Effects of intermittent fasting on cognitive health and Alzheimer's disease.

OBJECTIVE: Caloric restriction by intermittent fasting produces several metabolic changes, such as increased insulin sensitivity and use of ketone bodies as energy sources. In humans, intermittent fasting has been studied in hypertension, diabetes, and related conditions, but, to date, not as a strategy to reduce the risk of emergent dementia. In this scoping review, the relevance of intermittent fasting as a potential preventive intervention for Alzheimer's dementia is explored. BACKGROUND: The beneficial effects of calorie restriction have been documented in animals and humans. Decreased oxidative stress damage and attenuated inflammatory responses are associated with intermittent fasting. These changes have a favorable impact on the vascular endothelium and stress-induced cellular adaptation. RESULTS: Physiological alterations associated with fasting have profound implications for pathological mechanisms associated with dementias, particularly Alzheimer's disease. Compared with ad libitum feeding, caloric restriction in animals was associated with a reduction in ß-amyloid accumulation, which is the cardinal pathological marker of Alzheimer's disease. Animal studies have demonstrated synaptic adaptations in the hippocampus and enhanced cognitive function after fasting, consistent with these theoretical frameworks. Furthermore, vascular dysfunction plays a crucial role in Alzheimer's disease pathology, and intermittent fasting promotes vascular health. CONCLUSIONS: These observations lead to a hypothesis that intermittent fasting over the years will potentially reverse or delay the pathological process in Alzheimer's disease.

Tau, ß-Amyloid, and Glucose Metabolism Following Service-Related Traumatic Brain Injury in Vietnam War Veterans: The Australian Imaging Biomarkers and Lifestyle Study of Aging-Veterans Study (AIBL-VETS).

Traumatic brain injury (TBI) is common among military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer's disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 National Institute on Aging - Alzheimer's Association (NIA-AA) research framework, by measuring tau, ß-amyloid, and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI. Seventy male Vietnam war veterans-40 with TBI (age 68.0 ± 2.5 years) and 30 controls (age 70.1 ± 5.3 years)-with no prior diagnosis of dementia or mild cognitive impairment underwent ß-amyloid (18F-Florbetaben), tau (18F-Flortaucipir), and fluorodeoxyglucose (18F-FDG) PET. The TBI cohort included 15 participants with mild, 16 with moderate, and nine with severe injury. ß-Amyloid level was calculated using the Centiloid (CL) method and tau was measured by standardized uptake value ratios (SUVRs) using the cerebellar cortex as reference region. Analyses were adjusted for age and APOE-e4. The findings were validated in an independent cohort from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DOD ADNI) study. There were no significant nor trending differences in ß-amyloid or tau levels or 18F-FDG uptake between the TBI and control groups before and after controlling for covariates. The ß-amyloid and tau findings were replicated in the DOD ADNI validation cohort and persisted when the Australian Imaging Biomarkers and Lifestyle study of aging-Veterans study (AIBL-VETS) and DOD ADNI cohorts were combined (114 TBI vs. 87 controls in total). In conclusion, no increase in the later life accumulation of the neuropathological markers of AD in veterans with a remote history of TBI was identified.

Risk of Dementia in Posttraumatic Stress Disorder.

Several studies have investigated the risk of dementia in posttraumatic stress disorder (PTSD) using a varying methodology. Epidemiological studies have found an increased risk of dementia with PTSD in Vietnam veterans as well as the general population. Laboratory studies reported the accelerated formation of ß-amyloid and tau, which represent the primary pathology of Alzheimer's dementia in animal models of PTSD. These investigations were conducted against a background of cognitive impairment and atrophy of the hippocampus and certain cortical areas in patients with PTSD. Very few studies have investigated the pathological basis in humans for the reported association of PTSD with dementia. This important gap in the literature has recently been partly addressed by very few studies that estimated the burden of ß-amyloid and tau. The PET studies did not show an association between PTSD and the specific pathology of Alzheimer's disease or signs of neurodegenerative diseases underlying other dementia syndromes. Another study demonstrated decreased plasma ß-amyloid load and increased plasma ß-amyloid 42/40 ratio in PTSD without PET evaluation. While PTSD is associated with an increased risk of dementia syndrome in general, there is no convincing evidence that it causes or accelerates the pathology of Alzheimer's disease, which causes the most common type of dementia. Factors that may account for the association between PTSD and a clinical diagnosis of dementia are discussed in this review.

Electroconvulsive Therapy in Mania: A Review of 80 Years of Clinical Experience.

Resistance to pharmacological agents is commonly encountered in the treatment of acute episodes of mania. In contemporary practice guidelines, electroconvulsive therapy (ECT), once a widely used standalone intervention for mania, is no longer considered a first-line treatment. Stigma, logistics, and ethical factors constrain ECT administration in this condition and lead to its underutilization. However, the past three decades have produced promising research regarding the use of ECT in mania. Randomized controlled trials, albeit in limited numbers, the adoption of ultrabrief ECT, examination of the safety and efficacy of combining ECT with pharmacological agents, including lithium, and use of ECT as a maintenance strategy have enhanced our understanding of how and when to utilize this intervention in mania. In this comprehensive review, the authors summarize the evidence regarding the efficacy and safety of ECT in mania, including related syndromes, such as delirious mania and mixed affective states. The impact of technical parameters, particularly the choice of treatment frequency, electrode placements, and pulse width, are discussed in the light of recent evidence.

Amyloid-ß, Tau, and 18F-Fluorodeoxyglucose Positron Emission Tomography in Posttraumatic Stress Disorder.

BACKGROUND: Epidemiological studies suggest a relationship between posttraumatic stress disorder (PTSD) and dementia. OBJECTIVE: This study assessed whether Alzheimer's disease (AD) imaging biomarkers were elevated in Vietnam veterans with PTSD. METHODS: The study compared cognition, amyloid-ß, tau, regional brain metabolism and volumes, and the effect of APOE in 83 veterans with and without PTSD defined by the Clinician-Administered PTSD Scale. RESULTS: The PTSD group had significantly lower education, predicted premorbid IQ, total intracranial volume, and Montreal Cognitive Assessment score compared with the controls. There was no difference between the two groups in the imaging or genetic biomarkers for AD. CONCLUSION: Our findings do not support an association between AD pathology and PTSD of up to 50 years duration. Measures to assess cognitive reserve, a factor that may delay the onset of dementia, were lower in the PTSD group compared with the controls and this may account for the previously observed higher incidence of dementia with PTSD.

Family Presence During Electroconvulsive Therapy.

BACKGROUND: The practice of electroconvulsive therapy (ECT) is often hampered by stigma and myths prevailing among patients and families. Family attendance at ECT has not been systematically studied. METHODS: From January 2017 to May 2018, 69 consecutive patients were approached for family attendance at ECT. The inclusion criteria for entry to the ECT suite were consent from families and patients, age older than 18 years, and 1 family member at a time. After watching ECT, family members completed a multiple-choice questionnaire regarding their experience. RESULTS: Twenty-one family members watched ECT. A majority viewed the idea of attendance at ECT as reassuring, and a few indicated that it was anxiety provoking. Five participants (24%) felt distressed while watching the procedure, whereas 16 family members rated their experience as comfortable or rewarding (76%). In terms of the outcome, a clear majority have responded that watching the procedure alleviated their fears of ECT or provided transformative knowledge, whereas others felt no change in their attitude toward ECT (71% vs 29%). Most of the participants recommended watching ECT to other family members, whereas a minority was uncertain about their opinion (62% vs 38%). There were no adverse effects, premature exit from the ECT suite, interferences with treatment, or litigations. CONCLUSIONS: A clear majority of families viewed their attendance at ECT as a beneficial experience. Family presence during ECT may have the potential to promulgate its practice by reducing stigma and misconceptions.

Risk of Alzheimer's Disease in Obstructive Sleep Apnea Syndrome: Amyloid-ß and Tau Imaging.

BACKGROUND: An association between obstructive sleep apnea (OSA) and Alzheimer's disease has been suggested but little is known about amyloid-ß and tau deposition in this syndrome. OBJECTIVE: To determine amyloid and tau burden and cognitive function in OSA in comparison with those without a diagnosis of OSA. METHODS: The status of OSA was determined by asking participants about history of polysomnographic diagnosis of OSA and the use of Continuous Positive Airway Pressure (CPAP). A comprehensive neuropsychological battery measured cognitive function. Positron emission tomography (PET) was used to measure standardized uptake value ratio (SUVR) of 18F-florbetaben and 18F-AV1451, to quantify amyloid and tau burden. RESULTS: 119 male Vietnam veterans completed assessment. Impairment in visual attention and processing speed and increased body mass index (BMI) were seen in subjects with OSA compared with those without a diagnosis OSA. The cortical uptake of 18F-florbetaben was higher in the OSA group than in the control group (SUVR: 1.35±0.21 versus 1.27±0.16, p = 0.04). There were more apolipoprotein E ɛ4 allele (APOE ɛ4) carriers in the OSA group than in the control group. In multilinear regression analysis, the significance of OSA in predicting 18F-florbetaben uptake remained independent of age and vascular risk factors but not when BMI or APOE ɛ4 was adjusted. The reported use of CPAP (n = 14) had no effect on cognitive or amyloid PET findings. There was no significant difference in 18F-AV1451 uptake between the two groups. CONCLUSIONS: Obstructive sleep apnea is associated with Alzheimer's disease pathology, but this relationship is moderated by APOE ɛ4 and BMI.

Electroconvulsive therapy in the continuation and maintenance treatment of depression: Systematic review and meta-analyses.

OBJECTIVE: Acute course of electroconvulsive therapy is effective in inducing remission from depression, but recurrence rate is unacceptably high following termination of electroconvulsive therapy despite continued pharmacotherapy. Continuation electroconvulsive therapy and maintenance electroconvulsive therapy have been studied for their efficacy in preventing relapse and recurrence of depression. The purpose of this meta-analysis was to examine the efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy in preventing relapse and recurrence of depression in comparison to antidepressant pharmacotherapy alone. METHODS: We searched MEDLINE, Embase, PsycINFO, clinicaltrials.gov and Cochrane register of controlled trials from the database inception to December 2016 without restriction on language or publication status for randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. Two independent Cochrane reviewers extracted the data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. The risk of bias was assessed using four domains of the Cochrane Collaboration Risk of Bias Tool. Outcomes were pooled using random effect model. The primary outcome was relapse or recurrence of depression. RESULTS: Five studies involving 436 patients were included in the meta-analysis. Analysis of the pooled data showed that continuation electroconvulsive therapy and maintenance electroconvulsive therapy, both with pharmacotherapy, were associated with significantly fewer relapses and recurrences than pharmacotherapy alone at 6 months and 1 year after a successful acute course of electroconvulsive therapy (risk ratio = 0.64, 95% confidence interval = [0.41, 0.98], p = 0.04, risk ratio = 0.46, 95% confidence interval = [0.21, 0.98], p = 0.05, respectively). There was insufficient data to perform a meta-analysis of stand-alone continuation electroconvulsive therapy or maintenance electroconvulsive therapy beyond 1 year. CONCLUSION: There are only a few randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. The preliminary and limited evidence suggests the modest efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy with concomitant pharmacotherapy in preventing relapse and recurrence of depressive episodes for 1 year after the remission of index episode with the acute course of electroconvulsive therapy.

Ultrabrief Electroconvulsive Therapy for Mania: Data From 11 Acute Treatment Courses.

Electroconvulsive therapy (ECT) is an effective treatment of mania. Ultrabrief ECT is a novel modality that is associated with fewer cognitive adverse effects than the standard pulse width brief pulse ECT. It has been well studied in depression. However, its use in mania is not yet known. Following a retrospective chart view, we report a small sample of patients who had Right Unilateral Ultrabrief ECT (RUB-ECT) for mania. Eleven RUB-ECTs were identified for 9 patients; 72.8% remission rate was observed with RUB-ECT. Two patients required switch into bitemporal ECT in view of minimal clinical response and 1 patient to right unilateral brief pulse ECT because of poor seizure parameters. All patients achieved remission eventually. The possible mechanisms of ECT in mania and clinical implications of ultrabrief ECT are discussed.

Retrospective comparison of effectiveness of right unilateral ultra-brief pulse with brief pulse ECT in older adults (over 65) with depression.

BACKGROUND: To compare response, remission and switch (to other pulse width and/or electrode placement) rates and number of treatments between groups receiving right unilateral ultra-brief (RUL-UB), Bitemporal brief (BT), Bifrontal Brief (BF) and Right unilateral brief (RUL-B). METHOD: Data was collected from case notes in three centers. There were 133 in total, grouped as RUL-UB (50), BT (43), BF (23), RUL-B (17). Two of the three centers had a preferred electrode placement and pulse width. RESULTS: Apart from age, the groups did not differ significantly on sex distribution, proportion of bipolar depression and psychotic symptoms. 56% of patients in RUL-UB switched compared to 12.5% in RUL-B, 4.9% in BT and none in BF (p value < 0.0001). When we considered patients who switched as treatment failures, remission rates were significantly different (p value < 0.0001) 40% in RUL-UB, 81.3% in RUL-B, 73.9% in BF and 78.0% in BT. Mean number of treatments in each group was significantly different (p value < 0.0001); 12.02 in RUL-UB, 10.2 in RUL-B, 7 in BF and 7.5 in BT. Post-hoc analysis indicated that RUL-UB differed significantly from BT and BF. Final response and remission rates including patients who switched were 98% and 82% in RUL-UB, 100% and 93.8% in RUL-B, 100% and 73.9% in BF and 97.7% and 83.7% in BT. CONCLUSION: Majority commencing RUL-UB switched and received 4-5 more treatments compared to bilateral placements. RUL-UB ECT appears less effective and might not be appropriate as first line for all older adults as some patients at higher anaesthetic risk would benefit from having reduced number of treatments.

Insomnia in Cancer--Associations and Implications.

BACKGROUND: Insomnia is a common condition in cancer patients. In spite of the high prevalence its associations have not been well studied. Existing data suggests that insomnia is related to depression and pain. However, the impact of ongoing chemotherapy on sleep is not investigated. AIM: To study the relationship between insomnia and chemotherapy after analysing confounding variables. MATERIALS AND METHODS: Consecutive patients who visited New England Oncology Clinic in Tamworth were recruited. Insomnia was assessed with the Bergen insomnia scale. The Montgomery Asberg Depression rating scale was used to measure depression. Pain was assessed with the Brief Pain inventory. Chronic medical conditions, type of cancer, side effects to chemotherapy, role of steroids and other drugs were studied as confounders. RESULTS: A total of 56 patients participated in the study. Age ranged from 33 to 83 years (mean: 63.6, SD=10.97). There were 29 men and 27 women. 42 patients received at least one form of chemotherapy and 15 were receiving radiotherapy at the time of assessment. Mean insomnia score was significantly higher in those receiving chemotherapy than in those without chemotherapy (8.92 vs 17.2, two tailed p=0.005, 95% CI=2.63-13.71). There was no significant variation in insomnia scores in terms of chronic medical condition, type of cancer, psychiatric history, use of steroids or adverse effects of chemotherapy. However, total insomnia score was correlated with depression rating score (Pearson correlation, r=0.39, p=0.003) and magnitude of pain (r=0.37, p=0.006). On regression analysis only pain was found to be predictive of insomnia. CONCLUSIONS: Insomnia in patients with cancer is found to be associated with concurrent chemotherapy and correlated with degree of depression and pain. Identifying factors related to insomnia in cancer population has implications in its management and patient education.

Management impact of FDG-PET in dementia: results from a tertiary center memory clinic.

BACKGROUND: 2-[18F]fluoro-2-Deoxy-D-glucose (FDG) positron emission tomography (PET) may assist the diagnosis of dementia but it is an expensive investigation. OBJECTIVE: To obtain management impact data for FDG-PET in dementia. METHODS: This was a prospective study of 194 consecutive patients referred from a memory clinic for FDG-PET at the discretion of the dementia specialists. Diagnosis and management plans formulated at a multidisciplinary patient review meeting were compared before and after the release of PET findings. RESULTS: FDG-PET had moderate to high impact on the diagnosis and management in 85 (44%) participants. Diagnosis changed from probable neurodegenerative disease in 27 patients to a non-degenerative diagnosis and vice versa in 12 patients. PET changed the type of dementia in another 29 (15%) participants and prescription of cholinesterase inhibitors in 33 patients (17%). Number of uncertain diagnoses reduced from 58 to 35 (p < 0.001, χ2 = 15.12), differential diagnoses reduced from 127 to 55 (p = 0.003) and very probable diagnoses increased from 5 to 42 (p ≤ 0.001, χ2 = 1.01). Mini-Mental State Examination score was higher in those where PET had high diagnostic impact (26.3 ± 3.1 versus 23.9 ± 5.1, p ≤ 0.05). The degree of impact correlated with the pre-scan level of diagnostic uncertainty (ρ = -0.258, p < 0.001). DISCUSSION: The management impact was higher in those with greater diagnostic uncertainty and in those with less severe cognitive impairment. The findings suggest that FDG-PET is a useful adjunct for the management of suspected dementing disorders in appropriately selected patients.

Maintenance electroconvulsive therapy up to 12 years.

BACKGROUND: Maintenance electroconvulsive therapy (m-ECT) is effective in preventing recurrences of depressive episodes. There is little information on long-term m-ECT extending over several years and its impact on cognitive functions. This study was an attempt to determine the efficacy and side effects of long-term m-ECT. METHOD: Depressive episodes and admissions before m-ECT for a period equal to the duration of m-ECT and during m-ECT were compared using medical records. Cognitive functions assessed by Mini-Mental State Examination (MMSE) before and after m-ECT were compared along with the review of Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG). RESULTS: 17 patients had m-ECT that extended from 6 to 153 months (mean 39, SD=44.46). The average number of episodes before and during m-ECT was 2.47 (SD=2.23) and 0.88 (SD=1.31) respectively (Wilcoxon ranked test Z=3.06, r=0.55, two-tailed p=0.002). Average number of admissions dropped from 2.05 (SD=1.88) to 0.23 (SD=0.43) during m-ECT (Z=3.471, r=0.71, p=0.001). The average time to recurrence was 24.24 months (SD=25.20) with longest depression free survival of 105 months. There was no significant difference in MMSE score before and after the commencement m-ECT or progressive deterioration in NUCOG score. LIMITATIONS: This study was limited by retrospective nature of data collection, small sample size, confounding effects of antidepressants along with m-ECT and absence of a highly sensitive cognitive screening tool that can capture all types of cognitive impairments following m-ECT. CONCLUSIONS: In a naturalistic setting the efficacy of m-ECT may extend over several years while cognitive functions remain largely unaffected.

Angioedema and maculopapular eruptions associated with carbamazepine administration.

Cutaneous rashes and eruptions can be caused by many medications, including carbamazepine. The presentation can be varied depending on severity. Cutaneous eruptions occur in 3% of individuals administered carbamazepine. Angioedema, a rare side effect of carbamazepine, involves vascular leakage in dermis and subcutis mediated by immunoglobulin E and/or bradykinins. Angioedema is more common in females and in the third decade of life. We report the case of a 27-year-old Indian woman who developed maculopapular rash and angioedema secondary to carbamazepine administration. The patient responded successfully to withdrawal of the drug and treatment with antihistamines. Due to the potentially life-threatening complications of this condition and the increasing use of anticonvulsants in the treatment of mood disorders, psychiatrists must be aware of the diagnosis and treatment of this condition.