Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson's disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis).

To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy.

We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, identifying physical multimorbidity in later life and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer's-disease related neuropathology, Lewy body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 encephalopathy) with logistic models.

Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer's disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson's disease, cerebrovascular disease, depression and other psychiatric conditions) were associated with dementia and neuropathological changes.

Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity

Anxiety disorders are a major public health burden with limited treatment options.

We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness.

This study was an a priori-planned long-term follow-up of an investigator-initiated, two-centre trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 μg) or placebo per period. Participants (n = 39) were followed up 1 year after the end-of-study visit to assess symptoms of anxiety, depression and long-term effects of psychedelics using Spielberger's State-Trait Anxiety Inventory–Global (STAI-G), the Beck Depression Inventory (BDI), the Persisting Effects Questionnaire and measures of personality traits using the NEO-Five-Factor Inventory.

Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = −21.6 (−32.7, −10.4), d = 1.04, P < 0.001, for those who received LSD in the first period (94 weeks after the last LSD treatment) and −16.5 (−26.2, −6.8), d = 1.02, P < 0.05, for those who received LSD in the second period (68 weeks after the last LSD treatment)). Similar effects were observed for comorbid depression with change from baseline BDI scores of −8.1 (−13.2, −3.1), d = 0.71, P < 0.01, and −8.9 (−12.9, −4.9), d = 1.21, P < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased (P < 0.0001) and trait extraversion increased (P < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience.

Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.

Common postpartum mental health (PMH) disorders such as depression and anxiety are preventable, but determining individual-level risk is difficult.

To create and internally validate a clinical risk index for common PMH disorders.

Using population-based health administrative data in Ontario, Canada, comprising sociodemographic, clinical and health service variables easily collectible from hospital birth records, we developed and internally validated a predictive model for common PMH disorders and converted the final model into a risk index. We developed the model in 75% of the cohort (n = 152 362), validating it in the remaining 25% (n = 75 772).

The 1-year prevalence of common PMH disorders was 6.0%. Independently associated variables (forming the mnemonic PMH CAREPLAN) that made up the risk index were: (P) prenatal care provider; (M) mental health diagnosis history and medications during pregnancy; (H) psychiatric hospital admissions or emergency department visits; (C) conception type and complications; (A) apprehension of newborn by child services (newborn taken into care); (R) region of maternal origin; (E) extremes of gestational age at birth; (P) primary maternal language; (L) lactation intention; (A) maternal age; (N) number of prenatal visits. In the index (scored 0–39), 1-year common PMH disorder risk ranged from 1.5 to 40.5%. Discrimination (C-statistic) was 0.69 in development and validation samples; the 95% confidence interval of expected risk encompassed observed risk for all scores in development and validation samples, indicating adequate risk index calibration.

Individual-level risk of developing a common postpartum mental health disorder can be estimated with data feasibly collectable from birth records. Next steps are external validation and evaluation of various cut-off scores for their utility in guiding postpartum individuals to interventions that reduce their risk of illness.