Emotion regulation in older nursing home residents with and without depression and younger comparison samples.

OBJECTIVES: We aimed to increase the understanding of emotion regulation (ER) and depression in older residents. METHODS: A sample of depressed and non-depressed nursing home residents (N = 164, Mage = 82.63) were compared to younger patients with depression (N = 163, Mage = 37.4) and a non-clinical student sample (N = 635, Mage = 23.82). The Affective Style Questionnaire (ASQ), and in the older adults, cognitive capacity, access to people, and a facet of mindfulness were assessed. With two MANCOVAs ER was compared between the depressed and non-depressed participants. RESULTS: Depressed and non-depressed individuals differed significantly regrading Adjusting and Tolerating after controlling for age, with an interaction significant for Tolerating (p = .034). Access to people and monitoring of experience were significant predictors of ER in residents. CONCLUSIONS: Interventions that include ER for older patients in nursing homes as a possibility to reduce age related stereotypes are discussed.

[Non-pharmacological Therapies of Dementia - an Update]. / Nicht pharmakologische Therapien bei Demenz.

Non-pharmacological Therapies of Dementia - an Update Abstract: Non-pharmacological interventions for people with dementia are intended to improve quality of life and well-being, alleviate psychopathological and behavioral symptoms, and also offer caregivers support and opportunities to promote resilience. Against the background of the multiple failures in the field of pharmacological-therapeutic research, these approaches have become increasingly important. This is an up-to-date overview of the most important non-drug interventions for people with dementia and related recommendations for therapeutic use according to the current state of research and the recommendations of AWMF S3 guideline "dementia". The most important interventions from this therapeutic spectrum are cognitive stimulation to maintain cognitive functioning, physical activation, and creative therapeutic offers to promote communication skills and social participation. In the meantime, access to these diverse psychosocial interventions has also been supplemented by digital technology. What these interventions have in common is that they are based on the individual cognitive and physical resources of those affected, improve quality of life and mood, and promote participation and self-efficacy. In addition to psychosocial interventions, nutrition-related approaches ("medical food") and non-invasive neurostimulation have recently also shown potential in the context of non-drug therapy for people with dementia.

General practitioners' communication on complementary and integrative medicine for cancer patients: Findings from an analysis of consultations with standardised patients.

OBJECTIVE: Our aim was to explore whether general practitioners (GPs) communicate with cancer patients on complementary and integrative medicine (CIM) in a patient-centred and case-specific manner. METHODS: We designed two cases of standardised breast cancer patients and allocated 29 GPs to hold a consultation either with Case 1 or Case 2. Case 1 presented with fears of possible physical side effects of hormone treatment. Case 2 feared a loss in social functioning because of nausea and emesis as possible side effects of chemotherapy. Consultations were audiotaped and analysed using the Roter Interaction Analysis System (RIAS). We analysed whether recommended CIM treatments and GPs' focus on psychosocial or medical and therapy-related content differed according to whether they were counselling Case 1 or Case 2. RESULTS: In consultations with Case 1, GPs rather focused on medical and therapy-related content and most often recommended mistletoe, diets and sports. In contrast, GPs focused on psychosocial content and they most often recommended methods of self-care when counselling Case 2. CONCLUSION: The GPs in our sample reacted case-specifically to the patients' interest in CIM. Such responsive and patient-centred communication is a valuable resource but is often time-consuming. Adequate training and reimbursement should therefore be considered for GPs.

Person-environment fit of environmental support provided during medical consultations with older patients.

As some cognitive functions decline in old age, the ability to decide about important life events such as medical treatment is endangered. Environmental support to improve the comprehension of health-related information is therefore necessary. With a small-scale explorative approach, the present survey study aimed at investigating person-environment fit (PE-fit) of support provided during medical consultations. This fit was calculated by assessing the match between aids provided by five medical practitioners during medical consultations and aids most appreciated by the geriatric patients (N = 88). The results showed that the largest discrepancies of used and appreciated aids could be found concerning the opportunity to discuss decisions with relatives, the possibility to take notes, the use of objects, pictures and a keyword list. Female patients indicated a lower PE-fit. These findings highlight discrepancies between the use of specific aids and the wishes of patients and call for thoughtful use of aids during consultations with geriatric patients.

[Capacity to consent of people with dementia : Insights into the S2k AWMF guidelines 108-001]. / Einwilligungsfähigkeit von Menschen mit Demenz : Einblicke in die S2k-AWMF-Leitlinie 108 ­ 001.

People with dementia often require medical and nursing care and are regularly confronted with the need to make decisions in this respect; however, in practice uncertainty often exists as to whether a person with dementia is capable of providing consent, what procedures should be used to obtain informed consent, how to provide the necessary information and how capacity to consent can be assured. By providing structured practical recommendations, the S2k guidelines "Consent of persons with dementia to medical treatment" (coordinated by the Association of the Scientific Medical Societies of Germany, AWMF, registration number 108-001) provide a first attempt to summarize and update the relevant medical, legal, ethical and psychological requirements that should be satisfied in this respect. This article enables insights into the guidelines and an overview of the most important recommendations.

[Capacity to consent of people with dementia : Insights into the S2k AWMF guidelines 108-001]. / Einwilligungsfähigkeit von Menschen mit Demenz : Einblicke in die S2k-AWMF-Leitlinie 108 ­ 001.

People with dementia often require medical and nursing care and are regularly confronted with the need to make decisions in this respect; however, in practice uncertainty often exists as to whether a person with dementia is capable of providing consent, what procedures should be used to obtain informed consent, how to provide the necessary information and how capacity to consent can be assured. By providing structured practical recommendations, the S2k guidelines "Consent of persons with dementia to medical treatment" (coordinated by the Association of the Scientific Medical Societies of Germany, AWMF, registration number 108-001) provide a first attempt to summarize and update the relevant medical, legal, ethical and psychological requirements that should be satisfied in this respect. This article enables insights into the guidelines and an overview of the most important recommendations.

Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment.

Previous studies in older adults suggested beneficial effects of omega-3 fatty acid (FA) supplementation, aerobic exercise, or cognitive stimulation on brain structure and function. However, combined effects of these interventions in patients suffering from mild cognitive impairment (MCI) are unknown. Using a randomized interventional design, we evaluated the effect of combined omega-3 FA supplementation, aerobic exercise and cognitive stimulation (target intervention) versus omega-3 FA supplementation and non-aerobic exercise (control intervention) on cognitive function and gray matter volume in patients with MCI. Moreover, we analyzed potential vascular, metabolic or inflammatory mechanisms underlying these effects. Twenty-two MCI patients (8 females; 60-80years) successfully completed six months of omega-3 FA intake, aerobic cycling training and cognitive stimulation (n=13) or omega-3 FA intake and non-aerobic stretching and toning (n=9). Before and after the interventions, cognitive performance, magnetic resonance imaging of the brain at 3T (n=20), intima-media thickness of the internal carotid artery and serum markers of glucose control, lipid and B-vitamin metabolism, and inflammation were assessed. Intervention-related changes in gray matter volume of Alzheimer's disease (AD)-related brain regions, i.e., frontal, parietal, temporal and cingulate cortex were examined using voxel-based morphometry of high resolution T1-weighted images. After the intervention period, significant differences emerged in brain structure between groups: Gray matter volume decreased in the frontal, parietal and cingulate cortex of patients in the control intervention, while gray matter volume in these areas was preserved or even increased after the target intervention. Decreases in homocysteine levels in the target intervention group were associated with increases in gray matter volume in the middle frontal cortex (p=0.010). No significant differences in cognitive performance or other vascular, metabolic and inflammatory parameters were observed between groups. This pilot study provides preliminary evidence that omega-3 FA intake combined with aerobic exercise and cognitive stimulation prevents atrophy in AD-related brain regions in MCI patients, compared to omega-3 FA intake plus the control condition of stretching and toning. These promising findings should now be validated in a larger interventional trial.

Impact of leptin on memory function and hippocampal structure in mild cognitive impairment.

Metabolic changes have been suggested to contribute to dementia and its precursor mild cognitive impairment (MCI), yet previous results particularly for the "satiety hormone" leptin are mixed. Therefore, we aimed to determine if MCI patients show systematic differences in leptin, independent of sex, adipose mass, age, and glucose and lipid metabolism, and whether leptin levels correlated with memory performance and hippocampal integrity. Forty MCI patients (20 females, aged 67 years ± 7 SD) were compared to 40 healthy controls (HC) that were pair-wise matched for sex, age, and body fat. Memory performance was assessed using the auditory verbal learning test. Volume and microstructure of the hippocampus were determined using 3T-neuroimaging. Fasting serum markers of leptin, glucose and lipid metabolism, and other confounding factors were assayed. MCI patients, compared with HC, showed lower serum leptin, independent of sex, age, and body fat (P < 0.001). Glucose and lipid markers did not attenuate these results. Moreover, MCI patients exhibited poorer memory and lower volume and microstructural integrity within hippocampal subfields. While leptin and memory were not significantly correlated, mediation analyses indicated that lower leptin contributed to poorer memory through its negative effect on right hippocampus volume and left hippocampus microstructure. We demonstrated that MCI is associated with lower serum leptin independent of sex, age, body fat, glucose, and lipid metabolism. Our data further suggest that inefficient leptin signaling could partly contribute to decreases in memory performance through changes in hippocampus structure, a hypothesis that should now be verified in longitudinal studies. Hum Brain Mapp 37:4539-4549, 2016. © 2016 Wiley Periodicals, Inc.

Effects of aerobic exercise on cognitive performance and individual psychopathology in depressive and schizophrenia patients.

Cognitive deficits are core symptoms in patients with schizophrenia (SZ) and major depressive disorder (MDD), but specific and approved treatments for cognitive deterioration are scarce. Experimental and clinical evidence suggests that aerobic exercise may help to reduce psychopathological symptoms and support cognitive performance, but this has not yet been systematically investigated. In the current study, we examined the effects of aerobic training on cognitive performance and symptom severity in psychiatric inpatients. To our knowledge, to date, no studies have been published that directly compare the effects of exercise across disease groups in order to acquire a better understanding of disease-specific versus general or overlapping effects of physical training intervention. Two disease groups (n=22 MDD patients, n=29 SZ patients) that were matched for age, gender, duration of disease and years of education received cognitive training combined either with aerobic physical exercise or with mental relaxation training. The interventions included 12 sessions (3 times a week) over a time period of 4 weeks, lasting each for 75 min (30 min of cognitive training+45 min of cardio training/mental relaxation training). Cognitive parameters and psychopathology scores of all participants were tested in pre- and post-testing sessions and were then compared with a waiting control group. In the total group of patients, the results indicate an increase in cognitive performance in the domains visual learning, working memory and speed of processing, a decrease in state anxiety and an increase in subjective quality of life between pre- and post-testing. The effects in SZ patients compared with MDD patients were stronger for cognitive performance, whereas there were stronger effects in MDD patients compared with SZ patients in individual psychopathology values. MDD patients showed a significant reduction in depressive symptoms and state anxiety values after the intervention period. SZ patients reduced their negative symptoms severity from pre- to post-testing. In sum, the effects for the combined training were superior to the other forms of treatment. Physical exercise may help to reduce psychopathological symptoms and improve cognitive skills. The intervention routines employed in this study promise to add the current psychopathological and medical treatment options and could aid the transition to a multidisciplinary approach. However, a limitation of the current study is the short time interval for interventions (6 weeks including pre- and post-testing).

Compliance with CBT referral in nursing home residents diagnosed with depression: Results from a feasibility study.

Objectives: Patient-level factors that influence compliance with a recommendation for CBT in nursing home residents diagnosed with depression were identified. Methods: Within a cluster-randomized trial on stepped care for depression in nursing homes (DAVOS-study, Trial registration: DRKS00015686), participants received an intake interview administered by a licensed psychotherapist. If psychotherapy was required, patients were offered a referral for CBT. Sociodemographic characteristics, severity of depression, loneliness, physical health, antidepressant medication, prior experience with psychotherapy, and attitudes towards own aging were assessed. A binary regression determined predictors of compliance with referral. Results: Of 123 residents receiving an intake interview, 80 were recommended a CBT. Forty-seven patients (58.8 %) followed the recommendation. The binary logistic regression model on compliance with recommended CBT was significant, χ2(9) = 21.64, p = .010. Significant predictors were age (Odds Ratio (OR) = 0.9; 95 % Confidence Interval (CI) = 0.82, 0.99; p = .024) and depression (OR = 1.33; 95 % CI = 1.08, 1.65; p = .008). Conclusion: Within the implemented setting compliance rate was comparable to other age groups. Future interventions should include detailed psychoeducation on the benefits of psychotherapy on mild depressive symptoms in older age and evidence-based interventions to address the stigma of depression. Interventions such as reminiscence-based methods or problem-solving could be useful to increase compliance with referral, especially in very old patients (80+). Language barriers and a culturally sensitive approach should be considered when screening residents.

[Non-pharmacological interventions for people with dementia]. / Nichtmedikamentöse Interventionen für Menschen mit Demenz.

BACKGROUND: Non-pharmacological interventions for people with dementia are intended to improve quality of life and well-being, alleviate psychopathological and behavioral symptoms, and also offer caregivers support and opportunities to promote resilience. Against the background of the multiple failures in the field of pharmacological-therapeutic research, these approaches have become increasingly important. OBJECTIVE: An up-to-date overview of the most important non-drug interventions for people with dementia and related recommendations for therapeutic use. MATERIAL AND METHODS: Narrative review taking into account the current state of research and the recommendations of the Working Group of (German) Scientific Medical Societies (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) S3 guideline "Dementia". RESULTS AND CONCLUSIONS: The most important interventions from this therapeutic spectrum include cognitive stimulation to maintain cognitive functioning, physical activation and creative therapeutic activities to promote communication skills and social participation. In the meantime, access to these diverse psychosocial interventions has also been supplemented by digital technology. What these interventions have in common is that they are based on the individual cognitive and physical resources of those affected, improve quality of life and mood, and promote participation and self-efficacy. In addition to psychosocial interventions, nutrition-related approaches ("medical food") and non-invasive neurostimulation have recently also shown potential in the context of non-drug therapy for people with dementia.

Effectiveness of exercise interventions to improve long-term outcomes in people living with mild cognitive impairment: a systematic review and meta-analysis.

Although exercise guidelines now recommend exercise for patients with MCI, the long-term effects of exercise in patients with MCI has not been reviewed systematically. The aim was to assess (1) the effectiveness of exercise and physical activity (EXPA) interventions in improving long-term patient-relevant cognitive and non-cognitive outcomes in people with mild cognitive impairment, (2) how well the included trials reported details of the intervention, and (3) the extent to which reported endpoints were in line with patient preferences that were assessed in patient workshops. Following PRISMA guidelines, we performed a systematic review and meta-analysis including randomized controlled trials. A total of ten studies were included after searching in six electronic sources from 1995 onwards. There is a trend that 6 + -month EXPA interventions improve global cognition 12 months after initiation. Evidence on long-term effects of EXPA interventions on non-cognitive health outcomes could not be meaningfully pooled and the individual studies reported mixed results. Workshop participants considered freedom from pain and stress, mood, motivation and self-efficacy to be important, but these outcomes were rarely addressed. Too little information is available on intervention details for EXPA programs to be replicated and confidently recommended for patients with MCI. PROSPERO registration in December, 2021 (CRD42021287166).

[Non-pharmacological interventions in dementia: an overview with special consideration of digital offerings]. / Nichtpharmakologische Interventionen bei Demenz.

Non-pharmacological interventions such as cognitive therapy, physical activity, and creative art approaches are important components of appropriate care for persons with dementia and their relatives. Although relationships and interpersonal interactions undoubtedly play an important role in all these activities, digital technologies have increasingly established themselves in this area in recent years. The following article describes non-pharmacological interventions for people with dementia (based on the German AWMF S3 dementia guideline), and additionally provides examples of selected digital approaches for this particular target group. As the aim of the interventions is to support persons with dementia in living autonomously and maintaining societal and cultural participation, all the interventions share a consideration for individual resources and the promotion of available potential. Empirical evidence on digital activities remains scarce, so it is not yet possible to make clear recommendations. When using them, it should therefore be borne in mind that although they may represent a valuable supplement, they can never replace human attention. Furthermore, limitations in their practical application, such as unfamiliarity when using digital technologies or excessive demands of cognitively limited users, as well as important ethical aspects (e. g., data protections, personality rights, dignity and self-determination in old age) should not be ignored.

Effectiveness of exercise and physical activity interventions to improve long-term patient-relevant cognitive and non-cognitive outcomes in people living with mild cognitive impairment: a protocol of a systematic review and meta-analysis.

INTRODUCTION: Mild cognitive impairment (MCI) is a clinical syndrome characterised by persistent cognitive deficits that do not yet fulfil the criteria of dementia. Delaying the onset of dementia using secondary preventive measures such as physical activity and exercise can be a safe way of reducing the risk of further cognitive decline and maintaining independence and improving quality of life. The aim is to systematically review the literature to assess the effectiveness of physical activity and exercise interventions to improve long-term patient-relevant cognitive and non-cognitive outcomes in people living with MCI, including meta-analyses if applicable. METHODS AND ANALYSIS: We will systematically search five electronic databases from 1995 onward to identify trials reporting on the effectiveness of physical activity and exercise interventions to improve long-term (12+ months) patient-relevant cognitive and non-cognitive outcomes in adults (50+ years) with MCI. Screening procedures, selection of eligible full-texts, data extraction and risk of bias assessment will be performed in dual-review mode. Additionally, the reporting quality of the exercise interventions will be assessed using the Consensus on Exercise Reporting Template. A quantitative synthesis will only be conducted if studies are homogeneous enough for effect sizes to be pooled. Where quantitative analysis is not applicable, data will be represented in a tabular form and synthesised narratively. People living with MCI will be involved in defining outcome measures most relevant to them in order to assess in how far randomised controlled trials report endpoints that matter to those concerned. ETHICS AND DISSEMINATION: Results will be disseminated to both scientific and lay audiences by creating a patient-friendly video abstract. This work will inform professionals in primary care about the effectiveness of physical activity and exercise interventions and support them to make evidence-based exercise recommendations for the secondary prevention of dementia in people living with MCI. No ethical approval required. PROSPERO REGISTRATION NUMBER: CRD42021287166.

[Design and evaluation of a preclinical medical elective titled "Safety culture in healthcare: Every error counts!"] / Konzeption und Evaluation eines vorklinischen medizinischen Wahlpflichtfaches "Sicherheitskultur in der Medizin: Jeder Fehler zählt!".

INTRODUCTION: The World Health Organization has called for more importance to be attached to the subject of patient safety in medical studies. However, teaching staff are unsure when the right time is to include this topic in existing medical school curricula. The aim of this article is to present the learning objectives, design and evaluation of a two-day elective on patient safety offered in the preclinical phase of medical studies at the Faculty of Medicine, University of Frankfurt am Main. To the best of our knowledge, no existing elective on safety culture has been provided at such an early stage of medical studies in Germany. METHODS: After defining learning objectives and teaching methods, the safety culture elective was offered in the winter term 2019/20. Based on a questionnaire, a quantitative and qualitative evaluation of the students' acceptance of the elective was carried out. We also sought to investigate whether group role-play was considered an effective means of communicating the teaching content. Acceptance and rejection of the elective were evaluated on a six-point Likert scale. RESULTS: The resulting elective, consisting of topical input via film, an introductory speech, role-play and discussions, is presented. Nineteen students in the preclinical phase of their medical studies took part. Overall, the quantitative and qualitative evaluation delivered positive results (1.2±0.5), and the topic was perceived to very important. The students considered the didactic implementation and the learning objectives to be very good, and they became acquainted with different sources of error. DISCUSSION: The preclinical elective would appear to be suitable for demonstrating the importance of medical safety to medical students and teaching them how to deal with the topic constructively. It can be viewed as a best-practice example for the development of comparable learning formats at medical faculties. CONCLUSION: The results show that the preclinical phase is a suitable time to illustrate the importance of the subject of patient safety during medical studies.

Depression in the nursing home: a cluster-randomized stepped-wedge study to probe the effectiveness of a novel case management approach to improve treatment (the DAVOS project).

BACKGROUND: Depression is the second most common psychiatric illness in old people. Up to 30% of nursing home residents have minor or major depression. Although depressive disorders in old age can be improved and even cured with adequate therapy, they often go unnoticed in nursing home residents and remain untreated. This highlights a striking deficit in health care and might result not only in lower quality of life among those concerned but also in poor physical functioning, premature mortality, and increased hospitalization rates. METHODS: The aims of the interdisciplinary research project DAVOS are to implement an innovative and stepped structural case management program to improve depression treatment for nursing home residents by a modularized intervention and to assess it in terms of its effectiveness. Intervention modules are in line with recommendations given by the German national treatment guidelines for depression (S3 guidelines). Ten nursing homes in Frankfurt, Germany, will participate in the project, which aims to recruit a study population of 380. The recruitment will continue throughout the trial (open cohort). Persons (>60 years) who live in a nursing home, have no medical diagnosis of dementia, and can provide their informed consent to participate are eligible for inclusion in the study. Residents with a clinical diagnosis of dementia, alcohol or substance-related disorders, or other serious psychiatric illnesses will be excluded. DAVOS is a controlled cluster-randomized study that employs a stepped-wedge design. DISCUSSION: Our main hypothesis is that the implementation of the intervention will lead to a decline in the prevalence of depression and a reduction in depression symptoms among the home residents. In addition, we expect the intervention to have a positive impact on secondary outcomes such as level of functioning, quality of life, and social participation. The project's results can make an important contribution toward improving the health care of nursing home residents who have late-life depression. TRIAL REGISTRATION: DRKS, DRKS00015686 , Oct. 10, 2018.

Art museum-based intervention to promote emotional well-being and improve quality of life in people with dementia: The ARTEMIS project.

ARTEMIS (ART Encounters: Museum Intervention Study) is an art-based intervention designed especially for people with dementia and their care partners that involves a combination of museum visits and artistic activity. This paper reports the results of a randomized wait-list controlled study on the influence of the ARTEMIS intervention on the emotional state, well-being, and quality of life of dementia patients. People with mild-to-moderate dementia (n = 44) and their care partners (n = 44) visited the Frankfurt Städel Museum once a week on six pre-arranged occasions. The intervention consisted of six different guided art tours (60 minutes), followed by art-making in the studio (60 minutes). Independent museum visits served as a control condition. A mixed-methods design was used to assess several outcomes including cognitive status, emotional well-being, self-rated aspects of quality of life, and subjective evaluations by informal caregivers. In a pre-post-assessment, we found significant improvements in participants' self-rated quality of life (t = -3.15, p < .05). In a situational assessment of emotional well-being immediately before and after each of the museum sessions, we were able to demonstrate statistically significant positive changes with medium effect sizes (dcorr = .74-.77). Furthermore, the total Neuropsychiatric Inventory score as well as the affective (depressed mood and anxiety) and apathy subscales were significantly lower after the ARTEMIS intervention (tNPI total = 2.43; tNPI affective = 2.24; tNPI apathy = 2.52; p < .05). The results show that art museum-based art interventions are able to improve the subjective well-being, mood, and quality of life in people with dementia. This promising psychosocial approach deserves further attention in future studies and consideration in community-based dementia care programs.

Feasibility and first results of a group program to increase the frequency of cognitively stimulating leisure activities in people with mild cognitive impairment (AKTIVA-MCI).

AKTIVA-MCI is a program for patients with mild cognitive impairment (MCI) that aims to enhance participation in cognitively stimulating leisure activities. Participation in cognitively stimulating activities seems to be a potential strategy for people with MCI delaying cognitive decline for a while. In total, 35 MCI patients were enrolled in the pilot study of whom 29 completed the whole program (16 female, 71.1±7.5 years; Mini Mental Status Examination score: 28±2.2). Daily activity protocols were used to measure the frequency of participation in cognitively stimulating activities during the program (12 sessions). Additional standardized psychometric tests and questionnaires were used to assess cognition, mood, and subjective memory decline. Analyses of the daily activity protocols showed that during the intervention participants increased the frequency of several cognitively stimulating leisure activities. Comparison of pre-post data indicates no changes in cognitive status, mood, and subjective memory decline. These findings indicate that the program is suitable for patients with MCI.

Impact of Resveratrol on Glucose Control, Hippocampal Structure and Connectivity, and Memory Performance in Patients with Mild Cognitive Impairment.

In healthy older adults, resveratrol supplementation has been shown to improve long-term glucose control, resting-state functional connectivity (RSFC) of the hippocampus, and memory function. Here, we aimed to investigate if these beneficial effects extend to individuals at high-risk for dementia, i.e., patients with mild cognitive impairment (MCI). In a randomized, double-blind interventional study, 40 well-characterized patients with MCI (21 females; 50-80 years) completed 26 weeks of resveratrol (200 mg/d; n = 18) or placebo (1,015 mg/d olive oil; n = 22) intake. Serum levels of glucose, glycated hemoglobin A1c and insulin were determined before and after intervention. Moreover, cerebral magnetic resonance imaging (MRI) (3T) (n = 14 vs. 16) was conducted to analyze hippocampus volume, microstructure and RSFC, and neuropsychological testing was conducted to assess learning and memory (primary endpoint) at both time points. In comparison to the control group, resveratrol supplementation resulted in lower glycated hemoglobin A1c concentration with a moderate effect size (ANOVARMp = 0.059, Cohen's d = 0.66), higher RSFC between right anterior hippocampus and right angular cortex (p < 0.001), and led to a moderate preservation of left anterior hippocampus volume (ANOVARMp = 0.061, Cohen's d = 0.68). No significant differences in memory performance emerged between groups. This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c, preserves hippocampus volume, and improves hippocampus RSFC in at-risk patients for dementia. Larger trials with longer intervention time should now determine if these benefits can be validated and extended to cognitive function.

Vitamin B-12 concentration, memory performance, and hippocampal structure in patients with mild cognitive impairment.

BACKGROUND: Low-normal concentrations of vitamin B-12 (VitB12) may be associated with worse cognition. However, previous evidence has been mixed, and the underlying mechanisms remain unclear. OBJECTIVE: We determined whether serum VitB12 concentrations within the normal range were linked to memory functions and related neuronal structures in patients with mild cognitive impairment (MCI). DESIGN: In a cross-sectional design, we assessed 100 amnestic MCI patients (52 women; age range: 50-80 y) with low- and high-normal VitB12 concentration (median split: 304 pmol/L) for memory functions with the use of the Auditory Verbal Learning Test. MRI was performed at 3 tesla (n= 86) for the estimation of the volume and microstructure of the hippocampus and its subfields as indicated by the mean diffusivity on diffusion-weighted images. With the use of a mediation analysis, we examined whether the relation between VitB12 and memory performance was partially explained by volume or microstructure. RESULTS: MCI patients with low-normal VitB12 showed a significantly poorer learning ability (P= 0.014) and recognition performance (P= 0.008) than did patients with high-normal VitB12. Also, the microstructure integrity of the hippocampus was lower in patients with low-normal VitB12, mainly in the cornu ammonis 4 and dentate gyrus region (P= 0.029), which partially mediated the effect of VitB12 on memory performance (32-48%). Adjustments for age, sex, education, apolipoprotein E e4 status, and total homocysteine, folate, and creatinine did not attenuate the effects. CONCLUSIONS: Low VitB12 concentrations within the normal range are associated with poorer memory performance, which is an effect that is partially mediated by the reduced microstructural integrity of the hippocampus. Future interventional trials are needed to assess whether supplementation of VitB12 may improve cognition in MCI patients even in the absence of clinically manifested VitB12 deficiency. This trial was registered at clinicaltrials.gov as NCT01219244.