Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

Background: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis.

Results: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.

A 2025 update on treatment strategies for the Alzheimer's disease spectrum.

Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder with a continuum of stages ranging from preclinical/asymptomatic phase to severe dementia. Over the past decades, significant advances in diagnostic biomarkers and disease-modifying therapies have reshaped the treatment landscape. This review provides a comprehensive overview of the current treatment paradigm for AD in 2025, incorporating the latest developments in pharmacological and non-pharmacological interventions.

From Acute Confusion to Chronic Decline: The Cognitive Impact of Delirium in Older Adults.

Delirium is prevalent in healthcare settings, leaving susceptible older adults at risk for persistent cognitive impairment, prolonged care needs, morbidity, and mortality. In older adult patients, delirium often arises from acute medical illnesses, infections, medications, and comorbidities, with age and underlying dementia increasing susceptibility. Its complex pathophysiology involves systemic inflammation, neurotransmitter dysregulation, disrupted brain metabolism, and physiological cycle disturbances.

The Alzheimer's Disease Continuum - A New Diagnostic Approach.

The management of Alzheimer's disease (AD) is in the process of transitioning into a new era, enabled by 50 years of scientific progress elucidating biological and clinical aspects of the AD continuum. Newly FDA-approved disease modifying therapies have driven greater access to amyloid positron emission tomography imaging, and fluid biomarker technology has produced the first blood-based biomarkers for AD that are currently entering the marketplace. Community practitioners are increasingly finding themselves on the front lines of advanced AD biomarker decision-making that was in the very recent past the domain of subspecialty memory center providers.

Cerebello-Parietal Functional Connectivity in Amnestic Mild Cognitive Impairment.

The role of the cerebellum in amnestic mild cognitive impairment (aMCI), typically a prodromal stage of Alzheimer's disease, is not fully understood. We studied the lobule-specific cerebello-cerebral connectivity in 15 cognitively normal and 16 aMCI using resting-state functional MRI. Our analysis revealed weaker connectivity between the cognitive cerebellar lobules and parietal lobe in aMCI.

Comparative safety and cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in nursing homes.

Aim: Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents.

Materials And Methods: Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018.

Cognitive Function Remains Associated With Functional Impairment in Profound Dementia: Alzheimer Disease and Dementia With Lewy Bodies.

Background And Objectives: The Baylor Profound Mental Status Examination (BPMSE) was developed to assess cognitive function in the profound stage of dementia. The Clinical Dementia Rating (CDR) scale has been widely used in measuring functional performance in dementia. We aimed to determine whether cognitive function is related to overall functional impairment in profound dementia.

Estimation of non-monotonic transition rates in a semi-Markov process with covariates adjustments and application to caregivers' stress data.

With the large ongoing number of aged people and Alzheimer's disease (AD) patients worldwide, unpaid caregivers have become the primary sources of their daily caregiving. Alzheimer's family caregivers often suffer from physical and mental morbidities owing to various reasons. The aims of this paper were to develop alternate methods to understand the transition properties, the dynamic change, and the long-run behavior of AD caregivers' stress levels, by assuming their transition to the next level only depends on the duration of the current stress level.

Ataxias: Hereditary, Acquired, and Reversible Etiologies.

A variety of etiologies can cause cerebellar dysfunction, leading to ataxia symptoms. Therefore, the accurate diagnosis of the cause for cerebellar ataxia can be challenging. A step-wise investigation will reveal underlying causes, including nutritional, toxin, immune-mediated, genetic, and degenerative disorders.

Cerebellar impulsivity-compulsivity assessment scale.

Objective: The cerebellum has been identified as the key brain region that modulates reward processing in animal models. Consistently, we recently found that people with cerebellar ataxia have impulsive and compulsive behaviors (ICBs), the main symptoms related to abnormal reward processing. Due to the lack of a validated scale to quantitatively measure ICBs in cerebellar disorders, we aim to develop and validate a new scale, Cerebellar Impulsivity-Compulsivity Assessment (CIA).

Hypertension differentially impacts cognition in men and women in early midlife.

The current study aimed to understand how sex differences in the timing of hypertension onset contribute to early midlife risk for cognitive decline that may differ by sex and whether sex-dependent advantages in normotensive populations are influenced by the presence of hypertension. One hundred and ninety-five adults aged 45-55 from the New England Family Study underwent neuropsychological testing to assess attention, executive function, and memory. Physician-diagnosed hypertension status was self-reported via questionnaire.

Novel blood test for early biomarkers of preeclampsia and Alzheimer's disease.

A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer's disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates.

Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer's Disease.

Background: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer's disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood.

Objective: We utilized Alzheimer's Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD.

Methods: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal).

Different Cognitive Profiles Are Associated with Progression Rate and Age at Death in Probable Alzheimer's Disease.

Background: Cognitive profiles characterized by primarily language or visuospatial deficits have been documented in individuals meeting diagnostic criteria for probable Alzheimer's disease (AD), but their association with progression rate or overall survival is not well described.

Objective: To compare time from diagnosis to severe disease stage and death in probable AD patients classified into three groups based on neuropsychological test performance: marked verbal impairment (Verb-PI) with relatively preserved visuospatial function, marked visuospatial impairment with preserved verbal function (Vis-PI), and balanced verbal and visuospatial impairments (Bal-PI).

Methods: This prospective cohort study included 540 probable AD patients attending an academic memory clinic who were enrolled from 1995-2013 and followed annually.

Comparative effectiveness of denosumab, teriparatide, and zoledronic acid among frail older adults: a retrospective cohort study.

Unlabelled: The comparative effects of zoledronic acid, denosumab, and teriparatide for preventing hip fractures in frail older adults, especially those in nursing homes, were unknown. We found that denosumab and zoledronic acid may be as effective as teriparatide for hip fracture prevention in nursing home residents.

Introduction: Several non-oral drugs exist for osteoporosis treatment, including zoledronic acid (ZA), denosumab, and teriparatide.

Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper.

Cytokine storm is an acute hyperinflammatory response that may be responsible for critical illness in many conditions including viral infections, cancer, sepsis, and multi-organ failure. The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19. Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate.

Driving Safety of Cognitively-Impaired Drivers Based on Near Collisions in Naturalistic Driving.

Background: Controlled naturalistic driving for examining impacts of cognitive impairment on driving safety is rare.

Objective: Evaluating the safety among drivers with mild cognitive impairment based on near collision incidents using naturalistic driving, and investigating its correlation with cognitive measures.

Methods: Frequency of near collisions of 44 cognitively impaired [Age = 75.

Postoperative Delirium and Postoperative Cognitive Dysfunction: Overlap and Divergence.

Background: Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up.

Nursing Home Residents by Human Immunodeficiency Virus Status: Characteristics, Dementia Diagnoses, and Antipsychotic Use.

Objectives: Given an aging human immunodeficiency virus (HIV) population, we aimed to determine the prevalence of HIV for long-stay residents in US nursing homes (NHs) between 2001 and 2010 and to compare characteristics and diagnoses of HIV-positive (HIV+) and negative (HIV-) residents. Also, for residents with dementia diagnoses, we compared antipsychotic (APS) medication receipt by HIV status.

Design: A cross-sectional comparative study.

Early-Stage Alzheimer's Disease Is Associated with Simultaneous Systemic and Central Nervous System Dysregulation of Insulin-Linked Metabolic Pathways.

Background: Brain insulin resistance is a well-recognized abnormality in Alzheimer's disease (AD) and the likely mediator of impaired glucose utilization that emerges early and progresses with disease severity. Moreover, the rates of mild cognitive impairment (MCI) or AD are significantly greater in people with diabetes mellitus or obesity.

Objective: This study was designed to determine whether systemic and central nervous system (CNS) insulin resistant disease states emerge together and thus may be integrally related.