Cannabidiol as a Treatment for Neurobiological, Behavioral, and Psychological Symptoms in Early-Stage Dementia: A Double-Blind, Placebo-Controlled Clinical Trial Protocol.

Rationale: The slowing of disease progression in dementia in the early stages of diagnosis is paramount to improving the quality of life for those diagnosed and their support networks. Accumulating evidence suggests that CBD, a constituent of Cannabis sativa, is associated with neuroprotective, neuroendocrine, and psychotherapeutic effects, suggesting that it may be beneficial to dementia treatment. However, no published human study to date has examined this possibility. This trial aims to determine whether daily treatment with CBD over a 12-week period is associated with improved neurobiological, behavioral, and psychological outcomes in individuals living with early-stage dementia. Methods: Sixty participants with early-stage dementia will be recruited for a randomized, double-blind, placebo-controlled clinical trial. Participants will be randomized into either 99.9% pure CBD or placebo treatment conditions and administered two capsules per day for 12 weeks. Participants will commence a 200 mg/day dose for 2 weeks before escalating to 300 mg/day for the remaining 10 weeks. Neuroimaging and blood-based neuroendocrine profiles will be assessed at baseline and post-treatment. Psychological and behavioral symptoms will be assessed at baseline, 6 weeks, and post-treatment. Monitoring of health and side-effects will be conducted through weekly home visits. Discussion: This study is among the first to investigate the effects of isolated CBD in improving neuroanatomical and neuroendocrine changes, alongside psychological symptoms, during the early stages of dementia diagnosis. The outcomes of this trial have the capacity to inform a potential novel and accessible treatment approach for individuals living with early-stage dementia, and in turn, improve quality of life, prognoses, and treatment outcomes. Trial Registration: This trial has been registered with the Therapeutic Goods Administration (CT-2020-CTN-03849-1v2) and the Australian and New Zealand Clinical Trials Registry (ACTRN12621001364864).

Feasibility of home-based dietetic intervention to improve the nutritional status of older adults post-hospital discharge.

AIM: To determine if a model of home-based dietetic care improves dietary intake and weight status in a specific group of older adults post-hospitalisation. METHODS: The Department of Veterans' Affairs clients aged 65 years and over were recruited from hospitals in a regional area of New South Wales, Australia (n = 32 men, n = 36 women). Nutritional status was assessed at home at baseline (within two weeks post-discharge) and three months post-discharge using a diet history, a food frequency checklist and Mini Nutritional Assessment (MNA). Personalised dietary advice was provided by a single dietitian according to participants' nutritional status. RESULTS: Mean body weight improved significantly (P = 0.048), as well as mean MNA score (21.9 ± 3.5 vs 25.2 ± 3.1) (P < 0.001). Mean energy, protein and micronutrient intakes were adequate at baseline and three months, except for vitamin D. At three months, the underweight group (body mass index (BMI) < 23 kg/m2 ) had significantly higher mean protein intake per body weight (1.7 ± 0.4 g/kg) compared to those who were a desirable weight (BMI 23-27 kg/m2 ) (1.4 ± 0.3 g/kg) or overweight (BMI>27 kg/m2 ) (1.1 ± 0.3 g/kg) peers (P < 0.001). There was significant improvement in energy intake contributed from oral nutrition supplements (+95.5 ± 388.2 kJ/day) and milk (+259.6 ± 659.8 kJ/day). CONCLUSIONS: Dietetic intervention improved nutritional status 3 months after hospital discharge in older adults living in the community.

Should oral nutritional supplementation be given to undernourished older people upon hospital discharge? A controlled trial.

OBJECTIVES: To determine whether the oral nutritional supplementation of undernourished older people upon discharge from hospital improves muscle function and reduces disability. DESIGN: Randomized controlled trial. SETTING: Community-based study in two centers in Scotland. PARTICIPANTS: Two hundred fifty-three people. INTERVENTION: Randomization to oral nutritional supplementation (600 kcal/d) or control supplement of 200 kcal/d. MEASUREMENTS: Primary outcome (20-point activity of daily living Barthel Index) and secondary outcomes (handgrip strength, Sit-to-Stand test, and Euroquol) were measured at baseline (after discharge from the hospital and before supplement was commenced) and 8 and 16 weeks and accelerometry-measured physical activity levels at baseline and 16 weeks. Falls were recorded prospectively. RESULTS: Mean age was 82. There was no significant difference in change in Barthel score between supplement and control groups (adjusted mean difference=0.28, 95% confidence interval (CI)=-0.28-0.84). Handgrip strength improved more in the supplemented group (adjusted mean difference=1.52 kg, 95% CI=0.50-2.55; P=.004). The supplemented group exhibited modestly greater vector movement (overall activity) than controls (P=.02). There were no significant between-group differences in Sit-to-Stand test, health-related quality of life, or falls. Adherence was 38.2% in the nutritional supplement group and 50.0% in the control supplement group. Weight did not increase in the nutritional supplement group as a whole, but on-treatment analysis adjusting for adherence showed a mean weight gain of 1.17 kg (95% CI=0.07-2.27; P=.04) more than in controls. CONCLUSION: Oral nutritional supplementation of undernourished older people upon hospital discharge did not reduce disability, despite improving handgrip strength and modestly increasing objectively measured physical activity levels. Lack of an effect of the nutritional supplement used in this study may have been due to low adherence, suggesting that different approaches to nutritional supplementation need to be tested in this population.

Protein and energy supplementation in elderly people at risk from malnutrition.

BACKGROUND: Evidence for the effectiveness of nutritional supplements containing protein and energy, often prescribed for older people, is limited. Malnutrition is more common in this age group and deterioration of nutritional status can occur during illness. It is important to establish whether supplementing the diet is an effective way of improving outcomes for older people at risk from malnutrition. OBJECTIVES: This review examined trials for improvement in nutritional status and clinical outcomes when extra protein and energy were provided, usually as commercial 'sip-feeds'. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, Healthstar, CINAHL, BIOSIS, CAB abstracts. We also hand searched nutrition journals and reference lists and contacted 'sip-feed' manufacturers. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of oral protein and energy supplementation in older people, with the exception of groups recovering from cancer treatment or in critical care. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials prior to inclusion and independently extracted data and assessed trial quality. Authors of trials were contacted for further information as necessary. MAIN RESULTS: Sixty-two trials with 10,187 randomised participants have been included in the review. Maximum duration of intervention was 18 months. Most included trials had poor study quality. The pooled weighted mean difference (WMD) for percentage weight change showed a benefit of supplementation of 2.2% (95% confidence interval (CI) 1.8 to 2.5) from 42 trials. There was no significant reduction in mortality in the supplemented compared with control groups (relative risk (RR) 0.92, CI 0.81 to 1.04) from 42 trials. Mortality results were statistically significant when limited to trials in which participants (N = 2461) were defined as undernourished (RR 0.79, 95% CI 0.64 to 0.97).The risk of complications was reduced in 24 trials (RR 0.86, 95% CI 0.75 to 0.99). Few trials were able to suggest any functional benefit from supplementation. The WMD for length of stay from 12 trials also showed no statistically significant effect (-0.8 days, 95% CI -2.8 to 1.3). Adverse effects included nausea or diarrhoea. AUTHORS' CONCLUSIONS: Supplementation produces a small but consistent weight gain in older people. Mortality may be reduced in older people who are undernourished. There may also be a beneficial effect on complications which needs to be confirmed. However, this updated review found no evidence of improvement in functional benefit or reduction in length of hospital stay with supplements. Additional data from large-scale multi-centre trials are still required.

Does vitamin D stop inpatients falling? A randomised controlled trial.

BACKGROUND: Vitamin D deficiency is common in older people and may increase risk of falls and fracture. Hospital inpatients are at particular risk of falling. Previous studies suggest that vitamin D improves neuromuscular function and reduces falls. OBJECTIVE: To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are inpatients. DESIGN: Randomised, double-blind, controlled study. PARTICIPANTS: two hundred and five acute admissions >65 years to a geriatric medical unit. METHODS: Patients were randomised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg, until discharge or death. RESULTS: Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days (IQR 14.75-71.00). In a pre-selected sub-group (54/205 participants), median admission vitamin D level = 22.00 nmol/l (IQR 15.00-30.50). This did not significantly increase in the treatment versus control group. Median study drug adherence = 88%, with no significant difference between study groups (Mann-Whitney: P = 0.711). Although there were fewer fallers in the vitamin D cohort, this did not reach statistical significance (vitamin D: calcium = 36:45 fallers; RR 0.82 (CI 0.59-1.16). Neither the mean number of falls (vitamin D: calcium = 1.040:1.155; Mann-Whitney P = 0.435) or time to first fall (Log-rank test P = 0.377) differed between groups. CONCLUSIONS: In a population of geriatric hospital inpatients, vitamin D did not reduce the number of fallers. Routine supplementation cannot be recommended to reduce falls in this group.

Meta-analysis: protein and energy supplementation in older people.

BACKGROUND: Protein and energy undernutrition is common in older people, and further deterioration may occur during illness. PURPOSE: To assess whether oral protein and energy supplementation improves clinical and nutritional outcomes for older people in the hospital, in an institution, or in the community. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HealthStar, CINAHL, BIOSIS, and CAB abstracts. The authors included English- and non-English-language studies and hand-searched journals, contacted manufacturers, and sought information from trialists. The date of the most recent search of CENTRAL and MEDLINE is June 2005. STUDY SELECTION: Randomized and quasi-randomized controlled trials of oral protein and energy supplementation compared with placebo or control treatment in older people. DATA EXTRACTION: Two reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. DATA SYNTHESIS: Fifty-five trials were included (n = 9187 randomly assigned participants). For patients in short-term care hospitals who were given oral supplements, evidence suggested fewer complications (Peto odds ratio, 0.72 [95% CI, 0.53 to 0.97]) and reduced mortality (Peto odds ratio, 0.66 [CI, 0.49 to 0.90]) for those undernourished at baseline. Few studies reported evidence that suggested any change in mortality, morbidity, or function for those given supplements at home. Ten trials reported gastrointestinal disturbances, such as nausea, vomiting, and diarrhea, with oral supplements. LIMITATIONS: The quality of most studies, as reported, was poor, particularly for concealment of allocation and blinding of outcome assessors. Many studies were too small or the follow-up time was too short to detect a statistically significant change in clinical outcome. The clinical results are dominated by 1 very large recent trial in patients with stroke. Although this was a high-quality trial, few participants were undernourished at baseline. CONCLUSIONS: Oral nutritional supplements can improve nutritional status and seem to reduce mortality and complications for undernourished elderly patients in the hospital. Current evidence does not support routine supplementation for older people at home or for well-nourished older patients in any setting.

Can prescription of sip-feed supplements increase energy intake in hospitalised older people with medical problems?

A blinded randomised controlled trial of prescribed oral sip-feed supplements compared with routine hospital practice was undertaken in acute admissions to a geriatric medicine department. Patients were eligible for inclusion if they were admitted from home, were not obese (BMI>75th percentile), had no swallowing difficulties and were not deemed to be in the terminal stage of illness. On admission they were stratified by nutritional status (BMI<5th, >5th to <25th, >25th to <75th percentile) and randomised. The intervention group received 120 ml oral sip-feed supplement prescribed three times per d in the medicine prescription chart (22.5 g protein, 2260 kJ (540 kcal) energy/d) distributed at medication rounds for the duration of hospital stay. The control group received routine hospital care. Outcomes were patient compliance with supplement, total energy intake and nursing staff views of the method. Patients were randomised to receive supplements (n 186 of total n 381). Half had full compliance and three-quarters at least moderate compliance. Total energy intake was significantly increased, on average, in the intervention group (P=0.001). The proportion of patients meeting estimated minimum energy requirements was significantly increased (P=0.023), but was still <50 % for the sample of patients in the intervention group. The present study suggests this method is acceptable to patients and staff and improves total energy intake. However, the amount prescribed did not ensure minimum energy requirements were met in all cases.