adults: Searching for specific guidelines in nursing homes

BackgroundThe prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting.DesignCurrent literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition.ResultVitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient’s admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake.ConclusionA population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility.

Cognitive changes with omega-3 polyunsaturated fatty acids in non-demented older adults with low omega-3 index

ObjectivesTo investigate the changes in specific domains of cognitive function in older adults reporting subjective memory complaints with a low omega-3 index receiving omega 3 polyunsaturated fatty acid (n-3 PUFA) supplementation or placebo.DesignThis is a secondary exploratory analysis of the Multidomain Alzheimer Preventive Trial (MAPT) using subjects randomized to the n-3 PUFA supplementation or placebo group.SettingFrench community dwellers aged 70 or over reporting subjective memory complaints, but free from clinical dementia.ParticipantsA subgroup of MAPT subjects in the lowest quartile of omega-3 index distribution with baseline values ≤ 4.83 % (n = 183).InterventionThe n-3 PUFA supplementation group consumed a daily dose of DHA (800 mg) and EPA (a maximum amount of 225 mg) for 3 years. The placebo group received identical capsules comprising liquid paraffin oil.MeasurementsLinear mixed-model repeated-measures analyses were used including baseline, 6, 12, 24 and 36-month follow-up data to assess between-group differences in the change in eight cognitive tests over 36 months.ResultsThere was less decline on the Controlled Oral Word Association Test (COWAT) in the n-3 PUFA supplementation group compared to placebo (p = 0.009; between group mean difference over 36 months, 2.3; 95% CI, 0.6,4.0). No significant differences for any of the other cognitive tests were found, including other tests of executive functioning, although, numerically all results were in favour of the n-3 PUFA supplementation.ConclusionsWe found some evidence that n-3 PUFAs might be beneficial for the maintenance of executive functioning in older adults at risk of dementia with low omega-3 index, but this exploratory finding requires further confirmation. A larger specifically designed randomised controlled trial could be merited.

Cross-sectional associations of total plasma homocysteine with cortical β-amyloid independently and as a function of omega 3 polyunsaturated fatty acid status in older adults at risk of dementia

ObjectivesElevated total plasma homocysteine is a risk factor for Alzheimer’s disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical β-amyloid (Aβ) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored.DesignThis is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial.SettingFrench community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia.ParticipantsIndividuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical Aβ load.MeasurementsCortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models.ResultsWe found that total baseline plasma homocysteine was not significantly associated with cortical Aβ as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E ε4 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical Aβ in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E ε4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66).ConclusionsThe role of n-3 PUFAs on the relationship between homocysteine and cerebral Aβ warrants further investigation.

Association Between Red Blood Cells Omega-3 Polyunsaturated Fatty Acids and White Matter Hyperintensities: The MAPT Study

ObjectivesThe association between circulating biomarkers of red blood cells (RBC) omega-3 polyunsaturated fatty acids (PUFAs) and cerebral white matter hyperintensities (WMH) on the brain MRI remains yet unclear. We investigated the cross-sectional and prospective associations of RBC omega-3 PUFAs with WMH in dementia-free older adults with subjective memory complaints.DesignParticipants were 234 older adults with assessments for both PUFA and MRI near to baseline; among them, 79 also had an MRI assessment at 3-year follow-up. The measurement of WMH volume was obtained by an automated segmentation algorithm. We related individual or combinational baseline RBC omega-3 PUFAs levels with baseline WMH volumes and WMH evolution over 3 years. We carried out multiple (cross-sectional) and mixed-effect (prospective analysis, with random effects at participant’s level) linear regressions with adjustment for age, sex, time interval between date of blood draw for measurement of fatty acids and date of brain MRI, the status of APOE e4 carrier, body mass index, and vascular risk factors. Associations were considered significant at p ≤ 0.006 to take into account multiplicity (8 comparisons).ResultsNone of the eight RBC omega-3 PUFAs tested was significantly associated with WMH at both cross-sectional and prospective analyses.ConclusionsWe did not find any association between omega-3 PUFAs and WMH in non-demented older adults with memory complaints. A longer longitudinal study with data on omega-3 PUFAs and WMH would contribute important information to this field.

Interventions Against Disability in Frail Older Adults: Lessons Learned from Clinical Trials

As the population ages, the number of older people with frailty is expected to increase worldwide with consequent rising of expenditures for healthcare and long-term care. Effective methods for preventing or delaying the onset of disability are urgently required. Frailty is a common and important geriatric condition characterized by age-associated declines in multiple physiological mechanisms, leading to increased vulnerability to stressors and higher risk for adverse health outcomes. Significant advancements have been made in the understanding of the frailty pathophysiological background. Given its multidimensional nature, reversing frailty requires a comprehensive approach. In this context, several studies testing the effects of pharmacological approach, physical activity, nutritional intervention, or cognitive training showed evidence of efficacy in frail older adults. Important innovations in ongoing trials include the development of multidomain interventions. Challenges include the use of trial designs, the development of standardized, sensitive outcome measures, and the need for interventions that can be implemented in resource-poor settings. In this viewpoint paper, based on recent literature, our aim was to identify relevant studies performed to reverse or delay disability in frail older adults.

The Relationship of Omega 3 Polyunsaturated Fatty Acids in Red Blood Cell Membranes with Cognitive Function and Brain Structure: A Review Focussed on Alzheimer’s Disease

Significant research attention has focussed on the identification of nutraceutical agents for the prevention of cognitive decline as a natural means of cognitive preservation in the elderly. There is some evidence for a reduction of brain omega 3 polyunsaturated fatty acids (n-3 PUFAs) in normal aging and in Alzheimer’s disease. n-3 PUFAs exhibit anti-inflammatory and anti-amyloidogenic properties as well as being able to reduce tau phosphorylation. Many observational studies have demonstrated a link between n-3 PUFAs and cognitive aging, and some, but not all, randomized controlled trials have demonstrated a benefit of n-3 PUFA supplementation on cognition, particularly in those subjects with mild cognitive impairment. The identification of a biomarker that reflects n-3 PUFA intake over time and consequent tissue levels is required. In this narrative review we discuss the evidence associating red blood cell membrane n-3 PUFAs with cognitive function and structural brain changes associated with Alzheimer’s disease.

Is Fat Mass Cross-Sectionally Associated with Cortical Aβ Load in the Human Brain?

ObjectivesThe objective of this study was to examine the relationship of fat mass (FM) with brain amyloid (Aβ) load in older adults.MethodsData from the Multidomain Alzheimer’s Preventive Trial (MAPT) for Positron emission tomography and dual-energy X-ray absorptiometry (DXA) were used. Linear regressions controlling for appendicular muscle, age, education, clinical dementia rating scale and Apolipoprotein-E were performed to explore the relationships between FM, trunk FM and Aβ-load.ResultsThirty-nine participants (75.7 ± 4.2 years old) with an average BMI of 27.5 ± 4.0 kg/m2 were analyzed in this study. There were significant and positive associations of both total and trunk FM with Aβ load [0.01 (0.002-0.02) and 0.02 (0.001-0.04), respectively]; however, when adding ApoE-ε4 as a confounder, associations were no longer significant.ConclusionsThis study has found associations between FM as measured by DXA and cerebral Aβ load, suggesting that excessive FM might be involved in AD pathology.

The Effect of Exercise and Social Activity Interventions on Nutritional Status in Older Adults with Dementia Living in Nursing Homes: A Randomised Controlled Trial

ObjectivesExamine the effects of a 24-week exercise intervention against a social intervention on body weight, body mass index (BMI) and nutritional status in PWD living in nursing homes.DesignRandomized controlled trial.ParticipantsNinety-one older people with dementia living in nursing homes. Interventions: Exercise (n=44) or social-based activities (n=47), taking place twice per week, for 60 minutes/session, during 24 weeks.MeasurementsNutritional status was measured with the mini-nutritional assessment (MNA), weight and BMI.ResultsAfter the 24-week intervention, none of MNA (B-coeff. 1.28; 95% CI -2.55 to 0.02), weight (-0.06; -1.58 to 1.45) and BMI (-0.05; -0.85 to 0.74) differed significantly between groups after adjustment for multiplicity. In the social group, MNA significantly improved while it remained stable in the exercise group. The percentage of at-risk and malnourished patients reduced in both groups by more than 6%.ConclusionThe results suggest that social activities have as good effects as exercise activities on nutritional status in PWD nursing home residents.

Shifting from Declines to Improvements: Associations Between a Meaningful Walking Speed Change and Cognitive Evolution Over Three Years in Older Adults

BackgroundAlthough the close relationship between mobility and cognitive declines is well-known, literature has very little questioned whether improvement in walking speed over time could be associated with improvements in cognitive functions. The objective of this study was to examine the associations between a clinically meaningful improvement in walking speed and global and specific cognitive changes in older adults. Design: Prospective cohort study.SettingMultidomain Alzheimer Preventive Trial (MAPT) study.ParticipantsThree-hundred participants from the control group of the MAPT study (mean age 74.8 ± 4.2; 57% women).MeasurementsThe 4-m usual walking speed, global cognition, memory, executive functions, and processing speed measures were collected at baseline, and at 6, 12, 24 and 36 months. Participants were categorized into three groups according to their walking speed change over the three-year study: 1/ Non-Improvers (participants not presenting an increase ≥0.05m/sec on walking speed; n=138); 2/ Improvers (increase ≥0.05m/sec; n=40); Cyclic (≥0.05m/sec improvement at some time points without maintaining it through the whole period; n=122).ResultsAdjusted mixed-effect linear regressions revealed that walking speed improvers did not significantly differ from participants who never or temporarily improved their walking speed on all of global and specific cognitive functions over three years. Nevertheless, a sensitivity analysis (excluding participants with a nonclinical walking speed improvement) indicated specific cognitive trajectories per group associated with better episodic memory scores for Improvers compared to non-improvers (β=2.41, 95% CI=.12 - 4.71; p=.039).ConclusionThis study found that the overtime trajectories of cognitive functions did not differ as a function of clinically meaningful walking speed changes in older adults. Nevertheless, secondary analyses provided new insights on the relationship between walking speed and specific cognitive functions. The novelty of this approach (switching from declines to improvements) should be considered in future large-scale, observational longitudinal studies.

Association of cortical β-amyloid with erythrocyte membrane monounsaturated and saturated fatty acids in older adults at risk of dementia

ObjectivesWe examined the relationships between erythrocyte membrane monounsaturated fatty acids (MUFAs) and saturated fatty acids (SFAs) and cortical β-amyloid (Aβ) load in older adults reporting subjective memory complaints.DesignThis is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial.SettingFrench community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia.ParticipantsParticipants of this study were 61 individuals from the placebo arm of the MAPT trial with data on erythrocyte membrane fatty acid levels and cortical Aβ load.MeasurementsCortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Fatty acids were measured in erythrocyte cell membranes using gas chromatography. Associations between erythrocyte membrane MUFAs and SFAs and cortical Aβ load were explored using adjusted multiple linear regression models and were considered significant at p ≤ 0.005 (10 comparisons) after correction for multiple testing.ResultsWe found no significant associations between fatty acids and cortical Aβ load using multiple linear regression adjusted for age, sex, education, cognition, PET-scan to clinical assessment interval, PET-scan to blood collection interval and apolipoprotein E (ApoE) status. The association closest to significance was that between erythrocyte membrane stearic acid and Aβ (B-coefficient 0.03, 95 % CI: 0.00,0.05, p = 0.05). This association, although statistically non-significant, appeared to be stronger amongst ApoE ε4 carriers (B-coefficient 0.04, 95 % CI: -0.01,0.09, p = 0.08) compared to ApoE ε4 non-carriers (B-coefficient 0.02, 95 % CI: -0.01,0.05, p = 0.18) in age and sex stratified analysis.ConclusionFuture research in the form of large longitudinal observational study is needed to validate our findings, particularly regarding the potential association of stearic acid with cortical Aβ.