Effects of virtual reality guided meditation in older adults: the protocol of a pilot randomized controlled trial.

Background: Virtual reality (VR) based meditation has been shown to help increase relaxation and decrease anxiety and depression in younger adults. However, this has not been studied in Randomized Controlled Trials (RCT) in the older adult population. The aim of this RCT is to assess the feasibility and acceptability of a VR-guided meditation intervention for community-dwelling older adults and its effect on stress and mental health. Methods: We will recruit 30 participants aged ≥ 60 years, whose perceived stress score (PSS) is > 14 (moderate stress), and randomize them 1:1 to the intervention or control waitlist group. The intervention will involve exposure to eight 15-min VR-guided meditation sessions distributed twice weekly for 4-weeks. Two modalities will be offered: in-home and at the hospital. Data analysis: Baseline and post-intervention assessments will evaluate perceived stress, anxiety, depression, sleep quality, quality of life, and mindfulness skills. Analyses will employ mixed methods repeated ANOVA tests. Qualitative analyses through semi-structured interviews and participant observation will be used to assess participants' experiences. Study outcomes include: (A) feasibility and acceptability compared to a waitlist control (B) stress, using the Perceived Stress Scale (PSS); (C) anxiety, and depression, using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9); (D) insomnia, quality of life and mindfulness skills, using the Athens Insomnia Scale (AIS), Quality of Life Questionnaire (EQ-5D-5L) and Five Facets Mindfulness Questionnaire Short Forms (FFMQ-SF), respectively. We will also measure immersive tendencies, sickness and sense of presence using the Simulator Sickness Questionnaire (SSQ) and the Presence Questionnaire (PQ). Discussion: Virtual reality-guided meditation could be an acceptable, feasible, safe, and cost-effective novel alternative health intervention for improving older adults' mental health.Clinical trial registration: NCT05315609 at https://clinicaltrials.gov.

Therapeutic efficacy of the Ginkgo special extract EGb761® within the framework of the mitochondrial cascade hypothesis of Alzheimer's disease.

OBJECTIVES: The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction as an important common pathomechanism for the whole spectrum of age-associated memory disorders from cognitive symptoms in the elderly over mild cognitive impairment to Alzheimer's dementia. Thus, a drug such as the Ginkgo special extract EGb 761® which improves mitochondrial function should be able to ameliorate cognitive deficits over the whole aging spectrum. METHODS: We review the most relevant publications about effects of EGb 761® on cognition and synaptic deficits in preclinical studies as well as on cognitive deficits in man from aging to dementia. RESULTS: EGb 761® improves mitochondrial dysfunction and cognitive impairment over the whole spectrum of age-associated cognitive disorders in relevant animal models and in vitro experiments, and also shows clinical efficacy in improving cognition over the whole range from aging to Alzheimer's or even vascular dementia. CONCLUSIONS: EGb 761® shows clinical efficacy in the treatment of cognitive deficits over the whole spectrum of age-associated memory disorders. Thus, EGb 761® can serve as an important pharmacological argument for the mitochondrial cascade hypothesis of dementia.

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). METHODS: To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. RESULTS: Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. CONCLUSIONS: Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms.

Imaging in vivo glutamate fluctuations with [(11)C]ABP688: a GLT-1 challenge with ceftriaxone.

Molecular imaging offers unprecedented opportunities for investigating dynamic changes underlying neuropsychiatric conditions. Here, we evaluated whether [(11)C]ABP688, a positron emission tomography (PET) ligand that binds to the allosteric site of the metabotropic glutamate receptor type 5 (mGluR5), is sensitive to glutamate fluctuations after a pharmacological challenge. For this, we used ceftriaxone (CEF) administration in rats, an activator of the GLT-1 transporter (EAAT2), which is known to decrease extracellular levels of glutamate. MicroPET [(11)C]ABP688 dynamic acquisitions were conducted in rats after a venous injection of either saline (baseline) or CEF 200 mg/kg (challenge). Binding potentials (BP(ND)) were obtained using the simplified reference tissue method. Between-condition statistical parametric maps indicating brain regions showing the highest CEF effects guided placement of microdialysis probes for subsequent assessment of extracellular levels of glutamate. The CEF administration increased [(11)C]ABP688 BP(ND) in the thalamic ventral anterior (VA) nucleus bilaterally. Subsequent microdialysis assessment revealed declines in extracellular glutamate concentrations in the VA. The present results support the concept that availability of mGluR5 allosteric binding sites is sensitive to extracellular concentrations of glutamate. This interesting property of mGluR5 allosteric binding sites has potential applications for assessing the role of glutamate in the pathogenesis of neuropsychiatric conditions.

Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials.

The objective of this systematic review was to evaluate current evidence for the efficacy of Ginkgo biloba extract EGb 761(®) in dementia. Seven of 15 randomized, placebo-controlled trials in patients with dementia identified by database searches met all our selection criteria and were included in the meta-analysis. In these trials, patients were treated with 120 mg or 240 mg per day of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment. Tolerability was evaluated by risk differences based on incidences of adverse events and premature discontinuation rates. Of 2,684 outpatients randomized to receive treatment for 22-26 weeks, 2,625 represented the full analysis sets (1,396 for EGb 761 and 1,229 for placebo). Standardized mean differences for change in cognition (-0.52; 95% confidence interval [CI] -0.98, -0.05; P=0.03), activities of daily living (-0.44; 95% CI -0.68, -0.19; P<0.001), and global rating (-0.52; 95% CI -0.92, -0.12; P=0.01) significantly favored EGb 761 compared with placebo. Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. Treatment-associated risks in terms of relative risks of adverse events and premature withdrawal rates did not differ noticeably between the two treatment groups. In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia.

Alzheimer's disease dietary supplements in websites.

Consumer demand for health information and health services has rapidly evolved to capture and even propel the movement to online health information seeking. Seventeen percent (52 million) of health information internet users will look for information about memory loss, dementia and Alzheimer's disease (AD) (Fox Pew Internet & American life project: Online health search. Report. Pew Research Center. http://pewinternet.org/Reports/2006/Online-Health-Search-2006.aspx 2006, Pew Research Center. http://pewinternet.org/Reports/2011/HealthTopics.aspx 2011). We examined the content of the 25 most frequently retrieved websites marketing AD dietary supplements. We found that the majority of websites and their products claimed AD-related benefits, including improvement and enhancement of function, treatment for AD, prevention of AD, maintenance of function, delayed progression of AD, and decreased symptoms. Supplements were described as effective, natural, powerful or strong, dependable and pure or of high quality. Peer reviewed references to proper scientific studies were infrequent on websites. Statements highlighting the risks of dietary supplements were as common as statements mitigating or minimizing these risks. Different strategies were used to promote supplements such as popular appeals and testimonials. Further enforcement of relevant policy is needed and preparation of clinicians to deal with requests of patients and caregivers is indicated.

Memantine effects measured with the Relevant Outcome Scale for Alzheimer's disease in an open-label, single-arm, multicenter clinical study.

OBJECTIVE: The Relevant Outcome Scale for Alzheimer's disease (ROSA) is a novel, valid, and reliable instrument for multidimensional assessment of Alzheimer's disease (AD) symptoms across all severity stages. The ROSA and four standard instruments -- the Alzheimer's disease Assessment Scale-cognitive (ADAS-cog), Severe Impairment Battery (SIB), Disability Assessment for Dementia (DAD), and the Neuropsychiatric Inventory (NPI) -- were used in an open-label, multicenter, single-arm clinical study to assess treatment-induced changes in cognitive, functional, and behavioral symptoms in patients with AD at different severity stages. METHODS: A total of 451 patients were treated with memantine (initiated at 5 mg/day and up-titrated with 5 mg weekly to a final dose of 20 mg/day) for 12 weeks. The study endpoints comprised changes from baseline in the scores of the ROSA, ADAS-cog, SIB, DAD, and NPI as well as global changes on the Clinical Global Impression of Change (CGI-C). Analyses were performed for the overall population and by AD severity stage (early, middle, late). RESULTS: The ROSA scores increased significantly after a 12-week treatment in all study groups except for early stage. Mean changes in the ADAS-cog score indicated a trend towards worsening in early and middle stages. Non-significant changes were shown by the SIB, NPI, and DAD assessments at week 12. The CGI-C demonstrated 'minimal improvement' or 'no change' for most of the patients. Overall, memantine treatment was safe and well tolerated. CONCLUSION: The results demonstrated the ROSA feasibility in daily practice for assessment of memantine effects over time in patients with moderate and late AD.

Management of agitation and aggression associated with Alzheimer disease.

Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment (over 6-12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics-preliminary evidence for memantine, carbamazepine, and citalopram is encouraging.

Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: evidence from a cognitive intervention program.

The efficacy of cognitive training was assessed in persons with mild cognitive impairment (MCI) and persons with normal cognitive aging. Forty-seven participants were included in this study: 28 with MCI and 17 controls. Twenty-one participants received intervention (20 MCI and 9 controls) and 16 participants (8 MCI and 8 controls) received no intervention (waiting-list group). The intervention focused on teaching episodic memory strategies. Three tasks of episodic memory (list recall, face-name association, text memory) were used as primary outcome measures. Results were analyzed using analyses of variance. The intervention effect (pre- and post-intervention difference) was significant on two of the primary outcome measures (delayed list recall and face-name association). A significant pre-post-effect was also found on measures of subjective memory and well-being. There was no improvement in the performance of groups of individuals with MCI and normal elderly persons who did not receive the intervention. These results suggest that persons with MCI can improve their performance on episodic memory when provided with cognitive training.