Editorial. : The journal at age 5.

The journal () was conceived to serve at the border zone between the fields of cognition, brain vascular function, cerebrovascular disease and neurodegeneration. An umbrella term often used for this spectrum of disorders or conditions is Vascular contributions to Cognitive Impairment and Dementia (VCID). The journal was launched in 2020.

The promise of molecular science in brain health. What breakthroughs are anticipated in the next 20 years?

Brain health means optimal physiological brain function across the normal life-course. It encompasses not only healthy brain aging but also brain diseases, their diagnosis and treatment. In all these areas, molecular science has advanced our understanding.

Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage.

Background: Genetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure.

Methods: Vascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH.

Introduction to the special issue on brain health.

None.

What will it take to achieve brain health globally?

Brain health initiatives and programs are gaining traction worldwide. Some are clinically based, others research based, and some are a combination of clinical and research action plans. Achievement of global brain health is a challenging endeavor with prerequisites including but not limited to multidisciplinary and multisectoral approaches, strengthening of neurologic policies at local and regional levels, global advocacy, leadership and collaboration amongst stakeholders, development of technical and guidance documents, and strengthening and interpretation of the relevant evidence.

Racial Disparities in Pelvic Floor Disorders.

Objective: To investigate the impact of racial disparities and socioeconomic status on pelvic floor disorder (PFD) care.

Background: Racial disparities in colorectal PFD remain uninvestigated, despite prior research in urogynecology.

Methods: This retrospective study was conducted at Guy's and St.

Is an uncomplicated postoperative recovery following total pelvic exenteration a more important prognostic factor than achieving R0 in the first 2 years?

Aim: Total pelvic exenteration (TPE) can achieve an R0 resection in locally advanced and recurrent rectal cancer (LARC and RRC) and remains the only curative option. The resultant high morbidity creates prolonged complex recoveries, rendering patients unfit for adjuvant chemotherapy. This study aims to evaluate the impact of this on overall survival (OS) and disease-free survival (DFS) as it has not been studied previously.

Cerebral Small Vessel Disease, Hypertension, and Vascular Contributions to Cognitive Impairment and Dementia.

Hypertension-associated cerebral small vessel disease is a common finding in older people. Strongly associated with age and hypertension, small vessel disease is found at autopsy in over 50% of people aged ≥65 years, with a spectrum of clinical manifestations. It is the main cause of lacunar stroke and a major source of vascular contributions to cognitive impairment and dementia.

A multi-disciplinary commentary on preclinical research to investigate vascular contributions to dementia.

Although dementia research has been dominated by Alzheimer's disease (AD), most dementia in older people is now recognised to be due to mixed pathologies, usually combining vascular and AD brain pathology. Vascular cognitive impairment (VCI), which encompasses vascular dementia (VaD) is the second most common type of dementia. Models of VCI have been delayed by limited understanding of the underlying aetiology and pathogenesis.

Differences in quality of life of patients undergoing total pelvic exenteration compared with standard rectal cancer surgery: a scoping review.

Aim: Rectal cancer is often treated surgically with an anterior resection (AR) or abdominoperineal excision (APE). However, for patients with locally advanced disease or local recurrence total pelvic exenteration (TPE) surgery can be performed. The magnitude of surgery varies, and little research has been done to consider how quality of life (QoL) may vary according to the extent of surgery.

Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial.

Unlabelled: Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment).

PDE5 inhibitor drugs for use in dementia.

Unlabelled: Alzheimer's disease and related dementias (ADRD) remain a major health-care challenge with few licensed medications. Repurposing existing drugs may afford prevention and treatment. Phosphodiesterase-5 (PDE5) is widely expressed in vascular myocytes, neurons, and glia.

One-health approach to canine cognitive decline: Dogs Overcoming Geriatric Memory and Aging Initiative for early detection of cognitive decline.

Treatment options for human dementia remain limited, and additional research is needed to develop and validate translational models. Canine cognitive decline (CCD) is common in older dogs and a major source of morbidity. The decline includes physiological and behavioral changes comparable to those in humans diagnosed with dementia.

Pelvic floor imaging in asymptomatic subjects.

Aim: The aim of this work was to determine the range of normal imaging features during total pelvic floor ultrasound (TPFUS) (transperineal, transvaginal, endovaginal and endoanal) and defaecation MRI (dMRI).

Method: Twenty asymptomatic female volunteers (mean age 36.5 years) were prospectively investigated with dMRI and TPFUS.

Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective.

A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND.

Intraoperative bowel perfusion assessment methods and their effects on anastomotic leak rates: meta-analysis.

Background: Anastomotic leak is one of the most feared complications of colorectal surgery, and probably linked to poor blood supply to the anastomotic site. Several technologies have been described for intraoperative assessment of bowel perfusion. This systematic review and meta-analysis aimed to evaluate the most frequently used bowel perfusion assessment modalities in elective colorectal procedures, and to assess their associated risk of anastomotic leak.

Multimodal prehabilitation service for patients with colorectal cancer: the challenges of implementation.

Prehabilitation has been shown to improve outcomes for patients undergoing major surgery; benefits include reductions in length of hospital stay and postoperative complications. Multimodal prehabilitation programmes lead to improved patient engagement and experience. This report describes implementation of a personalised multimodal prehabilitation programme for patients awaiting colorectal cancer surgery.

Preoperative predictors of success after transvaginal rectocoele repair.

Purpose: Determine predictors of success for transvaginal rectocoele repair (TVRR). Primary aim is to establish predictors of successful treatment analysing patients' characteristics, baseline symptoms, pelvic floor test results and pre-operative conservative treatment.

Methods: Retrospective single institution study in a tertiary referral centre for pelvic floor disorders.

ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 mutations. Typical CADASIL is characterised by subcortical ischemic strokes due to severe arteriopathy and fibrotic thickening of small arteries. Arteriolar vascular smooth muscle cells (VSMCs) are the key target in CADASIL, but the potential mechanisms involved in their degeneration are still unclear.

Pelvic floor investigations for anal incontinence: Are they useful to predict outcomes from conservative treatment?

Aims: There are several options for treating anal incontinence (AI), with limited success rate in long-term follow-up. Patients' selection is important to avoid unnecessary investigations and therapies. The aim of this review is to assess the utility of pelvic floor investigations to predict success from conservative treatment in AI.

The association between levator plate integrity and pelvic floor defaecatory dysfunction.

Aims: Levator ani deficiency has been implicated in anterior pelvic floor pathology but its association with pelvic floor defaecatory dysfunction is less clear. The aim was to examine the relationship of levator ani deficiency with anatomical abnormalities (rectocoele, intussusception, enterocoele, perineal descent) and patient symptoms (bowel, vagina) in patients with pelvic floor defaecatory dysfunction.

Methods: The prospective observational case series of 223 women presenting to a tertiary colorectal pelvic floor unit with defaecatory dysfunction.

Monkeypox-associated proctitis and rectal wall perforation.

Monkeypox is a viral zoonotic infection which has rapidly increased in incidence and spread globally since May 2022. There have been reports of rectal complications of monkeypox but so far these are not well not understood. Here, we describe a case of rectal pain in HIV-positive man with confirmed monkeypox.

What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders?

•Controversial registration of aducanumab for Alzheimer's Disease•Aducanumab is the subject of post-licensing observational studies aiming to follow the effects of the drug•Given the high prevalence of cerebrovascular pathology it is important that these studies do not ignore vascular cognitive disorders•The studies may give detailed phenotyping data that may lead to knowledge of targets for treatments of patients with vascular cognitive disorders.