Vitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to... Show moreVitamin D is a hormone produced in the skin via a non-enzymatic process involving ultraviolet light.It is well known that the physiology of aging makes older people particularly susceptible to vitamin D deficiency and that, if untreated, it can have serious health consequences. This thesis deliberates on the topics of vitamin D supplementation in older people in light of the current guidelines and on the possible additional effects of ultraviolet light beyond vitamin D synthesis on nursing home residents. We present a cross-sectional study in nursing home residents aged 70 years and over designed to evaluate the efficacy of vitamin D supplementation in achieving vitamin D sufficiency. We also discuss the different supplementation strategies for nursing home residents and community dwelling persons aged 70 years and over based on a survey administered to general practitioners and elderly care physicians in the Netherlands.In the second part we concentrate on additional effects of ultraviolet light beyond vitamin D synthesis. We describe our systematic review of literature on the effect of ultraviolet light, when applied to the skin or eyes, on mood, depression and well-being. We present also our randomized controlled trial on the effect of ultraviolet radiation compared with oral vitamin D supplementation on the well-being of nursing home residents with dementia. Further we use the data of the RCT to carry out a post-hoc analysis to compare the effect of vitamin D alone compared with ultraviolet radiation on the blood pressure of old people with dementia. Show less
Introduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially... Show moreIntroduction: Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. Method: We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. Results: Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. Conclusion: There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia. Show less
Background Observational studies have reported an inverse association between ultraviolet (UV) radiation and hypertension. The aim of this study was to assess differences in blood pressure changes... Show moreBackground Observational studies have reported an inverse association between ultraviolet (UV) radiation and hypertension. The aim of this study was to assess differences in blood pressure changes between persons with dementia receiving UV light versus vitamin D (VD) supplementation. Methods Post-hoc analysis of randomized controlled trial data concerning nursing home residents with dementia (N = 61; 41 women, mean age 84.8 years). The participants received half-body UV irradiation, twice weekly over 6 months, at one standard erythema dose (UV group, n = 22) or 5600 international units of cholecalciferol once a week (VD group, n = 39). Short-term effects were evaluated after 1 month and long-term effects after 3 and 6 months. Differences in blood pressure changes were assessed using linear mixed models. Results With the VD group as a reference, the estimated difference in mean change of systolic blood pressure was - 26.0 mmHg [95% confidence interval (CI) -39.9, - 12.1, p = .000] at 1 month, 4.5 mmHg (95% CI -6.8, 15.9, p = 0.432) at 3 months, and 0.1 (95% CI -14.1, 14.3, p = 0.83) at 6 months. The estimated difference in diastolic blood pressure was - 10.0 mmHg (95% CI -19.2, - 0.7, p = 0.035) at 1 month, 3.6 mmHg (95% CI -4.1, 11.2, p = 0.358) at 3 months, and 2.7 (95% CI -6.8, 12.1, p = 0.580) at 6 months. Conclusions UV light had only a short-term effect but not a long-term effect on blood pressure reduction compared to VD use in this sample of normotensive to mild hypertensive nursing home residents with dementia. Future studies will be needed to determine the effect of UV light in different samples of the population and especially in a population with hypertension. Show less
Klapwijk, M.S.; Bolt, S.R.; Boogaard, J.A.N.; Koppel, M. ten; Gijsberts, M.J.H.E.; Leussen, C. van; ... ; Steen, J. van der 2021
Background: Dementia palliative care is increasingly subject of research and practice improvement initiatives. Aim: To assess any changes over time in the evaluation of quality of care and quality... Show moreBackground: Dementia palliative care is increasingly subject of research and practice improvement initiatives. Aim: To assess any changes over time in the evaluation of quality of care and quality of dying with dementia by family caregivers. Design: Combined analysis of eight studies with bereaved family caregivers' evaluations 2005-2019. Setting/participants: Family caregivers of nursing home residents with dementia in the Netherlands (n = 1189) completed the End-of-Life in Dementia Satisfaction With Care (EOLD-SWC; quality of care) and Comfort Assessment in Dying (EOLD-CAD, four subscales; quality of dying) instruments. Changes in scores over time were analysed using mixed models with random effects for season and facility and adjustment for demographics, prospective design and urbanised region. Results: The mean total EOLD-SWC score was 33.40 (SD 5.08) and increased by 0.148 points per year (95% CI, 0.052-0.244; adjusted 0.170 points 95% CI, 0.055-0.258). The mean total EOLD-CAD score was 30.80 (SD 5.76) and, unadjusted, there was a trend of decreasing quality of dying over time of -0.175 points (95% CI, -0.291 to -0.058) per year increment. With adjustment, the trend was not significant (-0.070 EOLD-CAD total score points, 95% CI, -0.205 to 0.065) and only the EOLD-CAD subscale 'Well being' decreased. Conclusion: We identified divergent trends over 14 years of increased quality of care, while quality of dying did not increase and well-being in dying decreased. Further research is needed on what well-being in dying means to family. Quality improvement requires continued efforts to treat symptoms in dying with dementia. Show less
Topic: Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. Findings on the hypothesized bidirectional... Show moreTopic: Visual impairment (VI) and cognitive impairment (CIM) are prevalent age-related conditions that impose substantial burden on the society. Findings on the hypothesized bidirectional association of VI and CIM remains equivocal. Hence, we conducted a systematic review and meta-analysis to examine this bidirectional relationship.Methods: PubMed, Embase, and Cochrane Central registers were searched systematically for observational studies, published from inception until April 6, 2020, in adults 40 years of age or older reporting objectively measured VI and CIM assessment using clinically validated cognitive screening tests or diagnostic evaluation. Meta-analyses on cross-sectional and longitudinal associations between VI and CIM outcomes (any CIM assessed using screening tests and clinically diagnosed dementia) were examined. Random effect models were used to generate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We also examined study quality, publication bias, and heterogeneity.Results: Forty studies were included (n=47 913 570). Meta-analyses confirmed that persons with VI were more likely to have CIM, with significantly higher odds of: (1) any CIM (cross-sectional: OR, 2.38 [95% CI, 1.84-3.07]; longitudinal: OR, 1.66 [95% CI, 1.46-1.89]) and (2) clinically diagnosed dementia (cross-sectional: OR, 2.43 [95% CI, 1.48-4.01]; longitudinal: OR, 2.09 [95% CI, 1.37-3.21]) compared with persons without VI. Significant heterogeneity was explained partially by differences in age, sex, and follow-up duration. Also, some evidence suggested that individuals with CIM, relative to cognitively intact persons, were more likely to have VI, with most articles (8/9 [89%]) reporting significantly positive associations; however, meta-analyses on this association could not be conducted because of insufficient data.Discussion: Overall, our work suggests that VI is a risk factor of CIM, although further work is needed to confirm the association of CIM as a risk factor for VI. Strategies for early detection and management of both conditions in older peoplemay minimize individual clinical and public health consequences. (C) 2020 by the American Academy of Ophthalmology Show less
As the number of patients suffering from dementia is still growing, most of the patients display behavioral symptoms at some time during the disease and these behavioral symptoms lower the quality... Show moreAs the number of patients suffering from dementia is still growing, most of the patients display behavioral symptoms at some time during the disease and these behavioral symptoms lower the quality of life and increase the burden of caregivers, adequate management of these symptoms is warranted. However, the etiology and management of behavioral symptoms is complex, resulting in (mis)use of pharmacological interventions: a cure which is often worse than the disease. In healthy adults, caffeine is known to influence behavior. Four different studies were conducted to see if caffeine is an easy to adjust cause or a pragmatic intervention for behavioral symptoms in patients with dementia. Based on these studies, we conclude caffeine can influence behavior in persons with dementia, but most likely not in all persons, not in all situations and not all of the time; but it can have an influence. In clinical practice it is advisable to consider caffeine as a possible moderator in the clinical assessment of behavioral symptoms in persons with dementia. Show less
Background: The cholinergic system and M-1 receptor remain an important target for symptomatic treatment of cognitive dysfunction. The selective M-1 receptor partial agonist HTL0018318 is under... Show moreBackground: The cholinergic system and M-1 receptor remain an important target for symptomatic treatment of cognitive dysfunction. The selective M-1 receptor partial agonist HTL0018318 is under development for the symptomatic treatment of Dementia's including Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). We investigated the safety, tolerability, pharmacokinetics and exploratory pharmacodynamics of multiple doses of HTL0018318 in healthy younger adults and elderly subjects.Methods: This randomised, double blind, placebo-controlled study was performed, investigating oral doses of 15-35 mg/day HTL0018318 or placebo in 7 cohorts of healthy younger adult (n = 36; 3 cohorts) and elderly (n = 50; 4 cohorts) subjects. Safety, tolerability and pharmacokinetic measurements were performed. Pharmacodynamics were assessed using a battery of neurocognitive tasks and electrophysiological biomarkers of synaptic and cognitive functions.Results: HTL0018318 was generally well-tolerated in multiple doses up to 35 mg/day and were associated with mild or moderate cholinergic adverse events. There were modest increases in blood pressure and pulse rate when compared to placebo-treated subjects, with tendency for the blood pressure increase to attenuate with repeated dosing. There were no clinically significant observations or changes in blood and urine laboratory measures of safety or abnormalities in the ECGs and 24-h Holter assessments. HTL0018318 plasma exposure was dose-proportional over the range 15-35 mg. Maximum plasma concentrations were achieved after 1-2 h. The apparent terminal half-life of HTL0018318 was 16.1 h (+/- 4.61) in younger adult subjects and 14.3 h (+/- 2.78) in elderly subjects at steady state. HTL0018318 over the 10 days of treatment had significant effects on tests of short-term (working) memory (n-back) and learning (Milner maze) with moderate to large effect sizes.Conclusion: Multiple doses of HTL0018138 showed well-characterised pharmacokinetics and were safe and generally well-tolerated in the dose range studied. Pro-cognitive effects on short-term memory and learning were demonstrated across the dose range. These data provide encouraging data in support of the development of HTL0018138 for cognitive dysfunction in AD and DLB. Show less
