Effect of transcranial direct current stimulation with cognitive training on executive functions in healthy older adults: a secondary analysis from the ACT trial.

Cognitive aging has become a public health concern as the mean age of the population is ever-increasing. It is a naturalistic and common process of degenerative and compensatory changes that may result in neurocognitive disorders. While heterogeneous, cognitive aging mostly affects executive functions that may be associated with functional losses during activities of daily living.

Neurocognitive correlates of cerebral mitochondrial function and energy metabolism using phosphorus magnetic resonance spectroscopy in older adults.

The goal of the current study was to learn about the role of cerebral mitochondrial function on cognition. Based on established cognitive neuroscience, clinical neuropsychology, and cognitive aging literature, we hypothesized mitochondrial function within a focal brain region would map onto cognitive behaviors linked to that brain region. To test this hypothesis, we used phosphorous (P) magnetic resonance spectroscopy (MRS) to derive indirect markers of mitochondrial function and energy metabolism across two regions of the brain (bifrontal, left temporal).

Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: a longitudinal observational study.

Background: Previous research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults.

Methods: Using 2005-2021 data from the National Alzheimer's Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit.

Clinical and Adverse Outcomes Associated With Concomitant Use of CYP2D6-Metabolized Opioids With Antidepressants in Older Nursing Home Residents : A Target Trial Emulation Study.

Background: Limited evidence exists on the safety of pharmacokinetic interactions of cytochrome P450 (CYP) 2D6 (CYP2D6)-metabolized opioids with antidepressants among older nursing home (NH) residents.

Objective: To investigate the associations of concomitant use of CYP2D6-metabolized opioids and antidepressants with clinical outcomes and opioid-related adverse events (ORAEs).

Design: Retrospective cohort study using a target trial emulation framework.

Plasma p-tau217 concordance with amyloid PET among ethnically diverse older adults.

Introduction: Commercially available plasma p-tau217 biomarker tests are not well studied in ethnically diverse samples.

Methods: We evaluated associations between ALZPath plasma p-tau217 and amyloid-beta positron emission tomography (Aβ-PET) in Hispanic/Latino (88% of Cuban or South American ancestry) and non-Hispanic/Latino older adults. One- and two-cutoff ranges were derived and evaluated to assess agreement with Aβ-PET.

Facilitation of working memory capacity by transcranial direct current stimulation: a secondary analysis from the augmenting cognitive training in older adults (ACT) study.

Aging is a public health concern with an ever-increasing magnitude worldwide. An array of neuroscience-based approaches like transcranial direct current stimulation (tDCS) and cognitive training have garnered attention in the last decades to ameliorate the effects of cognitive aging in older adults. This study evaluated the effects of 3 months of bilateral tDCS over the frontal cortices with multimodal cognitive training on working memory capacity.

Short- and long-term safety of discontinuing chronic opioid therapy among older adults with Alzheimer's disease and related dementia.

Background: Limited evidence exists on the short- and long-term safety of discontinuing versus continuing chronic opioid therapy (COT) among patients with Alzheimer's disease and related dementias (ADRD).

Methods: This cohort study was conducted among 162,677 older residents with ADRD and receipt of COT using a 100% Medicare nursing home sample. Discontinuation of COT was defined as no opioid refills for ≥90 days.

tDCS reduces depression and state anxiety symptoms in older adults from the augmenting cognitive training in older adults study (ACT).

Background: Pharmacological interventions for depression and anxiety in older adults often have significant side effects, presenting the need for more tolerable alternatives. Transcranial direct current stimulation (tDCS) is a promising non-pharmacological intervention for depression in clinical populations. However, its effects on depression and anxiety symptoms, particularly in older adults from the general public, are understudied.

Prevalence and trend of central nervous system-active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study.

Background: Limited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, depression, or epilepsy, conditions managed by CNS-active medications.

Methods: A multi-year, cross-sectional study using 2012-2021 MarketScan Commercial Claims data was conducted among adults aged 30 to 64 years with EOD and those without EOD but having a diagnosis of chronic pain, depression, or epilepsy as comparison groups. For each disease cohort, the primary outcome was CNS-active medication polypharmacy defined as concurrent use of ≥ 3 CNS-active medications on the US Beers Criteria list that overlapped for > 30 consecutive days during 12 months following a randomly selected medical encounter with the disease diagnosis.

Examining the relationship between anxiety and regional brain volumes in the National Alzheimer's Coordinating Center uniform, imaging, and biomarker datasets.

Anxiety has been associated with a greater risk of Alzheimer's disease (AD). Existing research has identified structural differences in regional brain tissue in participants with anxiety, but results have been inconsistent. We sought to determine the association between anxiety and regional brain volumes, and the moderation effect of APOE ε4.

Frontal-temporal regional differences in brain energy metabolism and mitochondrial function using P MRS in older adults.

Aging is a major risk for cognitive decline and transition to dementia. One well-known age-related change involves decreased brain efficiency and energy production, mediated in part by changes in mitochondrial function. Damaged or dysfunctional mitochondria have been implicated in the pathogenesis of age-related neurodegenerative conditions like Alzheimer's disease (AD).

Identification of Outcome-Oriented Progression Subtypes from Mild Cognitive Impairment to Alzheimer's Disease Using Electronic Health Records.

Alzheimer's disease (AD) is a complex heterogeneous neurodegenerative disease that requires an in-depth understanding of its progression pathways and contributing factors to develop effective risk stratification and prevention strategies. In this study, we proposed an outcome-oriented model to identify progression pathways from mild cognitive impairment (MCI) to AD using electronic health records (EHRs) from the OneFlorida+ Clinical Research Consortium. To achieve this, we employed the long short-term memory (LSTM) network to extract relevant information from the sequential records of each patient.

Free-water imaging reveals unique brain microstructural deficits in hispanic individuals with Dementia.

Prior evidence suggests that Hispanic and non-Hispanic individuals differ in potential risk factors for the development of dementia. Here we determine whether specific brain regions are associated with cognitive performance for either ethnicity along various stages of Alzheimer's disease. For this cross-sectional study, we examined 108 participants (61 Hispanic vs.

Pain intensity, physical function, and depressive symptoms associated with discontinuing long-term opioid therapy in older adults with Alzheimer's disease and related dementias.

Introduction: Limited evidence exists on the associations of discontinuing versus continuing long-term opioid therapy (LTOT) with pain intensity, physical function, and depression among patients with Alzheimer's disease and related dementias (ADRD).

Methods: A cohort study among 138,059 older residents with mild-to-moderate ADRD and receipt of LTOT was conducted using a 100% Medicare nursing home sample. Discontinuation of LTOT was defined as no opioid refills for ≥ 60 days.

Heterogeneous treatment effects of metformin on risk of dementia in patients with type 2 diabetes: A longitudinal observational study.

Introduction: Little is known about the heterogeneous treatment effects of metformin on dementia risk in people with type 2 diabetes (T2D).

Methods: Participants (≥ 50 years) with T2D and normal cognition at baseline were identified from the National Alzheimer's Coordinating Center database (2005-2021). We applied a doubly robust learning approach to estimate risk differences (RD) with a 95% confidence interval (CI) for dementia risk between metformin use and no use in the overall population and subgroups identified through a decision tree model.

Connecting memory and functional brain networks in older adults: a resting-state fMRI study.

Limited research exists on the association between resting-state functional network connectivity in the brain and learning and memory processes in advanced age. This study examined within-network connectivity of cingulo-opercular (CON), frontoparietal control (FPCN), and default mode (DMN) networks, and verbal and visuospatial learning and memory in older adults. Across domains, we hypothesized that greater CON and FPCN connectivity would associate with better learning, and greater DMN connectivity would associate with better memory.

Plasma Alzheimer's biomarkers and brain amyloid in Hispanic and non-Hispanic older adults.

Introduction: Alzheimer's disease studies often lack ethnic diversity.

Methods: We evaluated associations between plasma biomarkers commonly studied in Alzheimer's (p-tau181, GFAP, and NfL), clinical diagnosis (clinically normal, amnestic MCI, amnestic dementia, or non-amnestic MCI/dementia), and Aβ-PET in Hispanic and non-Hispanic older adults. Hispanics were predominantly of Cuban or South American ancestry.

Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer's disease risk.

The APOE 2/3/4 polymorphism is the greatest genetic risk factor for Alzheimer's disease (AD). This polymorphism is also associated with variation in plasma ApoE level; while APOE*4 lowers, APOE*2 increases ApoE level. Lower plasma ApoE level has also been suggested to be a risk factor for incident dementia.

Semantic intrusion errors are associated with plasma Ptau-181 among persons with amnestic mild cognitive impairment who are amyloid positive.

Introduction: Semantic intrusion errors (SI) have distinguished between those with amnestic Mild Cognitive Impairment (aMCI) who are amyloid positive (A+) versus negative (A-) on positron emission tomography (PET).

Method: This study examines the association between SI and plasma - based biomarkers. One hundred and twenty-eight participants received SiMoA derived measures of plasma pTau-181, ratio of two amyloid-β peptide fragments (Aβ42/Aβ40), Neurofilament Light protein (NfL), Glial Fibrillary Acidic Protein (GFAP), ApoE genotyping, and amyloid PET imaging.

Identification of Outcome-Oriented Progression Subtypes from Mild Cognitive Impairment to Alzheimer's Disease Using Electronic Health Records.

Alzheimer's disease (AD) is a complex heterogeneous neurodegenerative disease that requires an in-depth understanding of its progression pathways and contributing factors to develop effective risk stratification and prevention strategies. In this study, we proposed an outcome-oriented model to identify progression pathways from mild cognitive impairment (MCI) to AD using electronic health records (EHRs) from the OneFlorida+ Clinical Research Consortium. To achieve this, we employed the long short-term memory (LSTM) network to extract relevant information from the sequential records of each patient.

Stability in cognitive classification as a function of severity of impairment and ethnicity: A longitudinal analysis.

Objective: The interaction of ethnicity, progression of cognitive impairment, and neuroimaging biomarkers of Alzheimer's Disease remains unclear. We investigated the stability in cognitive status classification (cognitively normal [CN] and mild cognitive impairment [MCI]) of 209 participants (124 Hispanics/Latinos and 85 European Americans).

Methods: Biomarkers (structural MRI and amyloid PET scans) were compared between Hispanic/Latino and European American individuals who presented a change in cognitive diagnosis during the second or third follow-up and those who remained stable over time.