Why do we climb mountains? An exploration of features of behavioural addiction in mountaineering and the association with stress-related psychiatric disorders.

Common knowledge implies that individuals engaging in outdoor sports and especially in regular and extreme mountaineering are exceptionally healthy and hardened. Physical activity in outdoor environments has a positive effect on physical and mental health. However, regular and/or extreme mountaineering might share similarities with behavioural addictions and could thus also have a negative impact on health. In this cross-sectional web-based questionnaire study, we collected data on exercise and mountaineering addiction (Exercise Addiction Inventory; original and adapted version for mountaineering; Exercise Dependence Scale adapted version for mountaineering). Further surveyed parameters included mountaineering habits, Risk-Taking Inventory, Sensation-Seeking/Emotion Regulation/Agency Scale (SEAS), resilience, self-perceived stress, physical activity in metabolic units and mental health. Comparisons were performed between individuals with symptoms of addiction to mountaineering (MA) and individuals without symptoms of addiction to mountaineering or sports in general (CO) using non-parametric analyses. We analysed data from 335 participants, n = 88 thereof with addiction to mountaineering (MA) and n = 247 control participants (CO). The MA group scored significantly higher with regards to self-perceived stress (p < 0.001) and included a significantly higher number of individuals affected by symptoms of depression (p < 0.001), symptoms of anxiety (p < 0.001), symptoms of eating disorders (p < 0.001), alcohol abuse or dependence (p < 0.001), illicit drug abuse (p = 0.050), or current and history of psychiatric disorders (p < 0.001). Individuals with MA showed higher values in all SEAS subscales as well as increased risk-taking (p < 0.001). Regular and extreme mountaineering can display features of a behavioural addiction and is associated with psychiatric disorders. Behavioural addiction in mountaineering is associated with higher levels of sensation-seeking, emotion regulation, and agency, as well as increased risk-taking.

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.

What Characterizes Depression in Old Age? Results from the Bruneck Study.

INTRODUCTION: Depression in old age is associated with functional disabilities, cognitive impairment, lower self-rated quality of life, and increased mortality. The aim of the study was to reveal the prevalence of depression and to investigate the characteristics of patients treated with antidepressants. METHODS: We analyzed data from the Bruneck Study 2010. All participants completed a clinical examination, cognitive screening, the 30-item Geriatric Depression Scale (GDS) (cutoff score of>8 to define relevant depressive symptoms), and the World Health Organization quality of life questionnaire (WHO-QoL). Group differences were calculated using binary logistic regression analysis. RESULTS: Out of 456 participants (mean age of 73.1±8.2 years), 22.1% showed depressive symptoms, and out of these, 30% were taking antidepressants. The depressed group compared to the GDS ≤8 group showed significantly lower WHO-QoL (p<0.001) and Mini Mental State Examination (p=0.015) score. Further, 13% of the latter compared to the GDS>8 group received antidepressants, and these had a lower WHO-QoL score (p<0.033). DISCUSSION: Depressive symptoms are frequent in the elderly population. Our results confirm the negative influence of depressive symptoms on cognition and quality of life. Patients with somatic comorbidities are likely to receive more antidepressant medication.

Reduced beta-amyloid sensitivity for platelet-monocyte aggregates in EDTA blood of alzheimer patients.

Alzheimer´s disease (AD) is a severe neurodegenerative brain disorder characterized by beta-amyloid plaques, Tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. Besides that, alterations in monocytes and platelets have been reported in the blood of Alzheimer patients. In the present study, we measured circulating levels of platelet-monocyte aggregates in EDTA blood of cognitively healthy participants and 40 AD patients, and examined their changes induced by stimulation with beta-amyloid peptides. We measured CD14, CD62P, and CD42a using fluorescence-activated cell scanning (FACS) analysis. Our data show that the levels of circulating monocyte-platelet aggregates were not different between healthy controls and AD patients. However, incubation with beta-amyloid-40, -42, and pyroglutamate-beta-amyloid increased the platelet-monocyte aggregation in healthy subjects, but not AD patients. Our data conclude that the interaction between monocytes and platelets is not altered in whole blood of AD patients, but their sensitivity toward beta-amyloid peptides is decreased. There might be a critical link between the interaction of platelets and monocytes in AD, which has to be explored in further studies.

Executive Dysfunctions Predict Self-Restricted Driving Habits in Elderly People with or without Alzheimer's Dementia.

Introduction The purpose of this study was to elucidate the impact of specific cognitive functions on self-restricted driving habits in healthy elderly drivers and patients suffering from mild cognitive impairment (MCI) and Alzheimer's dementia (AD). Method Our study population included 35 cognitively healthy controls, 10 MCI patients, and 16 patients with AD. All participants completed a neuropsychological examination and a self-reported questionnaire assessing driving habits and patterns. Results In challenging driving conditions, patients with MCI or AD showed significantly more driving self-restriction than healthy subjects (effect size d=1.06, p=0.007). Ordinal regression analysis across the entire group revealed that deficits in executive functions and reaction had a higher impact on driving restriction (p=0.002) than deficits in memory functions (p=0.570). Additionally, our data showed that 40% of patients with mild to moderate AD still drive in challenging conditions. Discussion Our results illustrate that elderly individuals use self-imposed driving restrictions as compensatory strategies. These restrictions increase with cognitive decline mainly in the field of executive functions, but they do not change once patients convert from MCI to AD.

Use of Benzodiazepines in Alzheimer's Disease: A Systematic Review of Literature.

BACKGROUND: Benzodiazepines are frequently prescribed in patients with Alzheimer's disease. Unfortunately, studies evaluating their benefits and risks in these patients are limited. METHODS: Clinical trials focusing on the effect of benzodiazepines on cognitive functions, disease progression, behavioral symptoms, sleep disturbances, and the general frequency of benzodiazepine use were included in this review. Published articles from January 1983 to January 2015 were identified using specific search terms in MEDLINE and PubMed Library according to the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology initiative. RESULTS: Of the 657 articles found, 18 articles met predefined selection criteria and were included in this review (8 on frequency, 5 on cognitive functions, 5 on behavioral and sleep disturbances). The frequency of benzodiazepine use ranged from 8.5% to 20%. Five studies reported accelerated cognitive deterioration in association with benzodiazepine use. Two studies reported clinical efficacy for lorazepam and alprazolam to reduce agitation in Alzheimer's disease patients. No evidence was found for an improvement of sleep quality using benzodiazepines. CONCLUSION: This systematic review shows a relatively high prevalence of benzodiazepine use but limited evidence for clinical efficacy in Alzheimer's disease patients. However, there is a paucity of methodologically high quality controlled clinical trials. Our results underscore a need for randomized controlled trials in this area.

Probable RBD and association with neurodegenerative disease markers: A population-based study.

BACKGROUND: The prevalence of rapid eye movement sleep behavior disorder (RBD) and its association with markers of neurodegeneration in the general population are poorly defined. METHODS: We assessed the prevalence of probable RBD defined by two validated questionnaires, the RBD Screening Questionnaire (RBDSQ) and the Innsbruck RBD-Inventory (RBD-I), and studied its associations with clinical and imaging markers for neurodegeneration in the Bruneck Study cohort aged 60 y or older. RESULTS: Of the 456 participants without Parkinson's disease, 4.6% (RBDSQ; 95%CI, 3.0%-7.0%) and 7.7% (RBD-I; 95%CI, 5.6%-10.5%) had probable RBD. Probable RBD diagnosed with either of the questionnaires was associated with hyposmia (trend; P < 0.1), anxiety (P < 0.05), depression (P < 0.05), antidepressant use (P < 0.05), and self-reported non-motor symptoms (P < 0.01), specifically, dribbling saliva, memory problems, apathy, concentration problems, and anxiety. CONCLUSIONS: Our findings may provide a basis for future studies intending to identify cohorts at risk for Lewy body diseases through screening of the general elderly population for RBD.

COVID-19 restrictions promoted the newly occurring loneliness in older people - a prospective study in a memory clinic population.

Introduction: A high burden and many negative outcomes for older people were associated with the COVID-19 pandemic. Social isolation and loneliness are prevalent health problems impacting well-being and quality of life and may have increased due to pandemic-related restrictions. Methods: This study investigate the influence of the COVID-19 pandemic on loneliness in people visiting a mem40ory clinic between March 2020 and September 2022. We conducted a prospective, single-center, questionnaire-based observational follow-up study to assess potential predictors of newly occurring, pandemic-related loneliness. Next to a newly developed COVID-19 questionnaire, a comprehensive neuropsychological test battery, the Neuropsychiatric Inventory and the Geriatric Depression Scale were used. Results: In total 426 people (mean age: 76.48 years, 12.9% cognitively intact, 33.1% diagnosed with Mild Cognitive Impairment, 49.8% diagnosed with dementia, and 4.2% diagnosed with depression) completed the COVID-19 questionnaire at baseline and 166 at follow-up. Newly occurring loneliness was indicated by 22.3% of baseline participants and by 24.1% of follow-up participants. Results of logistic regression analysis showed that living alone (OR 5.452) and having less contact with friends (OR 2.771) were most predictive of the occurrence of loneliness. The use of digital communication media as an alternative strategy for social interaction was lowest in dementia patients (6-13%). Discussion: In conclusion, personal contacts and a close friendship network appear to be more decisive to prevent loneliness in older people than does the use of digital communication media. However, promoting an intensified use of digital communication media may be useful to counteract loneliness, especially in dementia patients.

Sleep features and long-term incident neurodegeneration: a polysomnographic study.

STUDY OBJECTIVES: Sleep is altered early in neurodegenerative diseases (NDDs) and may contribute to neurodegeneration. Long-term, large sample-size studies assessing NDDs association with objective sleep measures are scant. We aimed to investigate whether video-polysomnography (v-PSG)-based sleep features are associated with long-term NDDs incidence. METHODS: Retrospective cohort study of patients referred 2004-2007 to the Sleep Disorders Unit, Neurology, Medical University Innsbruck, Austria. All patients ≥ 18 years undergoing v-PSG and without NDDs at baseline or within 5 years were included. Main outcome was NDDs diagnosis ≥5 years after v-PSG. RESULTS: Of 1454 patients assessed for eligibility, 999 (68.7%) met inclusion criteria (68.3% men; median age 54.9 (IQR 33.9-62.7) years). Seventy-five patients (7.5%) developed NDDs and 924 (92.5%) remained disease-free after a median of 12.8 (IQR 9.9-14.6) years. After adjusting for demographic, sleep, and clinical covariates, a one-percentage decrease in sleep efficiency, N3-, or rapid-eye-movement (REM)-sleep was associated with 1.9%, 6.5%, or 5.2% increased risk of incident NDDs (HR 1.019, 1.065, and 1.052). One-percentage decrease in wake within sleep period time represented a 2.2% reduced risk of incident NDDs (HR 0.978). Random-forest analysis identified wake, followed by N3 and REM-sleep percentages, as the most important feature associated with NDDs diagnosis. Additionally, multiple sleep features combination improved discrimination of incident NDDs compared to individual sleep stages (concordance-index 0.72). CONCLUSIONS: These findings support contribution of sleep changes to NDDs pathogenesis and provide insights into the temporal window during which these differences are detectable, pointing to sleep as early NDDs marker and potential target of neuroprotective strategies.

Psychosocial state after bariatric surgery is associated with the serotonin-transporter promoter polymorphism.

BACKGROUND: Bariatric surgery is the method of choice in the treatment of morbid obesity. Different genotypes of the serotonin transporter gene (5-HTT) are known to impact the prevalence of psychiatric disorders and the psychosocial state in obese individuals. In this study, we examined the influence of the 5-HTTLPR polymorphism on physiologic and psychosocial measures in morbidly obese women after bariatric surgery. METHODS: We investigated women 1-5 years after bariatric surgery using a semi-structured interview and the Beck Depression Inventory, the Moorhead-Ardelt Quality of life questionnaire, the NEO-Five Factor Inventory and a Resilience scale. The 5-HTTLPR polymorphism (s/s, s/l, l/l) was genotyped using mouth swabs. The influence of genotype on outcome variables was analyzed by independent t test and analysis of covariance corrected for possible confounders. RESULTS: 64 women were enrolled in this study between January 2004 and September 2009. Significantly lower quality of life and higher depression, neuroticism and resilience scores were found in homozygous s-allele carriers of the 5-HTTLPR polymorphism than in l-allele carriers. Except for neuroticism, other factors (age, education, year of surgery, weight before surgery and method of surgery) did not affect the results. We found no influence of genotype on weight loss, current weight or weight before surgery. CONCLUSION: Quality of life, mood, and resilience but not weight loss after bariatric surgery are negatively influenced by the s-allele of the 5-HTTLPR polymorphism.

Consequences and Perception of the COVID-19 Pandemic on Patients and Caregivers in an Austrian Memory Clinic Population One Year After Pandemic Onset.

BACKGROUND: The COVID-19 pandemic was associated with high mortality and negative consequences for patients with Alzheimer's disease or dementia and their caregivers. Memory clinics play an important role in enabling early dementia diagnosis and providing support for patients and their caregivers. OBJECTIVE: This study investigates the impact of the COVID-19 pandemic and its restrictions on patients of a memory clinic and their caregivers between March 2020 and March 2021. METHODS: We conducted a prospective, single-center, questionnaire-based, observational study to assess consequences and perception of the COVID-19 pandemic on emotion, cognitive function, social living, areas of care, and information retrieval. RESULTS: Results of 255 participants' (mean age 76.78, SD 8.9; 12% cognitively intact, 33% mild cognitive impairment, 55% dementia) and 203 caregivers' COVID-19 questionnaires (valid response rate 71%) could be included in the study. Participants reported a prevalence of psychological symptoms associated with the pandemic between 3-20%. Caregivers living outside compared to those living with the participant reported higher rates of new onset or worsening of neuropsychiatric symptoms in participants since pandemic onset. Patients with dementia showed the lowest use of digital communication before (15.7%) and after (17.1%) pandemic onset in the diagnostic groups. CONCLUSION: The COVID-19 pandemic frequently led to social isolation and reduced cognitive stimulation due to restrictions in elderly persons with cognitive deficits resulting in negative effects on emotional and social levels. We hypothesize that the implementation and sensitization with digital communication in clinical routine could provide a useful tool to counteract these negative effects.

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.

Generation of the human induced pluripotent stem cell line (IBKMOLi002-A) from PBMCs of a patient carrying the heterozygous L271H mutation of the voltage-gated calcium channel subunit Cav1.3-encoding CACNA1D gene.

Congenital hyperinsulinemic hypoglycemia (HH) is the most frequent cause of persistent and recurrent hypoglycemia. Peripheral mononuclear blood cells (PBMCs) from a patient diagnosed with HH, alongside autism-spectrum-disorder (ASD), carrying a heterozygous c.812 T>A (L271H) mutation in the voltage-gated calcium channel subunit Cav1.3-encoding gene CACNA1D, were reprogrammed into induced pluripotent stem cells (iPSC). The CACNA1D L271H iPSC (IBKMOLi002-A) exhibit a normal karyotype, high expression of pluripotency-associated markers and the capacity to differentiate into cells of all three germ layers. We provide a novel patient-specific iPSC line, allowing to study HH, ASD, the associated neurodevelopmental disorder as well as CACNA1D-associated channelopathies in general.

Chemical Replacement of Noggin with Dorsomorphin Homolog 1 for Cost-Effective Direct Neuronal Conversion.

The direct conversion of adult human skin fibroblasts (FBs) into induced neurons (iNs) represents a useful technology to generate donor-specific adult-like human neurons. Disease modeling studies rely on the consistently efficient conversion of relatively large cohorts of FBs. Despite the identification of several small molecular enhancers, high-yield protocols still demand addition of recombinant Noggin. To identify a replacement to circumvent the technical and economic challenges associated with Noggin, we assessed dynamic gene expression trajectories of transforming growth factor-ß signaling during FB-to-iN conversion. We identified ALK2 (ACVR1) of the bone morphogenic protein branch to possess the highest initial transcript abundance in FBs and the steepest decline during successful neuronal conversion. We thus assessed the efficacy of dorsomorphin homolog 1 (DMH1), a highly selective ALK2-inhibitor, for its potential to replace Noggin. Conversion media containing DMH1 (+DMH1) indeed enhanced conversion efficiencies over basic SMAD inhibition (tSMADi), yielding similar ßIII-tubulin (TUBB3) purities as conversion media containing Noggin (+Noggin). Furthermore, +DMH1 induced high yields of iNs with clear neuronal morphologies that are positive for the mature neuronal marker NeuN. Validation of +DMH1 for iN conversion of FBs from 15 adult human donors further demonstrates that Noggin-free conversion consistently yields iN cultures that display high ßIII-tubulin numbers with synaptic structures and basic spontaneous neuronal activity at a third of the cost.

Influence of serotonin transporter genotype and catechol-O-methyltransferase Val158Met polymorphism on recognition of emotional faces.

Monoamines, such as serotonin, dopamine, and norepinephrine, play a crucial role in the regulation of emotion processing and mood. In this study, we investigated how polymorphisms of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) influence emotion recognition abilities. We recruited 88 female undergraduate students and assessed 5-HTT genotype and the COMT Val158Met polymorphism. The subjects completed two computerized tasks: The Penn Emotion Recognition Test (ER40) and the Penn Emotion Acuity Test (PEAT). For the ER40, we found that s-allele carriers performed significantly worse in the recognition of happy faces, but did better in the recognition of fearful faces, compared with homozygous l-carriers of the 5-HTT gene. Neither 5-HTT nor COMT genotypes influenced the ability to discriminate between different intensities of sadness or happiness on the PEAT. Moreover, there was no significant interaction between the two polymorphisms in their effect on performance on the ER40 or the PEAT.

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.

[Position paper of the Austrian Alzheimer Association (Österreichische Alzheimer Gesellschaft, ÖAG) : Effects of the COVID-19 pandemic in Austria on people with dementia and their care environment-problem areas, recommendations, and strategies]. / Positionspapier der Österreichische Alzheimer Gesellschaft (ÖAG) : Auswirkungen der COVID-19-Pandemie in Österreich auf Menschen mit Demenz und deren Betreuungsumfeld ­ Problemfelder, Empfehlungen und Strategien.

Older adults are particularly affected by the current COVID-19 (SARS-CoV-2) pandemic. The risk of dying from COVID-19 increases with age and is often associated with pre-existing health conditions. Globally, more than 50 million-in Austria currently approximately 140,000 people-suffer from dementia. The co-occurrence of dementia as a "pandemic of old age" together with the COVID-19 pandemic has a double impact on persons living with dementia and their caregivers. The COVID-19 pandemic poses major challenges for individuals with dementia and their caregivers: (1) People with dementia have limited access to information on COVID-19, may have difficulties with protective measures such as wearing masks and in remembering safety regulations. (2) People with dementia live alone or with their family, or are institutionalized. To reduce the chance of infection among older people in nursing homes, Austrian local authorities have banned visitors to nursing homes and long-term care facilities and implemented strict social-distancing measures. As a result, older people lost face-to-face contact with their family members, became isolated and social activities stopped. Consequently, anxiety, stress and serious concerns about infections among staff in nursing homes increased and they developed signs of exhaustion and burnout during the full lockdown of the facilities. Thus, due to the emerging COVID-19 crisis, the Austrian Alzheimer Association (Österreichische Alzheimer Gesellschaft, ÖAG) and international societies developed recommendations to support people living with dementia and their caregivers on various issues of physical and mental health.

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.

Cannabinoid as Beneficial Replacement Therapy for Psychotropics to Treat Neuropsychiatric Symptoms in Severe Alzheimer's Dementia: A Clinical Case Report.

Alzheimer's Dementia (AD) is a devastating neurodegenerative disease that affects approximately 17% of people aged 75-84. Neuropsychiatric symptoms (NPS) such as delusions, agitation, anxiety, and hallucinations are present in up to 95% of patients in all stages of dementia. To date, any approved and effective pharmacological interventions for the treatment of NPS are still not available. We describe a clinical case of a female patient diagnosed with AD with continuous cognitive decline and dementia-related behavioral symptoms. Between 2008 and 2019, the patient was examined half-yearly at the memory clinic of the Medical University of Innsbruck. At each visit, cognitive state and pharmacological treatment were evaluated. In addition, NPs were assessed by using the neuropsychiatric inventory (NPI). In 2018, the patient progressed to severe AD stage and presented with progressive NPs (anxiety, suspected delusions, agitation, aggressive behavior, and suspected pain due to long immobility). Consequently, off-label treatment with low-dose dronabinol was initiated, which facilitated a reduction of psychopharmacological treatment from six to three psychotropics. At the same time, the patient's emotional state improved, while disruptive behavior, aggression, and sedation decreased significantly. This case report underpins the need for randomized, controlled trials to explore the effect of cannabinoid receptor agonists on behavioral and psychological symptoms in patients with severe AD.

Specific Neuropsychiatric Symptoms Are Associated with Faster Progression in Alzheimer's Disease: Results of the Prospective Dementia Registry (PRODEM-Austria).

BACKGROUND: Neuropsychiatric symptoms (NPS) occur frequently in the course of Alzheimer's disease (AD) and are suspected to be associated with a faster dementia progression. Numerous reports have defined specific subsyndromes, summarized in clusters of items of the Neuropsychiatric Inventory (NPI). OBJECTIVE: This study investigated the influence of specific NPI subsyndromes and clinical patient characteristics on dementia progression. METHODS: Data of the prospective registry on dementia in Austria (PRODEM) were retrospectively analyzed. Cognitive functioning was determined at baseline and 2 yearly follow-up visits using the Mini-Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's dementia neuropsychological test battery (CERAD). To assess NPS, the NPI was used: NPI items were classified in three subsyndromes (psychotic cluster, behavioral cluster, emotional cluster). RESULTS: Out of the 662 included patients (mean age 76.4±8.4 years), 43% completed follow-up visits for two years. Significant correlation between higher scores in all three subsyndromes and worse cognitive performance were found for MMSE score, naming, and verbal fluency. Results of linear mixed model analysis revealed lower age and higher scores in the psychotic cluster as significant predictors of changes in MMSE with time. CONCLUSION: In this study, we report the influence of psychotic subsyndromes and lower age on faster MMSE decline in early AD. These results emphasize the importance of not only assessing but also differentiating neuropsychiatric symptoms in subsyndromes in the early stages of AD as a possible predictor of disease progression.