Major depression mistaken as frontotemporal dementia due to PET scan.

Clinicians should be aware that the hypometabolism associated with depression can mimic frontotemporal dementia on PET.

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial.

BACKGROUND: Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response. METHODS: In this trial, outpatients (N = 96, aged 22-65 years) meeting the diagnostic criteria for at least moderate depression (Montgomery and Aasberg Depression Rating Scale score ≥ 20) will be enrolled prospectively and receive ten, once-a-day sessions of either active iTBS or sham iTBS to the left DLPFC, localized via a neuronavigation system. Participants may have any degree of treatment resistance. Prior to stimulation, participants will undergo a thorough safety screening and a brief diagnostic assessment, genetic analysis of brain-derived neurotropic factor, 5-HTTLPR and 5-HT1A, and cerebral MRI assessments. A selection of neuropsychological tests and questionnaires will be administered prior to stimulation and after ten stimulations. An additional follow-up will be conducted 4 weeks after the last stimulation. The first participant was enrolled on June 4, 2022. Study completion will be in December 2027. The project is approved by the Regional Ethical Committee of Medicine and Health Sciences, Northern Norway, project number 228765. The trial will be conducted according to Good Clinical Practice and published safety guidelines on rTMS treatment. DISCUSSION: The aims of the present trial are to investigate the antidepressive effect of a 10-session iTBS protocol on moderately depressed outpatients and to explore the factors that can explain the reduction in depressive symptoms after iTBS but also a poorer response to the treatment. In separate, but related work packages, the trial will assess how clinical, cognitive, brain imaging and genetic measures at baseline relate to the variability in the antidepressive effects of iTBS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05516095. Retrospectively registered on August 25, 2022.

The effects of exceeding low-risk drinking thresholds on self-rated health and all-cause mortality in older adults: the Tromsø study 1994-2020.

BACKGROUND: Based on findings of increasing alcohol consumption in older adults, it is important to clarify the health consequences. Using data from the Tromsø study, we aimed to investigate the relationship between different levels of alcohol consumption in old adulthood and self-rated health trajectories and all-cause mortality. METHODS: This is an epidemiological study utilizing repeated measures from the Tromsø study cohort. It allows follow-up of participants from 1994 to 2020. A total of 24,590 observations of alcohol consumption were made in older adults aged 60-99 (53% women). PRIMARY OUTCOME MEASURES: Self-rated health (SRH) and all-cause mortality. SRH was reported when attending the Tromsø study. Time of death was retrieved from the Norwegian Cause of Death Registry. The follow-up time extended from the age of study entry to the age of death or end of follow-up on November 25, 2020. PREDICTOR: Average weekly alcohol consumption (non-drinker, < 100 g/week, ≥100 g/week). We fitted two-level logistic random effects models to examine how alcohol consumption was related to SRH, and Cox proportional hazards models to examine its relation to all-cause mortality. Both models were stratified by sex and adjusted for sociodemographic factors, pathology, biometrics, smoking and physical activity. In addition, all the confounders were examined for whether they moderate the relationship between alcohol and the health-related outcomes through interaction analyses. RESULTS: We found that women who consumed ≥100 g/week had better SRH than those who consumed < 100 g/week; OR 1.85 (1.46-2.34). This pattern was not found in men OR 1.18 (0.99-1.42). We identified an equal mortality risk in both women and men who exceeded 100 g/week compared with those who consumed less than 100 g/week; HR 0.95 (0.73-1.22) and HR 0.89 (0.77-1.03), respectively. CONCLUSIONS: There was no clear evidence of an independent negative effect on either self-rated health trajectories or all-cause mortality for exceeding an average of 100 g/week compared to lower drinking levels in this study with up to 25 years follow-up. However, some sex-specific risk factors in combination with the highest level of alcohol consumption led to adverse effects on self-rated health. In men it was the use of sleeping pills or tranquilisers and ≥ 20 years of smoking, in women it was physical illness and older age.

A four-month home-based tDCS study on patients with Alzheimer's disease.

In the present open-label study, our first aim was to study the tolerability and feasibility of long-term treatment with transcranial direct current stimulation (tDCS) and the second aim was to measure whether the treatment led to cognitive improvement. Participants with AD used a tDCS home-treatment kit inducing a low current (2 mA) via two scalp electrodes 30 minutes daily for 4 months. A total of 8 participants were recruited. The treatment technique was manageable for the participants and their spouses, and no troublesome side effects were reported. No significant effects of treatment were found after 4 months.

Sex differences in at-risk drinking and associated factors-a cross-sectional study of 8,616 community-dwelling adults 60 years and older: the Tromsø study, 2015-16.

BACKGROUND: Alcohol consumption among older adults is on the rise, which may be an increasing public health concern. The proportion of older adults who drink above defined low-risk drinking limits, associated characteristics and the sex distribution of at-risk drinking vary across countries. The aims of this study were to (i) estimate the prevalence of at-risk drinking among older adults in Norway, (ii) investigate factors associated with at-risk drinking, and (iii) examine sex differences in alcohol consumption in the context of sociodemographic and selected health characteristics. METHOD: A cross-sectional study based on Tromsø 7 (2015-16), an ongoing population-based cohort survey. Data were retrieved from participants aged 60 and older (60-99 years) who answered questions about alcohol consumption (n = 8,616). Sex-stratified logistic regressions were used to assess the association between three at-risk drinking outcome variables, and sociodemographic and selected health characteristics. The outcome variables were operationalized using the Alcohol Use Disorders Identification Test (AUDIT), and Alcohol Consumption Questions (AUDIT-C), i.e. - cut off for at risk drinking, drinking any 6+ in the past year, and any alcohol problems. RESULTS: The overall prevalence of at-risk drinking among those aged 60-99 years was equal in women and men; 44% and 46%, respectively. At-risk drinking was strongly associated with a higher level of education, with OR 2.65 (CI 2.28-3.10) in women and OR 1.73 (CI 1.48-2.04) in men. CONCLUSIONS: Almost half of older adults in Norway exceeded sex- and older adult-specific at-risk drinking thresholds. Our findings suggest some differences in factors associated with at-risk drinking between women and men. Explicitly, at-risk drinking was associated with very good health, living with a spouse or partner, and having adequate social support in women, while it was associated with the use of sleeping pills in men. Our findings suggest that women exceed at-risk drinking thresholds with better health, while men exceed at-risk drinking thresholds regardless of good or poor health.

High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer's Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position.

BACKGROUND: The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer's disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. OBJECTIVE: To measure the effect of individualized HD-tDCS in AD patients. METHODS: Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient's brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. RESULTS: Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. CONCLUSION: HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

The changing alcohol drinking patterns among older adults show that women are closing the gender gap in more frequent drinking: the Tromsø study, 1994-2016.

BACKGROUND: As the population of older adults continues to grow, changes in alcohol consumption are important to monitor because an increase may have public health consequences. Rates of alcohol use vary with geographical location. The aim of this study was to examine trends in alcohol consumption among older adults in a geographically defined area in Norway, especially changing sex differences in drinking patterns over a 22-year period. METHODS: Repeated cross-sectional survey (in 1994-95, 2007-08, and 2015-16) of a general population of older adults. Eligible for this study were 20,939 participants (aged 60-99 years). The data were analysed using generalized estimating equations, stratified by age and sex. Alcohol consumption and drinking patterns were assessed, using an adaptation of the AUDIT-C. RESULTS: Between 1994 and 2016, there has been a significant increase in the proportion of current drinkers among older adults. Furthermore, the probability of frequent drinking (alcohol consumption at least twice weekly) increased significantly between 1994 and 2016, particularly among older women; OR 8.02 (CI 5.97-10.79) and OR 5.87 (CI 4.00-8.63) in the age groups 60-69 and 70+ respectively for women, and OR 4.13 (CI 3.42-4.99) and OR 3.10 (CI 2.41-3.99), in the age groups 60-69 and 70+ respectively for men. The majority of older adults drank small amounts of alcohol on typical drinking days, but there was an increasing probability of drinking three drinks or more on each occasion over the study period, except among women aged 70+ years. CONCLUSIONS: Among older adults in Norway, alcohol consumption in terms of frequency and quantity on typical drinking days has increased considerably from 1996 to 2016. This change is in the opposite direction of what has been reported among younger adults. The gap between women and men in frequent drinking has been markedly narrowed, which indicate that women's drinking patterns are approaching those of men. This may involve a need to change alcohol policy in Norway to more targeted interventions aimed at older people.

Can accelerated transcranial direct current stimulation improve memory functions? An experimental, placebo-controlled study.

The aim of this study was to investigate whether transcranial Direct Current Stimulation (tDCS) could improve verbal memory functions in healthy old and younger participants. We hypothesized that active tDCS led to significantly improved memory function, compared to placebo tDCS. Forty healthy participants (20 old and 20 younger participants) were included in the study. We applied a novel stimulation protocol, where six sessions of anodal tDCS were administrated during two consecutive days. Each tDCS session lasted 30 min. The current intensity was 2mA and the stimulation area was the left temporal lobe at T3 in the 10-20 EEG system. Immediate recall, delayed recall and recognition memory were assessed with California Verbal Learning Test II (CVLT-II) and executive functions were assessed with the Trail Making Test (TMT) before the first tDCS session and after the last tDCS session. Half of the participants received placebo tDCS, whereas the other half received active tDCS. We did not reveal any significant differences between active and placebo tDCS in memory functions. However, there was a significant difference between active and placebo tDCS in executive function measured by the Trail Making Test (TMT). This experimental study failed to reveal significant differences between active and placebo accelerated tDCS for verbal memory functions. However, accelerated tDCS was found to be well-tolerated in this study.

Changes in cytokines during treatment of elderly, hospitalized psychiatric patients - a naturalistic study.

Immunological abnormalities have been demonstrated in several psychiatric disorders. Predominantly, studies have focused on younger adults, and research on elderly psychiatric in-patients is scant. In this naturalistic study, we investigated changes in cytokine levels during the treatment of diagnostically unselected elderly psychiatric in-patients, and whether these changes could be related to clinical outcomes. Clinical variables, demographic data, lifestyle data, and blood samples, including 27 plasma cytokines representing a broad spectrum of inflammatory mediators, were collected from 81 patients, 60 years and older, at admission and discharge. A subgroup of 49 patients also completed a self-reported clinical, psychiatric status form, indicating their level of recovery during hospitalisation. Statistical analyses demonstrated that a broad range of cytokines fell during treatment, and the fall was associated with clinical improvement, irrespective of psychiatric and somatic diagnoses. Exploiting cytokines as biomarkers of clinical traits might to be of limited use in a general population of elderly psychiatric in-patients as the field stands now.

Cytokine profiles and diagnoses in elderly, hospitalized psychiatric patients.

BACKGROUND: There is a paucity of studies on inflammatory markers in elderly psychiatric patients. Hence, our study was undertaken to investigate cytokines as biomarkers in diagnostically unselected elderly patients admitted to a psychiatric hospital. METHODS: Demographic data, clinical data and blood samples, including 27 cytokines, were collected from 98 patients above 60 years, consecutively admitted to a psychiatric hospital in Tromsø, Norway (69°N). RESULTS: The most common diagnosis was Recurrent depressive disorder (26.5%), the second most common was dementia in Alzheimer's disease (20.4%). The most frequent somatic disease was cardiovascular disease (28%). No statistical association (p < 0.01) was found between cytokines and gender, age, BMI, anti-inflammatory drugs, psychotropic drugs, reason for admittance, smoking, vitamin supplements, alcohol consumption, length of stay, somatic disease (present/not-present) or psychiatric diagnoses. However, when allocating patients to two groups, depression and no depression, we found higher levels of 10 cytokines in the no depression group (FDR-p < 0.0044). Possibly, this could in part be explained by the higher prevalence of cardiovascular disease (CVD) and dementia in the no depression group, as these factors were significant predictors of patients being categorized as not depressed in a logistic regression. In addition, other unknown factors might have contributed to the association between no depression and elevated cytokines. On the other hand, the high level of psychiatric and somatic comorbidity in the study population may have led to increased levels of cytokines in general, possibly diluting the potential effect of other factors, depression included, on the cytokine levels. The size of the study, and particularly the size of the subgroups, represents a limitation of the study, as do the general heterogeneity and the lack of a control group. CONCLUSIONS: There was no significant difference in cytokine levels between various psychiatric diagnoses in hospitalized elderly psychiatric patients. This indicates that previous findings of correlations between cytokines and various psychiatric disorders in highly selected adult cases might not be applicable to elderly psychiatric inpatients. Further immunological studies are needed on gerontopsychiatric patients in general and gerontopsychiatric patients with specific disorders, preferably with patients that are physically healthy. TRIAL REGISTRATION: Retrospectively registered in the ISRCTN registry study, with study ID ISRCTN71047363 .

Can 8 months of daily tDCS application slow the cognitive decline in Alzheimer's disease? A case study.

This case study presents a patient with early-onset Alzheimer`s disease, who applied transcranial direct current stimulation (tDCS) daily for 8 consecutive months. This was a much higher frequency than previous tDCS studies. Neuropsychological assessments were conducted before the first tDCS session, after 5 months and after 8 months. After 8 months, the patient's immediate recall improved with 39%, whereas delayed recall improved 23%. Overall, the results revealed that patient's cognitive functions were stabilized. There may be slight possibility that tDCS could slow the cognitive decline in Alzheimer`s disease. This should be investigated in clinical trials.

Transcranial direct current stimulation as a memory enhancer in patients with Alzheimer's disease: a randomized, placebo-controlled trial.

BACKGROUND: The purpose of this study was to assess the efficacy of transcranial direct current stimulation (tDCS) on verbal memory function in patients with Alzheimer's disease. METHODS: We conducted a randomized, placebo-controlled clinical trial in which tDCS was applied in six 30-minute sessions for 10 days. tDCS was delivered to the left temporal cortex with 2-mA intensity. A total of 25 patients with Alzheimer's disease were enrolled in the study. All of the patients were diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria. Twelve patients received active stimulation, and thirteen patients received placebo stimulation. The primary outcome measure was the change in two parallel versions of the California Verbal Learning Test-Second Edition, a standardized neuropsychological memory test normalized by age and gender. The secondary outcome measures were the Mini Mental State Examination, clock-drawing test, and Trail Making Test A and B. RESULTS: Changes in the California Verbal Learning Test-Second Edition scores were not significantly different between the active and placebo stimulation groups for immediate recall (p = 0.270), delayed recall (p = 0.052), or recognition (p = 0.089). There were nonsignificant differences in score changes on the Mini Mental State Examination (p = 0.799), clock-drawing test (p = 0.378), and Trail Making Test A (p = 0.288) and B (p = 0.093). Adverse effects were not observed. CONCLUSIONS: Compared with placebo stimulation, active tDCS stimulation in this clinical trial did not significantly improve verbal memory function in Alzheimer's disease. This study differs from previous studies in terms of the stimulation protocol, trial design, and application of standardized neuropsychological memory assessment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02518412 . Registered on 10 August 2015.

Risk of malnutrition and zinc deficiency in community-living elderly men and women: the Tromsø Study.

OBJECTIVE: Elderly people may be at particular risk of Zn deficiency due to an increased prevalence of malnutrition. The aim of the present study was to evaluate the Zn status in community-living elderly people at risk of malnutrition. DESIGN: Cross-sectional population-based survey. Individuals at risk of malnutrition were identified by the Malnutrition Universal Screening Tool. Zn status was assessed by measuring serum Zn. Logistic regression was performed to evaluate the association between the risk of malnutrition and Zn deficiency. SETTING: Municipality of Tromsø, Norway. SUBJECTS: Random sample of 743 men and 778 women aged 65-87 years. RESULTS: Zn deficiency was found in 10.1% of the participants, including 13.1% of the men and 7.3% of the women. Among the men and women at risk of malnutrition, 31.0% and 12.7%, respectively, had Zn deficiency. In a model adjusted for age, gender, serum albumin and smoking status, Zn deficiency was positively associated with the risk of malnutrition (OR=2.2; 95% CI 1.3, 3.6). CONCLUSIONS: Overall, Zn deficiency was found in one out of ten community-living elderly people and was associated with the risk of malnutrition. Our results encourage the assessment of Zn status in elderly people at risk of malnutrition, with a special emphasis on elderly men.

Vitamin D deficiency is common in psychogeriatric patients, independent of diagnosis.

BACKGROUND: Previous studies have found an association between psychiatric disorders and vitamin D deficiency, but most studies have focused on depression. This study aimed to establish the prevalence of vitamin D deficiency in elderly patients with a wider range of psychiatric diagnoses. METHOD: The study included elderly patients (>64 years) referred to a psychiatric hospital in Northern Norway and a control group from a population survey in the same area. An assessment of psychiatric and cognitive symptoms and diagnoses was conducted using the Montgomery and Aasberg Depression Rating Scale, the Cornell Scale for Depression in Dementia, the Mini Mental State Examination, the Clockdrawing Test, and the Mini International Neuropsychiatric Interview (MINI+), as well as clinical interviews and a review of medical records. The patients' mean level of 25-hydroxyvitamin D (25(OH)D) and the prevalence of vitamin D deficiency were compared with those of a control group, and a comparison of vitamin D deficiency across different diagnostic groups was also made. Vitamin D deficiency was defined as 25(OH)D <50 nmol/L (<20 ng/ml). RESULTS: The mean levels of 25(OH)D in the patient group (n = 95) and the control group (n = 104) were 40.5 nmol/L and 65.9 nmol/L (p < 0.001), respectively. A high prevalence of vitamin D deficiency was found in the patient group compared with the control group (71.6% and 20.0%, respectively; p < 0.001). After adjusting for age, gender, season, body mass index, and smoking, vitamin D deficiency was still associated with patient status (OR: 12.95, CI (95%): 6.03-27.83, p < 0.001). No significant differences in the prevalence of vitamin D deficiency were found between patients with different categories of psychiatric diagnoses, such as depression, bipolar disorders, psychosis, and dementia. CONCLUSION: Vitamin D deficiency is very common among psychogeriatric patients, independent of diagnostic category. Even though the role of vitamin D in psychiatric disorders is still not clear, we suggest screening for vitamin D deficiency in this patient group due to the importance of vitamin D for overall health.

[Depression or Alzheimer-type dementia?]. / Depresjon eller demens av Alzheimers type?

BACKGROUND: The prevalence of depression and Alzheimer-type dementia in the elderly will increase, they may have similar symptoms, making it difficult to distinguish between these two conditions, and both conditions may occur simultaneously in one and the same patient. This article provides an overview of symptoms and findings that may be important for distinguishing depression from Alzheimer-type dementia. METHOD: The article is based on a structured search in PubMed of a discretionary selection of studies, as well as the authors' own clinical experience. RESULTS: Depression and Alzheimer-type dementia may share a number of cognitive and affective symptoms, such as amnesia, attention deficit, impaired emotional reactions and a general lack of initiative. Mapping disease progression and daily functioning, information from next of kin, neuropsychological tests, biomarkers and diagnostic imaging of the brain may be helpful in differentiating the diagnoses. INTERPRETATION: Depression and Alzheimer-type dementia in elderly patients can be established by a GP, preferably including an assessment of disease progression, daily functioning, information-gathering from next of kin and cognitive screening. If the GP's examination fails to provide unambiguous answers, or if a young patient is involved, he or she should be referred to the specialist health services.

Zinc deficiency is common in several psychiatric disorders.

BACKGROUND: Mounting evidence suggests a link between low zinc levels and depression. There is, however, little knowledge about zinc levels in older persons with other psychiatric diagnoses. Therefore, we explore the zinc status of elderly patients suffering from a wide range of psychiatric disorders. METHODS: Clinical data and blood samples for zinc analyzes were collected from 100 psychogeriatric patients over 64 of age. Psychiatric and cognitive symptoms were assessed using the Montgomery and Aasberg Depression Rating Scale, the Cornell Scale for Depression in Dementia, the Mini-Mental State Examination, the Clockdrawing Test, clinical interviews and a review of medical records. In addition, a diagnostic interview was conducted using the Mini International Neuropsychiatric Interview instrument. The prevalence of zinc deficiency in patients with depression was compared with the prevalence in patients without depression, and the prevalence in a control group of 882 older persons sampled from a population study. RESULTS: There was a significant difference in zinc deficiency prevalence between the control group (14.4%) and the patient group (41.0%) (χ(2) = 44.81, df = 1, p<0.001). In a logistic model with relevant predictors, zinc deficiency was positively associated with gender and with serum albumin level. The prevalence of zinc deficiency in the patient group was significantly higher in patients without depression (i.e. with other diagnoses) than in patients with depression as a main diagnosis or comorbid depression (χ(2) = 4.36, df = 1, p = 0.037). CONCLUSIONS: Zinc deficiency is quite common among psychogeriatric patients and appears to be even more prominent in patients suffering from other psychiatric disorders than depression. LIMITATIONS: This study does not provide a clear answer as to whether the observed differences represent a causal relationship between zinc deficiency and psychiatric symptoms. The blood sample collection time points varied in both the control group and the patient group. No data regarding zinc supplementation were collected.