Low-level lithium in drinking water and subsequent risk of dementia: Cohort study.

BACKGROUND: Lithium, a mood stabilizer, is known to exhibit neuroprotective effects in animal models and may have anti-dementia effects. AIMS: We used data from Scottish Mental Survey 1932, a population-based cohort study, to investigate the association between lithium in drinking water and dementia rate in humans. METHOD: Lithium levels in drinking water from 285 sampling sites across Scotland dating from 2014 were obtained from the sole public water provider (Scottish Water). Dementia and non dementia cases were identified from cohort data by electronic health records until 2012, and linked to postcode. RESULTS: The mean lithium level at all sampling sites was 1.45 µg/L (SD 1.83, range 0.5-18.2) and was 1.26 (SD 0.63, range 0.55-9.19) for sites matched to participant data. Of 37,597 study members, 3605 developed dementia until June 2012. Lithium levels were positively associated with the risk of dementia in women (highest in second quartile, HR 1.17, 95%CI 1.04-1.32), but there was no relationship in men (highest in second quartile, HR 0.95, 95% CI 0.81-1.12). The pattern of association was explored further by decile, and in females there was an association between lithium level and increased dementia risk compared to the lowest decile (0.55-0.68 µg/L) in all deciles except the highest, corresponding with lithium levels 0.68-2.1 µg/L. CONCLUSIONS: Lithium levels in drinking water are very low across Scotland which limited detection of potential effect. Our results do not support an association between extremely low levels of lithium and later dementia risk. We found a trend to increased risk in females at lithium levels below but not above 2.1 µg/L.

Invited commentary on Lithium treatment and risk for dementia in adults with bipolar disorder.

Alzheimer's disease clinical trials are failing at an alarming rate, highlighting the desperate need for novel thinking to combat this escalating health crisis. A recent large-scale population study indicates that lithium treatment reduces dementia development, supporting preclinical mechanistic evidence that this commonly used agent might be clinically valuable in dementia.

Anticonvulsant Mechanisms of Electroconvulsive Therapy and Relation to Therapeutic Efficacy.

BACKGROUND: Electroconvulsive therapy (ECT) is held to confer anticonvulsant effects, although the role of rise in seizure threshold upon clinical effect is uncertain. This study investigated the relationship in a large, consecutive, retrospective sample of patients receiving ECT in Aberdeen. We have tested the hypotheses of previous authors to further examine the relationship between seizure and therapeutic effect as well as discuss the potential underlying neurobiological mechanisms. METHODS: All patients receiving ECT at the Royal Cornhill Hospital between 2000 and the end of 2008 were identified from the Scottish ECT Accreditation Network. Electroconvulsive therapy was administered twice weekly with a bifrontotemporal electrode placement using routine dosage schedules. Data were gathered from the Scottish ECT Accreditation Network and case notes regarding ECT course and clinical effect. RESULTS: The seizure threshold increased in 219 (94.4%) patients, stayed the same in 13 (5.6%) patients, and decreased in 0 patient (n = 232). No significant relationship was present between change in seizure threshold and change in Montgomery-Asberg Depression Rating Scale score (P = 0.39; Kendall τ b r = 0.047; n = 182), although responders did display greater increase in seizure threshold than nonresponders. CONCLUSIONS: Electroconvulsive therapy confers anticonvulsant effects in a consecutive sample of real-life patients. Neither initial seizure threshold nor magnitude of seizure threshold increase is a predictor of clinical response to ECT. A rise in seizure threshold is not essential for therapeutic effect but may represent an important marker of underlying neuronal state. The evidence reviewed in this article supports a link between neuroplastic effects of ECT and the evidenced rise in seizure threshold.

Homocysteine, antioxidant micronutrients and late onset dementia.

PURPOSE: To distinguish between contributions to dementia made by homocysteine, folate, B12 and antioxidant micronutrients. METHODS: This is a follow-up study of a sample reported in 2002. Homocysteine was measured at baseline in 201 individuals born in 1921 and without dementia at age 77 years and followed up to age 88 years. Baseline macro- and micronutrient status was estimated from BMI, the MONICA food frequency questionnaire, plasma folate, B12 and, in a subgroup (N = 173), plasma antioxidant micronutrients. Time to dementia onset during follow-up was compared between participants grouped by homocysteine concentration using Cox regression. Model 1 adjusted for age, sex, childhood IQ, education, socioeconomic deprivation, presence of heart disease, hypertension, plasma folate and B12. In model 2 plasma, antioxidants were added to these covariables. RESULTS: During a mean follow-up of about 5 years, there were 39 incident dementia cases among 201 participants. In model 1, being in the highest homocysteine group (>14 µmol/L) was associated with a 234 % increased risk (HR 3.34, 95 % CI 1.16-9.57) of any dementia. After inclusion of plasma antioxidants in model 2, there were 32 incident dementia cases from a subsample (N = 173). Homocysteine >14 µmol was associated with a 272 % increased dementia risk (HR = 3.72, 95 % CI 1.06-13.08). CONCLUSIONS: High homocysteine increases the risk of dementia. The association between tHcy and dementia is independent of plasma folate, B12 and antioxidant micronutrient status.

Anticholinergic drugs in late life: adverse effects on cognition but not on progress to dementia.

Impaired cognitive function associated with use of anticholinergic drugs may be partly attributed to underlying physical illness and exposure to factors that increase the risk of some physical disorders such as low socioeconomic status (SES) and less education. To estimate the extent of cognitive impairment and risk of progress to dementia associated with anticholinergic drug use and to estimate confounding by gender, APOE, family history of dementia, lower SES, less education, and lower childhood mental ability, we recruited 281 volunteers at age 77-78 without overt dementia who had taken part in the Scottish Mental Survey of 1932. Clinical histories, use of medications, self reported frequency of emotional symptoms and standardized tests of cognitive function were obtained. With and without adjustment for age and childhood IQ, there were significant between-group differences in tests of non-verbal reasoning and spatial ability. During 10 year follow-up, progress to overt dementia was not associated with anticholinergic drugs use on recruitment but female gender and a history of dementia in parent or sibling were associated with dementia. We concluded that anticholinergic drug use in this narrow age range sample was linked to cognitive impairment but not to subsequent dementia.

Experience of an Inter-regional Research Symposium for Higher Psychiatric Trainees in Scotland.

OBJECTIVES: We present our experience of an annual research symposium for psychiatric trainees in Scotland. This paper aimed to consider trainees' involvement in research by examining firstly rates of publication and secondly the views of trainees. METHODS: A list of all presentations to the Senior Trainees' Annual Research Symposium (STARS) meetings 2007-2009 was compiled and a detailed search made of major research databases. A questionnaire survey examined the views of attendees at the 2009 meeting. RESULTS: Fifty percent of presented work achieved publication. Feedback from symposia attendees was almost universally positive. CONCLUSIONS: At a time of debate on the value of research sessions as part of higher training and a recent reduction in time allocated to research in the UK, we report on a thriving annual meeting. Research symposia for higher trainees were valued by participants and may be one useful means of encouraging trainee research.