Associations between psychological intervention for anxiety disorders and risk of dementia: a prospective cohort study using national health-care records data in England.

BACKGROUND: Meta-analyses support an association between anxiety in older adulthood and dementia. The aim of this study was to use routinely collected health data to test whether treatment of anxiety disorders through psychological intervention is associated with a lower incidence of dementia. METHODS: In this prospective cohort study, data from nationally provided psychological therapy services in England termed Improving Access to Psychological Therapies from 2012 to 2019 were linked to medical records, including dementia diagnoses as defined by the tenth edition of the International Classification of Diseases, up to 8 follow-up years later. Inclusion criteria were as follows: (1) patients who were aged 65 years and older; (2) patients with a probable anxiety disorder; and (3) those with no previous or current diagnosis of dementia. Cox proportional hazards models were constructed to test whether reliable improvement in anxiety following psychological intervention was associated with future dementia incidence. The primary outcome was all-cause dementia and cases were identified using ICD-10 dementia codes from Hospital Episode Statistics, Mental Health Services Dataset, and mortality data. For main analyses, hazards ratios (HRs) are presented. FINDINGS: Data from 128 077 people aged 65 years and older attending a nationally provided psychological intervention service in England were linked to medical records. 88 019 (69·0%) of 127 064 participants with available gender data were women and 39 585 (31·0%) were men. 111 225 (95·9%) of 115 989 with available ethnicity data were of White ethnicity. The mean age of the sample was 71·55 years (SD 5·69). Fully adjusted models included data from 111 958 people after 16 119 were excluded due to missing data on key variables or covariates. 4510 (4·0%) of 111 958 participants had a dementia diagnosis. The remaining 107 448 (96·0%) were censored either at date of death or when the final follow-up period available for analyses was reached. People who showed reliable improvement in anxiety had lower rates of later dementia diagnosis (3·9%) than those who did not show reliable improvement (5·1%). Reliable improvement in anxiety following psychological intervention was associated with reduced incidence of all-cause dementia (HR 0·83 [95% CI 0·78-0·88]), Alzheimer's disease (HR 0·85 [0·77-0·94]), and vascular dementia (HR 0·80 [0·71-0·90]). Effects did not differ depending on anxiety disorder diagnosis. INTERPRETATION: Results showed that reliable improvement in anxiety from psychological therapy was associated with reduced incidence of future dementia. There are multiple plausible explanations for this finding and further research is needed to distinguish between these possibilities. Missing data in the sample limit reliability of findings. FUNDING: Alzheimer's Society, Medical Research Council, Wellcome Trust, and UCLH National Institute for Health and Care Research Biomedical Research Centre.

Associations between psychological therapy outcomes for depression and incidence of dementia.

BACKGROUND: Depression is an important, potentially modifiable dementia risk factor. However, it is not known whether effective treatment of depression through psychological therapies is associated with reduced dementia incidence. The aim of this study was to investigate associations between reduction in depressive symptoms following psychological therapy and the subsequent incidence of dementia. METHODS: National psychological therapy data were linked with hospital records of dementia diagnosis for 119808 people aged 65+. Participants received a course of psychological therapy treatment in Improving Access to Psychological Therapies (IAPT) services between 2012 and 2019. Cox proportional hazards models were run to test associations between improvement in depression following psychological therapy and incidence of dementia diagnosis up to eight years later. RESULTS: Improvements in depression following treatment were associated with reduced rates of dementia diagnosis up to 8 years later (HR = 0.88, 95% CI 0.83-0.94), after adjustment for key covariates. Strongest effects were observed for vascular dementia (HR = 0.86, 95% CI 0.77-0.97) compared with Alzheimer's disease (HR = 0.91, 95% CI 0.83-1.00). CONCLUSIONS: Reliable improvement in depression across psychological therapy was associated with reduced incidence of future dementia. Results are consistent with at least two possibilities. Firstly, psychological interventions to improve symptoms of depression may have the potential to contribute to dementia risk reduction efforts. Secondly, psychological therapies may be less effective in people with underlying dementia pathology or they may be more likely to drop out of therapy (reverse causality). Tackling the under-representation of older people in psychological therapies and optimizing therapy outcomes is an important goal for future research.

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: A British birth cohort study.

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study (NCDS), a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44-45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time.

Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR.

Adeno-associated virus (AAV) vectors are preeminent in emerging clinical gene therapies. Generalizing beyond the most tractable genetic diseases will require modulation of cell specificity and immune neutralization. Interactions of AAV with its cellular receptor, AAVR, are key to understanding cell-entry and trafficking with the rigor needed to engineer tissue-specific vectors. Cryo-electron tomography shows ordered binding of part of the flexible receptor to the viral surface, with distal domains in multiple conformations. Regions of the virus and receptor in close physical proximity can be identified by cross-linking/mass spectrometry. Cryo-electron microscopy with a two-domain receptor fragment reveals the interactions at 2.4 Å resolution. AAVR binds between AAV's spikes on a plateau that is conserved, except in one clade whose structure is AAVR-incompatible. AAVR's footprint overlaps the epitopes of several neutralizing antibodies, prompting a re-evaluation of neutralization mechanisms. The structure provides a roadmap for experimental probing and manipulation of viral-receptor interactions.

Towards evidence-based emergency medicine: Best BETs from the Manchester Royal Infirmary. BET 1: Local anaesthetics in intraosseous access.

A short-cut review was carried out to establish whether flushing an intraosseous needle with local anaesthetic or saline is more effective at reducing the pain injecting drugs or fluid via this route. Two studies were relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are shown in table 1. The clinical bottom line is that injecting lidocaine both before and after flushing an intraosseous needle is an effective method of reducing the pain of fluid infusion via this route.