Analysis of Long-term Follow-up of a Randomized Clinical Trial With Departures From Assigned Treatments: Estimation of Metformin Effects on Diabetes and Its Complications in the Diabetes Prevention Program Outcomes Study.

The Diabetes Prevention Program (DPP) was a 3-year randomized clinical trial (RCT) with evaluation of lifestyle and metformin interventions compared with placebo for diabetes prevention in high-risk adults. Both interventions significantly reduced diabetes incidence, prompting the long-term Diabetes Prevention Program Outcomes Study (DPPOS) to assess the progression of diabetes and its complications over 22 years. During follow-up, departures from the original metformin or placebo assignment occurred primarily because of development of diabetes that, by protocol, was managed by clinicians outside the study, after participants developed diabetes with HbA1c ≥7.

Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex.

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia.

Assessing the Global Impact of Brain Small Vessel Disease on Cognition: The Multi-Ethnic Study of Atherosclerosis.

Introduction: We aimed to examine the global impact of brain small vessel disease (SVD) on cognitive performance.

Methods: In 892 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), we derived perivascular spaces (PVS), white matter hyperintensities (WMH), microbleeds (MB), and white matter fractional anisotropy (FA) and trace (TR). Cognitive function was assessed with a comprehensive neuropsychological battery.

Protocol for a Randomized Phase II/III Double-Blind Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Extended-Release Metformin in Amnestic Mild Cognitive Impairment: Metformin in Alzheimer Dementia Prevention (MAP).

Background: Metformin has been suggested as a possible strategy for the prevention of Alzheimer disease (AD) and AD related dementias. An early phase II clinical trial of short acting metformin versus placebo showed preliminary evidence of efficacy and safety in slowing cognitive decline among persons with amnestic mild cognitive impairment (aMCI) without diabetes.

Objective: To conduct a phase II/III randomized clinical of extended-release metformin versus placebo in participants with aMCI without diabetes.

Performance of a smell identification test versus the Mini-Mental Status Exam for the detection of dementia and cognitive impairment among persons with cognitive concerns in primary care.

BackgroundOdor identification deficits predict Alzheimer's disease (AD) in epidemiological studies.ObjectiveTo compare the accuracy of a short odor identification test with a short cognitive screening test for the detection of dementia and cognitive impairment in elderly persons with cognitive concerns.MethodsThis was a cross-sectional study of 600 participants 65 years and older, without known mild cognitive impairment (MCI) or dementia, with cognitive concerns, attending primary care practices in New York City.

Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial.

Importance: Type 2 diabetes (T2D) is a risk factor for cognitive impairment. Whether the choice of the second-line glucose-lowering treatment added to metformin or glycemic control affects cognitive performance in T2D of relatively short duration (<10 years) is not known.

Objective: To compare the relative effect of 4 classes of glucose-lowering medications that were randomly added to metformin on cognitive performance and to examine the association of longitudinal glycemic levels with cognitive performance.

Heterogeneous tau deposition patterns in the preclinical stage link to domain-specific cognitive deficits.

Introduction: The spatial heterogeneity of tau deposition is closely linked to clinical variants of Alzheimer's disease (AD). Detecting these patterns in the preclinical stage is challenging, but second-generation tau tracers provide a unique opportunity to do so.

Methods: We used independent component analysis (ICA) and tau positron emission tomography (PET) imaging with the 18F-MK6240 tracer in 590 cognitively healthy adults (mean age 66.

Total and Structural Carotid Artery Stiffness Are Associated With Cognitive Decline and Structural Brain Abnormalities Related to Alzheimer Disease and Alzheimer Disease-Related Dementias Pathology: The Multi-Ethnic Study of Atherosclerosis.

Background: Arterial stiffness is associated with pathological changes underlying Alzheimer disease and related dementias. Total pulse wave velocity can be subdivided into 2 main mechanisms: structural arterial stiffness (S-PWV) due to intrinsic remodeling of the artery wall and load-dependent arterial stiffness due to increased blood pressure.

Methods And Results: In this prospective cohort study, MESA (Multi-Ethnic Study of Atherosclerosis) participants completed B-mode carotid ultrasounds from which carotid total pulse wave velocity was calculated.

Alzheimer Disease Blood Biomarkers and Cognition Among Individuals With Diabetes and Overweight or Obesity.

Importance: Blood-based biomarkers (BBMs) are clinically available to aid in the diagnosis of Alzheimer disease (AD) and AD-related dementias (ADRD), but their association with cognition among older adults with specific chronic conditions has not been examined.

Objective: To longitudinally examine associations between baseline AD and ADRD BBMs and change in BBMs with cognition among participants with type 2 diabetes (T2D) and overweight or obesity.

Design, Setting, And Participants: The Look AHEAD (Action for Health in Diabetes) study was a clinical trial of older adults with T2D and overweight or obesity randomized to a 10-year intensive lifestyle intervention for weight loss or a diabetes support and education condition.

Inter-network functional connectivity increases by beta-amyloid and may facilitate the early stage of tau accumulation.

Alzheimer's disease (AD) is pathologically marked by tau tangles and beta-amyloid (Aβ) plaques. It has been hypothesized that Aβ facilitates spread of tau outside of the medial temporal lobe (MTL), but exact mechanism of this facilitation remains unclear. We aimed to test the hypothesis that abnormal Aβ induces an increase in inter-network functional connectivity, which in turn induces early-stage tau elevation in limbic network.

Long-term impact of Diabetes Prevention Program interventions on walking endurance.

Objectives: Type 2 diabetes (T2D) and prediabetes are associated with poor walking endurance, a marker of physical function. We aimed to examine the long-term effects of metformin or intensive lifestyle intervention in adults at high risk of T2D on their 6-min walk test (6MWT) performance.

Methods: Participants were randomized in the 3-year Diabetes Prevention Program (DPP) to one of the three groups: lifestyle intervention, metformin, or placebo, and were subsequently followed in the DPP Outcomes Study.

Urinary Metal Levels, Cognitive Test Performance, and Dementia in the Multi-Ethnic Study of Atherosclerosis.

Importance: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

Objective: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

Design, Setting, And Participants: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018.

Association of circulating ketone bodies with cognitive performance and dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).

Introduction: Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases.

Methods: Associations of plasma KB with incident dementia and cognitive performances were examined among Multi-Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000-02) and detailed cognitive testing at Exam 5 (2010-2012,  = 4392), Exam 6 (2016-2018,  = 1838), and in MESA-MIND (2019-2021,  = 2060).

Metformin as a Potential Prevention Strategy for Alzheimer's Disease and Alzheimer's Disease Related Dementias.

Background: Metformin is a safe and effective medication for type 2 diabetes (T2D) that has been proposed to decrease the risk of aging related disorders including Alzheimer's disease (AD) and Alzheimer's disease related disorders(ADRD).

Objective: This review seeks to summarize findings from studies examining the association of metformin with AD/ADRD related outcomes.

Methods: This is a narrative review of human studies, including observational studies and clinical trials, examining the association of metformin with cognitive and brain outcomes.

Comparison of brief olfactory and cognitive assessments to neuroimaging biomarkers in the prediction of cognitive decline and dementia in the MCSA cohort.

Introduction: We evaluated impaired odor identification and global cognition as simple, cost-effective alternatives to neuroimaging biomarkers to predict cognitive decline and dementia in the Mayo Clinic Study of Aging.

Methods: Six hundred forty-seven participants (mean 8.1, standard deviation 3.

The lucidity in dementia experience: perspectives from family and professional caregivers.

Background: Family and professional caregivers of individuals with dementia often witness care-receiver's lucidity events.

Objective: A qualitative data analysis was performed of documented family and professional caregivers' experiences and their respective appraisals of lucidity events.

Research Design And Methods: Using a reduction method of selection, data from 10 in-home family caregivers and 20 professional caregivers to long-term care residents was content-coded and analysed.

Increased between-network connectivity: A risk factor for tau elevation and disease progression.

One of the pathologic hallmarks of Alzheimer's disease (AD) is neurofibrillary tau tangles. Despite our knowledge that tau typically initiates in the medial temporal lobe (MTL), the mechanisms driving tau to spread beyond MTL remain unclear. Emerging evidence reveals distinct patterns of functional connectivity change during aging and preclinical AD: while connectivity within-network decreases, connectivity between-network increases.

Plasma Biomarkers of Brain Injury and Their Association With Brain MRI and Cognition in Type 1 Diabetes.

Objective: To evaluate associations between plasma biomarkers of brain injury and MRI and cognitive measures in participants with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

Research Design And Methods: Plasma amyloid-β-40, amyloid-β-42, neurofilament light chain (NfL), phosphorylated Tau-181 (pTau-181), and glial fibrillary acidic protein (GFAP) were measured in 373 adults who participated in the DCCT/EDIC study. MRI assessments included total brain and white matter hyperintensity volumes, white matter mean fractional anisotropy, and indices of Alzheimer disease (AD)-like atrophy and predicted brain age.

Measurement of Allostatic Load in Caregivers of Older Hispanic People With Alzheimer Disease and Related Disorders.

Background: Allostatic load (AL) has been studied in the context of biomarkers that may be affected by environmental and contextual stressors, including social determinants of health. The specific stressor studied here is the provision of caregiving to older persons with Alzheimer disease and related disorders. The aims were to examine the factor structure of stress and nonstress biomarkers, different methods for calculating AL, and the relationship of AL with other variables.

Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial.

Objective: Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment.

Study Design: Randomized, controlled, single-site, early phase II, superiority trial.

Potentially Avoidable Hospitalizations Among Historically Marginalized Nursing Home Residents.

Importance: Nursing home (NH) transfers to hospitals are common and have been associated with cognitive decline; approximately 45% of NH hospital transfers are potentially avoidable hospitalizations (PAHs).

Objective: To determine PAH incidence for historically marginalized NH residents with severe cognitive impairment compared with non-Hispanic White residents.

Design, Setting, And Participants: This cross-sectional study merged 2018 Centers for Medicaid & Medicare Services datasets and LTCFocus, a public dataset on US NH care, for US NH residents aged 65 years and older who had a hospitalization.