Short-term Medication Effect on Fall Risk in Multimorbid Inpatients with Dementia.

INTRODUCTION: Dementia increases the risk of falls and fall-related injuries, which may be caused by inappropriate medication use. To date, there is little evidence on which medications are more likely to cause falls. We therefore investigated the effects of medication use and medication changes 48 hours before falls in hospitalised patients with dementia. METHODS: This matched case-control study included 74 patients with a mean age of 83 years (38% women) who had been hospitalised for at least 7 days. Information on medications, diagnoses, disease severity, use of walking aids, falls, and demographics was collected from electronic medical records. The effects of number of medications and psychotropics, equivalent daily doses of antidepressants, antipsychotics and benzodiazepines, anticholinergic burden, medication initiation, dose change, medication discontinuation, as-needed medications, opioid use and the presence of fall-increasing diseases were examined separately for the periods 0h-24h and 24h-48h before the falls using binomial logistic regression analyses. RESULTS: Falls increased significantly with higher daily antipsychotic doses 24 hours before the fall. In addition, the rate of falls increased with higher anticholinergic burden and prevalence of medication discontinuation 24 to 48 hours before the fall. Notably, the total number of medications and psychotropic medications had no effect on the incidence of falls. DISCUSSION/CONCLUSION: With regard to the short-term effects of medication on fall risk, particular attention should be paid to the daily dose of antipsychotics, anticholinergic burden and medication discontinuation. Further studies with larger samples are needed to confirm the results of this study.

Long-term impact of resilience and extraversion on psychological distress during the COVID-19 pandemic: a longitudinal investigation among individuals with and without mental health disorders.

Background: Over the past years, the COVID-19 pandemic has caused significant disruptions in daily routines. Although the pandemic has affected almost everyone, it has been particularly challenging for people with pre-existing mental health conditions. Therefore, this study investigated the long-term impact of resilience and extraversion on psychological distress in individuals diagnosed with mental health disorders (MHD) compared to the general population. In addition, possible gender-specific differences were investigated. Methods: 123 patients with pre-existing MHD and 343 control subjects from Austria and Italy participated in three online surveys that had been conducted after the initial wave of the COVID-19 pandemic (t0), during the second lockdown in both countries (t1), and one year thereafter (t2). Participants completed standardized questionnaires on psychological distress (Brief-Symptom-Checklist), resilience (Resilience Scale), and extraversion (Big Five Inventory). A mediation model was employed to test the primary hypothesis. Possible gender-specific differences were analyzed using a moderated mediation model. Results: The prevalence of psychological distress was consistently higher in patients compared to controls (t0: 37.3% vs. 13.2%, t1: 38.2% vs 11.7%, t2: 37.4% vs. 13.1%). This between-group difference in psychological distress at the first follow-up was fully mediated by baseline resilience scores (65.4% of the total effect). During the second-follow up, extraversion accounted for 18% of the total effect, whereas resilience slightly decreased to 56% of the total effect. Gender was not a significant moderator in the model. Conclusion: Next to showing that people with MHD were particularly affected by the pandemic, these findings indicate that higher degrees of resilience and extraversion are related to less long-term psychological distress. Our findings stress the relevance of strengthening resilience and extraversion and to provide mental health support in times of crises, both to patients with MHD and the general population.

Relevance of spirituality and perceived social support to mental health of people with pre-existing mental health disorders during the COVID-19 pandemic: a longitudinal investigation.

BACKGROUND: The COVID-19 pandemic and related measures have negatively impacted mental health worldwide. The main objective of the present longitudinal study was to investigate mental health in people living in Tyrol (Austria) and South Tyrol (Italy) during the COVID-19 pandemic and to report the prevalence of psychological distress among individuals with versus those without pre-existing mental health disorders (MHD) in the long-term (summer 2020-winter 2022). Here, we specifically focus on the relevance of spirituality and perceived social support in this regard. METHODS: 161 individuals who had been diagnosed with MHD and 446 reference subjects participated in this online survey. Electronic data capture was conducted using the Computer-based Health Evaluation System and included both sociodemographic and clinical aspects as well as standardized questionnaires on psychological distress, spirituality, and the perception of social support. RESULTS: The prevalence of psychological distress was significantly higher in individuals with MHD (36.6% vs. 12.3%) and remained unchanged among both groups over time. At baseline, the perception of social support was significantly higher in healthy control subjects, whereas the two groups were comparable in regards of the subjective relevance of faith. Reference subjects indicated significantly higher spiritual well-being in terms of the sense of meaning in life and peacefulness, which mediated in large part the between-group difference of psychological distress at follow-up. Notably, both faith and the perception of social support did not prove to be relevant in this context. CONCLUSIONS: These findings point to a consistently high prevalence of psychological distress among people suffering from MHD and underscore the prominent role of meaning in life and peacefulness as a protective factor in times of crisis. Therapeutic strategies that specifically target spirituality may have a beneficial impact on mental health.

A Qualitative Literature Search and Pilot Study of Online Support Groups for Patients With Dementia and Their Carers.

The ever-growing group of people living with dementia (PLWD) and their relatives face great challenges. The Covid 19 pandemic has once again placed a particular challenge on this vulnerable group. What started a decade earlier with telephone-based support groups experienced a real push during the pandemic in the form of video-based self-help services. The aim of this qualitative literature search in MEDLINE, EMBASE, CINAHL, and PsycINFO with keywords related to online, support group, caregiver, and dementia was to collect the reported experiences by the end of 2022. Peer reviewed journal papers were included when published and written in English. After the joint decision of two reviewers, it was decided to only include studies that were published in Medline. The results of the literature search are compared with experiences of the participants in a presentation group that was transformed into an online group at the time of the COVID-19 pandemic via Zoom. In search yielded a total of 129 articles. 113 articles described different types of interventions, 30 of which had a randomized design. The qualitative literature search showed on the one hand a high interest in online support groups but on the other hand that the effectiveness and efficacy in randomized trials is much less clear. In addition, we investigated the assessments and experiences of the participants in a presentation group that was transformed into an online group at the time of the COVID-19 pandemic via Zoom. This study demonstrates that PLWD and carers on virtual group meetings can express significant emotive capacity and enhanced connectivity with one another despite a diagnosis of mild to moderate dementia. Further research on entry criteria, concerns about online support services in general and necessary support for use is essential to develop the time- and location-independent possibility of video-based online self-help into an important form of support for both PLWD and their caregivers as an additional support option independent of exceptional pandemic situations.

C9orf72 repeat length might influence clinical sub-phenotypes in dementia patients.

BACKGROUND: C9orf72 repeat expansions have been observed in a wide variety of neurodegenerative disorders. The cut-off between normal and pathogenic alleles is not well established as repeat sizing methods are often semi-quantitative. However, intermediate alleles might influence disease prevalence and phenotype, as seen for other repeat expansion disorders. We aimed to further delineate the prevalence of small, intermediate and expanded C9orf72 alleles and elucidate their potential influence on the disease phenotype. METHODS: DNA derived from patients (n = 1804) and healthy individuals (n = 643) was obtained from multiple collectives in Austria. Genotyping was performed using a two-step PCR assay followed by Southern blotting. RESULTS: 3.4% of clinically diagnosed frontotemporal dementia (FTD; n = 5/147) cases and 0.8% of clinically diagnosed Alzheimer's disease (AD; n = 5/602) cases were carriers of a pathological C9orf72 repeat expansion. A significantly earlier disease onset was detected in expansion carriers compared to non-carriers in the FTD and AD cohorts (median 50 years, range 39-64 vs. median 64 years, range 36-92, p = 0.018 and median 63 years, range 54-71 vs. median 74 years, range 45-92, p = 0.006, respectively). C9orf72 intermediate alleles were significantly associated with cerebellar symptoms (p = 0.0004) and sensory deficits in the dementia cohort (p = 0.01). CONCLUSIONS: C9orf72 repeat expansion carriers showed earlier disease onset compared to non-carriers with clinical diagnosis of FTD and AD. Furthermore, C9orf72 intermediate repeats might modify the phenotypic expression in dementia.

Saliva tau and phospho-tau-181 measured by Lumipulse in patients with Alzheimer's disease.

Alzheimer's disease (AD) is a severe neurodegenerative brain disorder. The determination of beta-amyloid (Aß)-40, -42, total tau, and phospho-tau-181 (pTau181) in cerebrospinal fluid (CSF) using Lumipulse technology has been established as biomarkers for AD in recent years. As CSF collection is an invasive procedure, one aims to find biomarkers in blood or other human fluids, such as saliva. In the present study, we aim to measure these markers in human saliva. Using Salivettes, we collected saliva samples from healthy controls (n = 27), patients with AD dementia (n = 44), mild cognitive impairment (MCI) (n = 45), depression (n = 31), and 21 blinded samples, all older than 60 years. Lumipulse technology with a G600II was used to detect all four biomarkers. Our data show that the levels of total protein were highly variable and thus biomarker levels were corrected to 1 mg/ml of total protein. Saliva Aß-40 and -42 were not detectable, because it was not recovered from the Salivettes. However, saliva total tau (577 ± 134 pg/mg, n = 22) and phospho-tau-181 (9.7 ± 1.3 pg/mg, n = 21) could be analyzed by Lumipulse technology. Saliva total tau levels were significantly decreased in patients with AD (≤ 300 pg/mg protein), while pTau181 levels (≥ 18 pg/mg protein) were significantly enhanced in patients with MCI compared to controls. Laboratory diagnosis with a cut-off of ≥ 18 pg/mg protein pTau181 (for MCI) and ≤ 300 pg/mg protein tau (for AD) for blinded samples could diagnose MCI and AD with an accuracy of 71.4%. Despite these initial promising results, the findings must be replicated in larger cohorts, and several technical problems due to saliva processing must be solved and Salivettes should not be used.

Addiction in the time of COVID-19: Longitudinal course of substance use, psychological distress, and loneliness among a transnational Tyrolean sample with substance use disorders.

Introduction: Next to an increased use of alcohol, the current pandemic has been associated with increased psychological distress among the general population. Research on its effects on individuals suffering from substance use disorders (SUD) is scarce. This study aimed at expanding the existing literature on this topic with a focus on the impact of loneliness and perceived social support. Methods: Sixty-eight people diagnosed with SUD according to ICD-10 from the Austrian state of Tyrol and from the Italian Province of South Tyrol who had been treated in a psychiatric hospital in 2019 and one hundred and thirty-six matched reference subjects of the same regional background participated in an online survey. Sociodemographic variables and scores on the Brief Symptom Checklist, the Three-Item Loneliness Scale, and the Multidimensional Scale of Perceived Social Support were collected at baseline and 5 months thereafter. Baseline took place after the first wave, while follow-up largely coincided with the second wave of the pandemic. Results: Among both patients and the matched reference group, substance use as a means to feel better facing the pandemic rose and predicted higher levels of psychological distress. Patients were less likely to receive specific care at follow-up than at baseline and presented with a significantly higher prevalence of clinically relevant psychological distress and loneliness than the matched reference group at both assessment times. Among both groups, psychological burden remained unchanged over time. Perceived social support was generally significantly higher in the matched reference group than in patients. Loneliness and, to a lesser degree, low perceived social support predicted psychological distress. Conclusion: These findings emphasize the need of preventive and educational measures regarding substance use behavior for both individuals suffering from SUD and those without mental health disorders.

Platelet TAU is Associated with Changes in Depression and Alzheimer's Disease.

BACKGROUND: Platelets (thrombocytes) are small anuclear cells that play an important role in blood clotting. They are activated and dysfunctional in brain disorders, such as Alzheimer's disease (AD) and depression. Platelets express the amyloid-precursor protein (APP) and release beta-amyloid40 into the blood. Recent evidence reports that platelets also express the microtubule-associated protein tau. In this study, we further characterized the molecular appearance of tau and examined its alterations in patients with neurocognitive impairment. METHODS: Platelets were isolated from patients with AD, mild cognitive impairment (MCI) or depression and compared to healthy controls. Subsequently, FACS analysis was employed to characterize platelets for platelet surface P-selectin (CD62P). In order to enhance the detection levels, samples were pooled (15 samples per group) and analyzed by Lumipulse Assay, Western blots, and mass spectrometry. RESULTS: Tau is expressed in human platelets and tau levels were decreased in platelets isolated from patients with AD and depression. Additionally, phospho-tau-181 was slightly increased in patients with depression. We show that tau is highly fragmented (20-40 kDa) in the platelet extracts using Western blot analysis. The mass spectrometry data did not show a clear identification of tau in the pooled platelet samples. CONCLUSIONS: Our data reveal that tau is found in platelets, possibly in a highly fragmented form. Tau levels may be used as a potential diagnostic approach to differentiate AD and depression from healthy controls.

Effects of dynamic bedroom lighting on measures of sleep and circadian rest-activity rhythm in inpatients with major depressive disorder.

Bright light therapy is an effective treatment option for seasonal and non-seasonal affective disorders. However up to now, no study has investigated effects of dynamic bedroom lighting in hospitalized patients with major depression. A bedroom lighting system, which automatically delivered artificial dawn and dusk and blue-depleted nighttime lighting (DD-N lighting) was installed in a psychiatric ward. Patients with moderate to severe depression were randomly assigned to stay in bedrooms with the new lighting or standard lighting system. Patients wore wrist actimeters during the first two treatment weeks. Additionally, hospitalization duration and daily psychotropic medication were retrieved from patients' medical charts. Data from thirty patients, recorded over a period of two weeks, were analyzed. Patients under DD-N lighting generally woke up earlier (+ 20 min), slept longer (week 1: + 11 min; week 2: + 27 min) and showed higher sleep efficiency (+ 2.4%) and shorter periods of nighttime awakenings (- 15 min). In the second treatment week, patients started sleep and the most active 10-h period earlier (- 33 min and - 64 min, respectively). This pilot study gives first evidence that depressed patients' sleep and circadian rest/activity system may benefit from bedroom lighting when starting inpatient treatment.

Parasympathetic cardiac control during attentional focus and worry in major depressive disorder.

Worry, which refers to uncontrollable chains of thoughts and images with negative affective load, is a transdiagnostic symptom of various mental disorders including major depressive disorder (MDD). Current theories relate excessive worry to deficient top-down control of automatically occurring perseverative thinking. This study investigated parasympathetic cardiac control in MDD in the context of worry and cognitive control. Heart rate variability (HRV) was recorded, in the high frequency (HF) and low frequency (LF) bands, in 36 MDD patients and 36 healthy controls while they performed a breathing focus task. The task included two phases during which participants' ability to concentrate on their breathing was assessed before and after an instructed worry phase. In addition to higher self-reported worry, MDD patients exhibited lower HF and LF HRV at rest, and lower LF HRV during the task than controls. MDD was also associated with impaired breathing concentration ability, more negative and neutral thought intrusions, more negative mood during breathing focus and increased stress during instructed worry. In the total sample, LF HRV correlated negatively with self-reported worry and negative thought intrusions, and positively with mood ratings. The reduction of HRV confirms the notion of low parasympathetic cardiac control in MDD. Moreover, low HRV represents a correlate of blunted prefrontal activity and impaired cognitive control that characterize the disorder. Impaired cognitive control may exacerbate worry, which is in turn involved in the genesis of aversive emotional states and maintenance of MDD.

Disorder-Specific Profiles of Self-Perceived Emotional Abilities in Schizophrenia and Major Depressive Disorder.

Deficits in social cognition are a core feature of neuropsychiatric disorders. The purpose of this study was to compare profiles of self-perceived abilities across the core domains of emotional functioning between patients with schizophrenia (n = 22), major depressive disorder (n = 31) and healthy participants (n = 43) with the Self-report Emotional Ability Scale (SEAS). Profile analyses were used to explore group differences in the overall level of self-perceived effectiveness of emotional functioning and in the patterns in which the four functions of emotion perception and regulation in the intra- and inter-personal domains are arranged to each other. Both patient groups showed significantly lower overall levels of self-perceived emotional functioning compared to healthy controls. Most importantly, we found significant differences between patient groups in their profile patterns. Patients with schizophrenia indicated experiencing difficulties in all investigated domains, but the profile pattern largely matched that of healthy individuals. Instead, the profile of patients with depression was much more accentuated, showing lower perceived effectiveness of emotion perception and regulation in the intra-personal domain compared to inter-personal functions. Our results of disorder-specific emotional deficits may have profound implications for early screening and identification of at-risk populations as well as recovery-oriented interventions.

Mental health in individuals with severe mental disorders during the covid-19 pandemic: a longitudinal investigation.

Research on the long-term mental health impact of the COVID-19 pandemic across mental disorders is limited, and information on the impact of public health policy measures with varying strictness is missing. This study therefore aimed at investigating psychological distress among residents of Tyrol (Austria) and South Tyrol (Italy) at the early stages of the pandemic and 5 months thereafter and examined how sociodemographic, protective, and risk factors relate to change over time. One hundred and fifteen people with severe mental illness (SMI; schizophrenia spectrum disorder, bipolar disorder, major depressive disorder with psychotic features) or major depressive disorder without psychotic features (MDD) and 481 community controls without mental disorders participated in an online survey. Next to the collection of sociodemographic and COVID-19 related variables, the Brief Symptom Checklist, the Resilience Scale, the Multidimensional Scale of Perceived Social Support, the Three-Item Loneliness Scale, and the Multidimensional State Boredom Scale-Short Form were used to assess psychological distress, resilience, perceived social support, loneliness, and boredom. Levels of psychological symptoms and the prevalence of psychological distress were significantly higher in individuals with MDD compared to the other two groups, and Italian participants were more prone to anxiety than those from Austria. Psychological distress was predicted by a lower degree of both resilience and perceived social support as well as loneliness and boredom. Notably, the prevalence of clinically relevant psychological symptoms remained unchanged among each group over time. These results underscore the relevance of tailored prevention and mitigation strategies to meet the specific needs of people both with and without mental disorders.

The Impact of Resilience and Extraversion on Psychological Distress, Loneliness, and Boredom During the COVID-19 Pandemic: A Follow-Up Study Among the General Population of Tyrol, Austria.

Background: The Covid-19 pandemic and related measures represent an enormous burden on mental health. The aim of this study was to investigate longitudinal changes in psychological distress, loneliness, boredom, and resilience over the course of the pandemic and to examine the associations between resilience and extraversion at baseline (summer 2020) and psychological distress, loneliness, and boredom at 5-month-follow-up. Methods: Residents of Tyrol (≥18a) completed an online survey on psychological distress, loneliness, boredom, resilience, and extraversion by using the Brief-Symptom-Checklist, the Three-Item Loneliness Scale, the Multidimensional State Boredom Scale-Short Form (MSBS-SF), the Resilience Scale, and the Extraversion subscale of the Big Five Inventory. Results: Of the 961 baseline participants, 384 took part in the follow-up survey. The percentage of study participants with striking psychological distress remained the same. Similarly, resilience did not change from baseline to follow-up, whereas the number of those experiencing moderate loneliness increased significantly. In contrast, at follow-up, severe loneliness was detected in significantly less people. Boredom decreased significantly over time. A moderate negative association was detected between baseline resilience and psychological distress, loneliness, and boredom at follow-up, and a weak but still significant negative association between extraversion and these outcomes. Discussion: These findings indicate that a subset of the general population consistently suffers from high levels of psychological distress and point to the protective effects of resilience and extraversion in this context. They reemphasize the importance of prevention and mitigation strategies to address these public health problems.

The Mediating Role of Resilience and Extraversion on Psychological Distress and Loneliness Among the General Population of Tyrol, Austria Between the First and the Second Wave of the COVID-19 Pandemic.

Background: During the first 3 weeks of the COVID-19 pandemic, the federal state of Tyrol, Austria had one of the strictest curfews in Austria and worldwide. The aim of the current study was to investigate the assumingly protective role of resilience and extraversion and its impact on mental health following such an uncertain and unpredictable situation. Methods: Between the first and the second wave of the pandemic, adult residents of Tyrol were invited to participate in an online survey. Next to the assessment of sociodemographic and COVID-19-related variables the Brief-Symptom-Checklist, the Three-Item Loneliness Scale, the Resilience Scaled, and the Big Five Inventory were used to assess psychological distress, loneliness, resilience, and extraversion. Mediation analysis was used to investigate the role of resilience and extraversion in the context of age-, sex-, and partnership- related differences in psychological distress and loneliness. Results: One hundred and forty-five participants took part in the survey (68.2% female). Overall, psychological distress and severe loneliness were more often detected in women and singles. They also were less resilient, while men and singles presented with a lower degree of extraversion. Study participants under the age of 30 experienced severe loneliness more frequently than older people, whereas psychological distress, resilience, and extraversion were comparable between age groups. Resilience significantly mediated the relationship between both study participants' sex and partnership situation on one hand and psychological distress and severe loneliness on the other. In addition, extraversion significantly mediated the relationship between participants' partnership situation and psychological distress. Discussion: Our findings suggest that women, singles, and young people may be particularly affected by the measures and sequelae of the COVID-19 pandemic. Interventions promoting resilience and extraversion among these groups are urgently needed to foster mental health. Ideally, they can be utilized at home in case of renewed mobility restrictions or quarantine in the future.

Decision Making under Risk in Patients Suffering from Schizophrenia or Depression.

Studies have reported difficulties in decision making for patients with schizophrenia or depression. Here, we investigated whether there are differences between schizophrenia patients, depressed patients, and healthy individuals (HC) when decisions are to be made under risk and cognitive flexibility is required. We were also interested in the relationships between decision making, cognitive functioning, and disease severity. Thirty HC, 28 schizophrenia patients, and 28 depressed patients underwent structured clinical assessments and were assessed by the Positive and Negative Syndrome Scale or Hamilton Rating Scale. They performed the Probability-Associated Gambling (PAG) Task and a neuropsychological test battery. Both patient groups obtained lower scores than HC in memory and executive function measures. In the PAG task, relative to HC, depressed patients made slower decisions but showed a comparable number of advantageous decisions or strategy flexibility. Schizophrenia patients were slower, riskier, and less flexible compared to HC. For them, the decision making behavior correlated with the symptom severity. In both groups, decision making scores correlated with memory and executive function scores. Patients with schizophrenia or depression may have difficulties under risk when quick and flexible decisions are required. These difficulties may be more pronounced in patients who have marked cognitive deficits or severe clinical symptoms.

Pain and Associated Neuropsychiatric Symptoms in Patients Suffering from Dementia: Challenges at Different Levels and Proposal of a Conceptual Framework.

Old age is critically associated with multi-morbidity, chronic pain, and high risk for dementia. Recognizing and treating pain is very much dependent on language comprehension and production. Both may be impaired in dementia. Moreover, neuropsychiatric symptoms may interact with pain perception. The main aims of the present article were 1) to identify key areas for future research to elucidate the relation between pain and associated neuropsychiatric symptoms in dementia, and 2) to provide a conceptual framework for ameliorating the clinical process of recognizing, assessing, and managing pain in non-communicating patients with advanced dementia.

Psychological Distress, Loneliness, and Boredom Among the General Population of Tyrol, Austria During the COVID-19 Pandemic.

Background: COVID-19-related mental health problems are considered a public health challenge. The aim of this study was to investigate psychological distress, loneliness, and boredom among the general population of the federal state of Tyrol, Austria. Methods: Residents of Tyrol aged ≥ 18 years were recruited via dissemination of a link through social media and other advertisements and invited to complete an online survey from June 26th to August 20th, 2020. Next to the collection of sociodemographic and COVID-19 related variables the Brief Symptom Checklist (BSCL), the Three-Item Loneliness Scale (TILS), and the Multidimensional State Boredom Scale-Short Form (MSBS-SF) were used to assess psychological distress, loneliness, and boredom. Results: 961 participants took part in the survey (68.3% woman). Of these, 14.4% were burdened from psychological distress (BSCL), 22.6% reached a TILS score ≥ 7 and were therefore classified as severely lonely, and boredom levels lay by a mean of 25.9 ± 11.0 points in the MSBS-SF (range: 7-56). Women, singles, low-income people as well as those who were unemployed were significantly more often affected by all of the selected outcomes compared to the remaining sample and they had significantly more frequently consumed alcohol or other substances since the outbreak of the pandemic in order to feel better. In addition, young and middle-aged adults were particularly burdened by loneliness and boredom. Discussion: Our findings identify vulnerable groups and factors associated with higher psychological distress, loneliness, and boredom in the context of the pandemic. In order to prevent mental health problems it will be critical to identify options of maintaining social contacts and remaining active despite pandemic-related restrictions.

Dietary spermidine improves cognitive function.

Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan-extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that dietary spermidine passes the blood-brain barrier in mice and increases hippocampal eIF5A hypusination and mitochondrial function. Spermidine feeding in aged mice affects behavior in homecage environment tasks, improves spatial learning, and increases hippocampal respiratory competence. In a Drosophila aging model, spermidine boosts mitochondrial respiratory capacity, an effect that requires the autophagy regulator Atg7 and the mitophagy mediators Parkin and Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement of olfactory associative learning. This suggests that the maintenance of mitochondrial and autophagic function is essential for enhanced cognition by spermidine feeding. Finally, we show large-scale prospective data linking higher dietary spermidine intake with a reduced risk for cognitive impairment in humans.

Plasma phosphatidylcholines and vitamin B12/folate levels are possible prognostic biomarkers for progression of Alzheimer's disease.

OBJECTIVES: In clinical practice it is important to identify patients suffering from mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD). The purpose of this study is to investigate whether lipid metabolites and vitamin B12 and folate levels are effective biomarker for an accurate prediction of MCI-to-AD conversion. METHODS: During the standard diagnostic assessment at our memory clinic 48 cognitively healthy subjects and MCI patients were recruited. These participants were followed up after 7-9 years. Blood was collected, various biochemical markers (including vitamin B12 and folate) analysed and plasma lipids were measured using the AbsoluteIDQ p150 Kit. RESULTS: There was no significant change in lipid levels in controls converting to MCI. However, we found significant changes in five lipids in converters from controls to AD. Interestingly, also two lipids were altered when MCI re-converted to controls. Vitamin B12 levels were not affected by conversion but folate levels significantly decreased in MCI-AD conversion. CONCLUSIONS: Taken together, our study provides evidence that some plasma lipids are significantly altered in subjects converting to AD. Future studies will investigate whether the peripheral lipid changes correspond with changes in the brain during the course of the disease. Although this is a small study, there are indications that lipids may be suitable as prognostic markers.

Features of autonomic cardiovascular control during cognition in major depressive disorder.

Previous research has suggested reduced parasympathetic cardiac regulation during cognitive activity in major depressive disorder (MDD). However, little is known about possible abnormalities in sympathetic control and cardiovascular reactivity. This study aimed to provide a comprehensive analysis of autonomic cardiovascular control in the context of executive functions in MDD. Thirty six MDD patients and 39 healthy controls participated. Parameters of sympathetic (pre-ejection period, PEP) and parasympathetic control (high and low frequency heart rate variability, HF HRV, LF HRV; and baroreflex sensitivity, BRS) as well as RR interval were obtained at rest and during performance of executive function tasks (number-letter task, n-back task, continuous performance test, and Stroop task). Patients, as compared to controls, exhibited lower HF HRV and LF HRV during task execution and smaller shortenings in PEP and RR interval between baseline and tasks. They displayed longer reaction times during all conditions of the tasks and more omission errors and false alarms on the continuous performance test. In the total sample, on-task HF HRV, LF HRV and BRS, and reactivity in HF HRV, LF HRV, and PEP, were positively associated with task performance. As performance reduction arose independent of executive function load of the tasks, the behavioral results reflect impairments in attention and processing speed rather than executive dysfunctions in MDD. Abnormalities in cardiovascular control during cognition in MDD appear to involve both divisions of the autonomic nervous system. Low tonic parasympathetic control and blunted sympathetic reactivity imply reduced physiological adjustment resources and, by extension, provide suboptimal conditions for cognitive performance.