Background and Aims

A decline in cognitive function, with a spectrum ranging from mild cognitive impairment to dementia (CI-D), is common in patients with chronic kidney diseases (CKD), rendering them frailer. Whether the coexistence of CKD and CI-D increases the health risk profile remains unclear. Our work aims to clarify how this association increases adverse outcomes for CKD patients (stages 3-5).

Method

This retrospective observational cohort study was conducted on CKD patients (stages 3-5) from the Global Collaborative Network (GCN) of the TriNetX research platform between 2004 and 2024. TriNetX provides access to anonymized electronic medical records from over half a million CKD patients in large healthcare organizations (HCOs) across the world.

Merlino, Lino, et al. "# 1490 Long-term health outcomes in non-dialysis dependent chronic kidney disease patients with cognitive impairment or dementia." Nephrology Dialysis Transplantation 39.Supplement_1 (2024): gfae069-0673. 

  Between 25–75% of people with persistent post-acute sequelae of SARS-CoV-2 infection (PASC) experience cognitive difficulties, compromising functional ability, quality of life, and activities of daily living, including work. However, despite this significant morbidity, there is a paucity of interventions for this disorder that have undergone evaluation within a formal trial setting. Therefore, we have developed a cognitive rehabilitation programme, specifically designed to address the cognitive symptoms of PASC, notably impaired attention and processing speed, while also accounting for other PASC symptoms (fatigue, post-exertional malaise) that may aggravate the cognitive impairment. This study protocol outlines a randomised controlled trial (RCT) designed to evaluate the effectiveness of this programme compared to standard clinical care.

Martina Vanova, Aysha Mohamed Rafik Patel, Iona Scott et al. Telehealth-delivered cognitive rehabilitation for people with cognitive impairment as part of the post-COVID syndrome: Protocol for a randomised controlled trial as part of the CICERO (Cognitive Impairment in Long COVID: Phenotyping and Rehabilitation) study, 31 May 2024, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-4490002/v1]

  The year 2024 could mark a turning point in our approach to dementia treatment. For decades, the lack of disease-modifying therapies disincentivised investment in dementia diagnosis and care. This was at odds with the growing importance of dementia in the UK and worldwide as a cause of disability and mortality. At the time of writing, dementia is projected to become the costliest healthcare condition by 2040. 

Koychev I, Harrison J, Malhotra P, Dunne R, Sheehan B. Shifting paradigms in dementia care: navigating new therapies and prevention strategies. The British Journal of Psychiatry. 2024;224(6):187-188. doi:10.1192/bjp.2024.75

   The deficit in cerebral blood flow (CBF) seen in patients with hypertension- induced vascular dementia is increasingly viewed as a therapeutic target for disease- modifying therapy. Progress is limited, however, due to uncertainty surrounding the mech-anisms through which elevated blood pressure reduces CBF. To investigate this, we used the BPH/2 mouse, a polygenic model of hypertension. At 8 mo of age, hypertensive mice exhibited reduced CBF and cognitive impairment, mimicking the human presentation of vascular dementia. Small cerebral resistance arteries that run across the surface of the brain (pial arteries) showed enhanced pressure- induced constriction due to diminished activity of large- conductance Ca2+- activated K+ (BK) channels—key vasodilatory ion channels of cerebral vascular smooth muscle cells. Activation of BK channels by transient intracellular Ca2+ signals from the sarco-plasmic reticulum (SR), termed Ca2+ sparks, leads to hyperpolarization and vaso-dilation. Combining patch- clamp electrophysiology, high- speed confocal imaging, and proximity ligation assays, we demonstrated that this vasodilatory mechanism is uncoupled in hypertensive mice, an effect attributable to physical separation of the plasma membrane from the SR rather than altered properties of BK channels or Ca2+ sparks, which remained intact. This pathogenic mechanism is responsible for the observed increase in constriction and can now be targeted as a possible avenue for restoring healthy CBF in vascular dementia.

    Taylor JL, Walsh KR, Mosneag IE, Danby TGE, Luka N, Chanda B, Schiessl I, Dunne RA, Hill-Eubanks D, Hennig GW, Allan SM, Nelson MT, Greenstein AS, Pritchard HAT. Uncoupling of Ca2+ sparks from BK channels in cerebral arteries underlies hypoperfusion in hypertension-induced vascular dementia. Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2307513120. doi: 10.1073/pnas.2307513120. Epub 2023 Aug 7. PMID: 37549299.

   Personalised Alzheimer’s disease prevention and treatment will rely on APOE genotyping but this well-validated predictor is rarely used in routine care

Preventing or delaying dementia due to Alzheimer’s disease (AD) requires personalised risk reduction plans.1 Obesity is a risk factor for dementia, but the ‘obesity paradox’ suggests that higher mid-life Body Mass Index (BMI) is a risk factor for later dementia, whereas higher BMI seems protective in later life. This is partially explained by the long AD prodrome itself causing weight loss,2 but heterogeneity between studies perhaps implies additional mechanisms.

Dunne R, Coulthard E. Tipping the scales towards routine APOE genotyping. Journal of Neurology, Neurosurgery & Psychiatry 2023;94:669.

   Compassionate Healthcare for Excellence in Nursing: Experiences of Nurses and Healthcare Staff Participating in a Reflective Course on Compassion-Based Care; British Journal of Nursing 2019. Donald G, Wilson I, McCarthy J, Hall I, Crossley B, Adshead P, Shaw V, Dunne R, Dwyer T. Br J Nurs. 2019 Aug 8;28(15):1020-1025. doi: 10.12968/bjon.2019.28.15.1020

     Husain MO, Zehra SS, Umer M, Kiran T, Husain M, Soomro M, Dunne R, Sultan S, Chaudhry IB, Naeem F, Chaudhry N, Husain N. Stigma toward mental and physical illness: attitudes of healthcare professionals, healthcare students and the general public in Pakistan. BJPsych Open. 2020 Aug 3;6(5):e81. doi: 10.1192/bjo.2020.66. PMID: 32741419; PMCID: PMC7453804.

     Iracema Leroi, Charlotte Peel, Rebecca Davenport, Ross Dunne, Louise Ebenezer, Mahesh Gopakumar, Vachagan Krishnaswami, Jane Lumsden, Helen Martin, Jane Price and Wilby Williamson (2020) Blueprint for a Brain Health Clinic to Detect and Manage Early-Stage Cognitive Decline: A Consensus Exercise. J Neurodegener Disord 3(1):54-64.