MetaboHealth, not MetaboAge, was associated with cognitive functioning independent of conventional

risk factors. Individual metabolites affect cognitive functioning differently in men and women, suggesting sex-specific

pathophysiological pathways underlying cognitive functioning.

This systematic review examines and synthesises findings from relevant studies, enhancing understanding of the symptoms and implications of MBI in PD. Nine studies from five separate research institutions were identified. The conceptualisation of MBI varied considerably, affecting the reported prevalence rates of MBI in individuals with early-stage PD. Among PwP, MBI was associated higher education and impaired cognition. Affective dysregulation and impulse control disorders were primary contributors to MBI; abnormal perception was least contributor. This systematic review underscores the specific characteristics and incidence of MBI in early-stage PD. Mood and impulse control disorders are primary concerns associated with MBI. Future longitudinal studies are required to clarify the progression of these symptoms and evaluate MBI’s potential as an indicator for PD-related dementia or increased dependency.

Early DOAC initiation within 4 days after ischaemic stroke associated with atrial fibrillation was non-inferior to delayed initiation for the composite outcome of ischaemic stroke, intracranial haemorrhage, unclassifiable stroke, or systemic embolism at 90 days. Our findings do not support the current common and guideline-supported practice of delaying DOAC initiation after ischaemic stroke with atrial fibrillation.

This is the first Italian guideline that makes evidence-based recommendations on the diagnosis, treatment and care for people with dementia and mild cognitive impairment and their caregivers.

New Thirty-four questions were adopted or adapted from the NICE guideline NG97 and 13 new review questions were added, including 10 on the diagnosis and management of people with mild cognitive impairment.

The Italian guideline also included evidence synthesis and recommendations for new disease-modifying drugs.

Frailty measurement in RCTs is highly variable. Understanding the properties of respective frailty measures and how these relate to frailty as encountered in clinical practice is a priority to ensure that trial findings can inform healthcare delivery for people living with frailty.

Suicide risk was highest on Mondays and increased on New Year’s day in most countries. However, the risk of suicide on weekends and Christmas varied by country and territory. The results of this study can help to better understand the short term variations in suicide risks and define suicide prevention action plans and awareness campaigns.

benefits and harms of SGLT-2 inhibitor therapy for adults with CKD over a five year period, along with contextual factors, and provided the following recommendations:

1. For adults at low risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)

2. For adults at moderate risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)

3. For adults at high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour)

4. For adults at very high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour).

Recommendations are applicable to all adults with CKD, irrespective of type 2 diabetes status.

Almost 40 000 people died alone at home in Japan this year—many unnoticed for months—prompting much concern, and new policy. Megan Tatum reports.

This review summarizes current evidence on recommended treatments for acute pericarditis, its prognosis, and the diagnostic evaluation of individuals with suspected initial or recurrent pericarditis.

Objective: Intrinsic capacity (IC) and frailty are complementary constructs that encapsulate functional capacities of older adults. Although earlier studies suggest the utility of composite IC scores in predicting risk of frailty, key gaps remain with the lack of direct comparative studies between different IC scales and lack of a composite score based on the World Health Organization Integrated Care for Older People (ICOPE) tool.We aimed to compare different IC scales, including an ICOPE-based scale, in their predictive ability for risk of frailty at 2 years in healthy community-dwelling older adults.

Conclusions and Implications: Baseline composite IC score using 2-point per domain scales better predicted risk of frailty at 2 years, predicated on impaired locomotion/vitality and greater number of

impaired domains. For early identification of healthy older adults at risk of frailty, an ICOPE-based scale should be considered, as it is effective and accessible.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS. Brexpiprazole is an oral antipsychotic and is the first approved pharmacologic agent in the United States for the treatment of agitation associated with dementia due to AD.

Its effect is thought to be from its partial serotonin 5-HT1A and dopamine D2 receptor agonist activity and serotonin 5-HT2A receptor antagonism. Brexpiprazole is a maintenance medication,

and it should not be used “as needed” or as a “PRN” treatment for breakthrough agitation.

Brexpiprazole is a major substrate of CYP2D6 and CYP3A4. Dose adjustments may be required for drug interactions or impaired renal or hepatic function. Clinical trials found brexpiprazole 2 to 3 mg/d demonstrated significant improvements in agitation, with brexpiprazole showing an approximate 5-point greater reduction on change in the Cohen-Mansfield Agitation Inventory total score at week 12 from baseline compared with placebo.

Brexpiprazole is generally well tolerated and safe, and common adverse reactions when used for this indication include dizziness, headaches, insomnia, nasopharyngitis, somnolence, and urinary tract infections. Like other antipsychotics used for agitation in AD, brexpiprazole is associated with higher mortality rates compared with placebo. In a long-term care setting, there are several considerations for its use. Benefits include an oral agent that is well tolerated and clinical data showing statistically significant effects on agitation. However, brexpiprazole has not been studied in head-to-head clinical trials against other antipsychotics, and there are differing opinions if the agitation score reductions translate to a clinically meaningful difference. The approval of brexpiprazole signals favorably for upcoming agents for this indication, including escitalopram and dextromethorphan-bupropion.

Both escitalopram and dextromethorphan-bupropion are currently undergoing clinical trials.