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Woojung Lee,1 Shelly L Gray,1 Douglas Barthold,1 Paul K Crane,2 Eric B Larson,3 Zachary A Marcum1 1School of Pharmacy, University of Washington, Seattle, WA 98195, USA; 2School of Medicine, University of Washington, Seattle, WA 98104, USA; 3Kaiser Permanente Washington Health Research Institute, Seattle, WA 98101, USACorrespondence: Zachary A MarcumDepartment of Pharmacy, School of Pharmacy, University of Washington, 1959 NE Pacific St, Box 357630, Seattle, WA 98102, USATel +1 206-685-2559Fax +1 206-543-3835Email zmarcum@uw.edu Twitter @zacharyamarcumPurpose: Antihypertensives may have effects on the brain beyond blood pressure lowering. Ongoing clinical trials aim to evaluate the effectiveness of approved antihypertensives in preventing dementia, including patients with and without hypertension. In order for a dementia prevention strategy using antihypertensives to be effective, it is critical to understand patient concerns about this strategy in both users and non-users of antihypertensives. Thus, this study examined the association between current use of antihypertensive and having concerns about using an antihypertensive as a dementia prevention strategy, as well as sociodemographic factors associated with concerns.Patients and methods: Cross-sectional, self-administered, web-based survey was conducted among 1661 patients in a large health system in January 2018. Participants reported whether they were currently taking an antihypertensive (yes/no), and what types of hypothetical concerns they have about the idea of taking an antihypertensive to prevent dementia (yes/no, for each of 7 concerns). Associations between the two variables were assessed via logistic regression, and odds ratios with 95% confidence intervals were calculated.Results: Most respondents were female (77%), 51–70 years of age (64%), and white (89%), with 30% reporting current antihypertensive use. Compared to current users, non-users were more likely to report the five following concerns: side effects from the medication, hassle to take medications, lack of evidence, not wanting to use medications, and already having normal/low blood pressure. Non-users were also less likely to report having no concerns (adjusted OR = 0.3; 95% CI = 0.2–0.4) compared to current users. Younger age and lower income were associated with having more concerns.Conclusion: Patients not currently using an antihypertensive are more likely to have concerns about using an antihypertensive for dementia prevention, compared to current antihypertensive users. Patient perspectives are important to consider for the implementation of dementia prevention strategies.Keywords: dementia, antihypertensives, primary prevention, patient concerns, patient perspectives

Social support (SS) predicts health outcomes among patients living with HIV. We administered a brief, validated measure of SS, the Multifactoral Assessment of Perceived Social Support, within a patient-reported outcomes assessment of health domains in HIV care at 4 U.S. clinics in English and Spanish (n = 708). In univariate analysis, low SS was associated with poorer engagement in care, antiretroviral adherence, and health-related quality of life; current methamphetamine/crystal use, depression, anxiety, and HIV stigma (all p

We assessed acceptability/usability of tablet-based patient-reported outcome (PRO) assessments among patients in HIV care, and relationships with health outcomes using a modified Acceptability E-Scale (AES) within a self-administered PRO assessment. Using multivariable linear regression, we measured associations between patient characteristics and continuous combined AES score. Among 786 patients (median age=48; 91% male; 49% white; 17% Spanish-speaking) overall mean score was 26/30 points (SD: 4.4). Mean scores per dimension (max 5, 1=lowest acceptability, 5=highest): ease of use 4.7, understandability 4.7, time burden 4.3, overall satisfaction 4.3, helpfulness describing symptoms/behaviors 4.2, and enjoyability 3.8. Higher overall score was associated with race/ethnicity (+1.3 points/African-American patients (95%CI:0.3-2.3); +1.6 points/Latino patients (95%CI:0.9-2.3) compared to white patients). Patients completing PROs in Spanish scored +2.4 points on average (95%CI:1.6-3.3). Higher acceptability was associated with better quality of life (0.3 points (95%CI:0.2-0.5)) and adherence (0.4 points (95%CI:0.2-0.6)). Lower acceptability was associated with: higher depression symptoms (-0.9 points (95%CI:-1.4 to -0.4)); recent illicit opioid use (-2.0 points (95%CI:-3.9 to -0.2)); multiple recent sex partners (-0.8 points (95%CI:-1.5 to -0.1)). While patients endorsing depression symptoms, recent opioid use, condomless sex, or multiple sex partners found PROs less acceptable, overall, patients found the assessments highly acceptable and easy to use.

BackgroundProviders are often unaware of poor adherence to prescribed medications for their patients with chronic diseases.ObjectiveTo develop brief, computer-administered patient-reported measures in English and Spanish assessing adherence behaviors and barriers. Design, Participants, and Main Measures: Item pools were constructed from existing measures of medication adherence behaviors and barriers, which informed development of a patient concept elicitation interview guide to identify medication adherence behavior and barrier-related concepts. Two hundred six patients either living with HIV (PLWH) or without were interviewed. Interviews were coded, concepts matched to item pool content, and new items were developed for novel concepts. A provider/investigator team highlighted clinically relevant items. Cognitive interviews were conducted with patients on final candidate items (n = 37). The instruments were administered to 2081 PLWH.Key resultsBehavioral themes from concept elicitation interviews included routines incorporating time of day, placement, visual cues, and intentionality to miss or skip doses. Barrier themes included health-related (e.g. depressed mood, feeling ill), attitudes/beliefs (e.g., need for medication), access (e.g., cost/insurance problems), and circumstantial barriers (e.g., lack of privacy, disruption of daily routine). The final instruments included 6 behavior items, and 1 barrier item with up to 23 response options. PLWH endorsed a mean (SD) of 3.5 (1.1) behaviors. The 201 PLWH who missed ≥2 doses in the previous week endorsed a mean (SD) of 3.1 (2.5) barriers. The intraclass correlation coefficient (ICC) for the numbers of behaviors endorsed in 61 PLWH after 4-16 days was 0.54 and for the number of barriers for the 20 PLWH with ≥2 missed doses the ICC was 0.89, representing fair and excellent test-retest reliability.ConclusionMeasures of medication adherence behaviors and barriers were developed for use with patients living with chronic diseases focusing on clinical relevance, brevity, and content validity for use in clinical care.

IntroductionRates of sexually transmitted infection (STI) are rising in the USA, yet STI risk remains under-addressed by providers, even in HIV care, and with high-risk patients. We interviewed primary care patients living with and without HIV regarding circumstances surrounding sexual risk behavior to identify opportunities for providers to address and reduce STI risk.MethodsWe conducted semi-structured 1:1 interviews with patients living with and without HIV reporting ≥ 1 sex partner and varying STI exposure risk in the past 12 months from four geographically diverse US HIV and primary care clinics. We audio-recorded, transcribed, and coded interviews by circumstance type, using double-coding to ensure inter-coder reliability. We used Fisher's exact and T tests to determine associations with demographic/risk factors.ResultsPatients (n = 91) identified a mean of 3 of 11 circumstances. These included substance use (54%), desire for physical/emotional intimacy (48%), lack of HIV/STI status disclosure (44%), psychological drivers (i.e., coping, depression; 38%), personal dislike of condoms (22%), partner condom dislike/refusal (19%), receiving payment for sex (13%), and condom unavailability (9%). Higher proportions of those who were high STI-exposure risk patients, defined as those with ≥ 2 sex partners in the past 3 months reporting never or sometimes using condoms, reported disliking condoms (p = .006); higher proportions of the high-risk and moderate-risk (≥ 2 partners and condom use "most of the time") groups reported substance use as a circumstance (p = .04).ConclusionCircumstances surrounding perceived STI exposure risk were diverse, often overlapping, and dependent on internal, environmental, and partner-related factors and inadequate communication. Meaningful care-based interventions regarding HIV/STI transmission behavior must address the diversity and interplay of these factors.

BackgroundLow health literacy is associated with poor medication adherence and poor health outcomes. Limited understanding of prescribed medications may decrease validity of patient-reported adherence measures.ObjectivesTo assess knowledge of names and purposes of prescribed medications among patients with multiple chronic conditions.MethodsIndividual interviews were conducted with a convenience sample of patients from six U.S. primary care clinics. Participants (n = 57) were English and/or Spanish-speaking patients prescribed 3+ medications for chronic conditions, for which non-adherence may lead to disability or death. In individual interviews, patients were asked to name their medications, explain the purpose of each, and to explain how they distinguish them from one another. Interviews were audio recorded, transcribed, and coded; coded content was quantified by 1) whether or not the patient could name medications; 2) method of categorizing medications; 3) whether or not the purpose of the medication was understood. Descriptive statistics were compiled using Fisher's exact test to determine the relationship between patient knowledge and medication characteristics.ResultsThirty percent of patients could not name at least one of their medications; 19% did not know their purpose; 30% held misconceptions about the purpose of one or more medications. There was no significant difference in ability to name medications or state their medication's purpose between patients using medi-sets, pre-packaged rolls, or blister packs, and patients who stored pills in their original containers (p = 0.56 and p = 0.73, respectively), or across demographic groups (p = 0.085 to 0.767).ConclusionsMany patients demonstrated difficulty identifying the name and purpose of prescribed medications; this did not differ by demographic group or medication storage type. Patients may benefit from routine review of medications with their provider in order to improve health literacy, outcomes, and patient-reported adherence measurement.

PurposeTo evaluate psychometric characteristics and cross-sectional and longitudinal validity of the 7-item PROMIS® Fatigue Short Form and additional fatigue items among people living with HIV (PLWH) in a nationally distributed network of clinics collecting patient reported data at the time of routine clinical care.MethodsCross-sectional and longitudinal fatigue data were collected from September 2012 through April 2013 across clinics participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We analyzed data regarding psychometric characteristics including simulated computerized adaptive testing and differential item functioning, and regarding associations with clinical characteristics.ResultsWe analyzed data from 1597 PLWH. Fatigue was common in this cohort. Scores from the PROMIS® Fatigue Short Form and from the item bank had acceptable psychometric characteristics and strong evidence for validity, but neither performed better than shorter instruments already integrated in CNICS.ConclusionsThe PROMIS® Fatigue Item Bank is a valid approach to measuring fatigue in clinical care settings among PLWH, but in our analyses did not perform better than instruments associated with less respondent burden.

APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.

We developed, implemented, and evaluated a myocardial infarction (MI) adjudication protocol for cohort research of human immunodeficiency virus. Potential events were identified through the centralized Centers for AIDS Research Network of Integrated Clinical Systems data repository using MI diagnoses and/or cardiac enzyme laboratory results (1995-2012). Sites assembled de-identified packets, including physician notes and results from electrocardiograms, procedures, and laboratory tests. Information pertaining to the specific antiretroviral medications used was redacted for blinded review. Two experts reviewed each packet, and a third review was conducted if discrepancies occurred. Reviewers categorized probable/definite MIs as primary or secondary and identified secondary causes of MIs. The positive predictive value and sensitivity for each identification/ascertainment method were calculated. Of the 1,119 potential events that were adjudicated, 294 (26%) were definite/probable MIs. Almost as many secondary (48%) as primary (52%) MIs occurred, often as the result of sepsis or cocaine use. Of the patients with adjudicated definite/probable MIs, 78% had elevated troponin concentrations (positive predictive value = 57%, 95% confidence interval: 52, 62); however, only 44% had clinical diagnoses of MI (positive predictive value = 45%, 95% confidence interval: 39, 51). We found that central adjudication is crucial and that clinical diagnoses alone are insufficient for ascertainment of MI. Over half of the events ultimately determined to be MIs were not identified by clinical diagnoses. Adjudication protocols used in traditional cardiovascular disease cohorts facilitate cross-cohort comparisons but do not address issues such as identifying secondary MIs that may be common in persons with human immunodeficiency virus.

Subjective cognitive complaints (SCCs) are increasingly a focus in studies on prodromal Alzheimer disease (AD) and risk for dementia. Little is known about the optimal approach to measure SCCs. We used item response theory (IRT) to examine the characteristics of 24 SCC items in a sample of 3495 older adults pooled from 4 community-based studies. We investigated the potential advantages of IRT scoring over conventional scoring on the basis of participants' item response patterns. Items most likely endorsed by individuals low in SCC severity relate to word retrieval and general subjective memory decline. Items likely endorsed only by individuals high in SCC severity relate to nonepisodic memory changes, such as decline in comprehension, judgment and executive functions, praxis and procedural memory, and social behavior changes. Above and beyond conventional total score, IRT scoring of SCCs was associated with performance on objective cognitive tests, and was associated with cognitive test performance among participants endorsing only 1 SCC item. Thus, IRT scoring captures additional information beyond a simple sum of SCC symptoms. Modern psychometric approaches including IRT may be useful in developing: (1) brief community screening questionnaires; and (2) more sensitive measures of very subtle subjective decline for use in prodromal Alzheimer disease research. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and other dementias are likely preceded by a protracted preclinical state. Thus, identification of biomarkers that signal potential points of intervention during this prodromal phase (during which patients are largely able to compensate for their cognitive deficits) is of paramount importance. Insulin is a pancreatic hormone with potent central nervous system effects, and insulin dysregulation has been implicated in the pathogenesis of both AD and vascular dementia. The aim of the current study was to determine whether circulating insulin differs as a function of mild cognitive impairment (MCI) diagnosis, and whether this relationship is mediated by sex and apolipoprotein E (APOE) genotype. A sample of 549 nondemented participants aged 65 and over from the Adult Changes in Thought community-based cohort underwent cognitive testing and blood draw to determine fasting levels of plasma insulin. Subjects were categorized as having normal cognitive functioning, amnestic MCI, or nonamnestic MCI. Results showed that the relationship between insulin and diagnostic category is moderated by sex, such that men with nonamnestic or amnestic MCI have higher fasting plasma insulin than cognitively normal men, while women with amnestic MCI have lower fasting plasma insulin than cognitively normal women. Exploratory analyses suggest that APOE ε4 genotype may further influence the relationship between sex and insulin. Future research will help determine whether insulin dysregulation results in differential effects on vascular function and AD pathology as a function of sex and/or APOE genotype. [ABSTRACT FROM AUTHOR]

Objective: To evaluate psychometric properties of a widely used patient experience survey.Data Sources: English-language responses to the Clinician & Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS®) survey (n = 12,244) from a 2008 quality improvement initiative involving eight southern California medical groups.Methods: We used an iterative hybrid ordinal logistic regression/item response theory differential item functioning (DIF) algorithm to identify items with DIF related to patient sociodemographic characteristics, duration of the physician-patient relationship, number of physician visits, and self-rated physical and mental health. We accounted for all sources of DIF and determined its cumulative impact.Principal Findings: The upper end of the CG-CAHPS® performance range is measured with low precision. With sensitive settings, some items were found to have DIF. However, overall DIF impact was negligible, as 0.14 percent of participants had salient DIF impact. Latinos who spoke predominantly English at home had the highest prevalence of salient DIF impact at 0.26 percent.Conclusions: The CG-CAHPS® functions similarly across commercially insured respondents from diverse backgrounds. Consequently, previously documented racial and ethnic group differences likely reflect true differences rather than measurement bias. The impact of low precision at the upper end of the scale should be clarified. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) is proposed to be a prodrome to dementia in some older adults. However, the presentation of MCI in the community can differ substantially from clinic-based samples. The aim of the current study is to demonstrate the effects of different operational definitions of MCI on prevalence estimates in community-dwelling older adults. A consecutive series of 200 participants aged 65 and over from the Adult Changes in Thought (ACT) community-based cohort were approached to undergo comprehensive neuropsychological and medical evaluation; 159 were included in the final analyses. Nondemented subjects were categorized using various diagnostic criteria for MCI. In a novel approach, neuropsychological test scores were evaluated using an individualized benchmark as a point of test comparison, as well as traditional methods that entail comparison to age-based normative data. Diagnostic criteria were further subdivided by severity of impairment (1.0 vs. 1.5 standard deviations [sd] below the benchmark) and extent of impairment (based on a single test or an average of tests within a cognitive domain). MCI prevalence rates in the sample were highly dependent on these diagnostic factors, and varied from 11% to 92% of the sample. Older groups tended to show higher prevalence rates, although this was not the case across all diagnostic schemes. The use of an individualized benchmark, less severe impairment cutoff, and impairment on only a single test all produced higher rates of MCI. Longitudinal follow-up will determine whether varying diagnostic criteria improves sensitivity and specificity of the MCI diagnosis as a predictor for dementia. [ABSTRACT FROM AUTHOR]

Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study. [ABSTRACT FROM AUTHOR]

Little is known about the psychometric properties of depression instruments among persons infected with HIV. We analyzed data from a large sample of patients in usual care in two US cities (n=1467) using the nine-item Patient Health Questionnaire (PHQ-9) from the PRIME-MD. The PHQ-9 had curvilinear scaling properties and varying levels of measurement precision along the continuum of depression measured by the instrument. In our cohort, the scale showed a prominent floor effect and a distribution of scores across depression severity levels. Three items had differential item functioning (DIF) with respect to race (African-American vs. white); two had DIF with respect to sex; and one had DIF with respect to age. There was minimal individual-level DIF impact. Twenty percent of the difference in mean depression levels between African-Americans and whites was due to DIF. While standard scores for the PHQ-9 may be appropriate for use with individual HIV-infected patients in cross-sectional settings, these results suggest that investigations of depression across groups and within patients across time may require a more sophisticated analytic framework. [ABSTRACT FROM AUTHOR]

Background: Differential item functioning (DIF) exists when test item responses by members of different demographic groups are statistically different when controlling for ability. DIF may indicate item bias. Our objective was to determine whether items from the Italian Mini-mental State Examination (MMSE) had DIF related to educational attainment, age, gender and occupation. We were also interested in exploring the significance of DIF in screening tests.Methods: In a two-stage study from Granarolo, Italy, residents over age 61 (n = 495) were evaluated with the Italian MMSE. Those with MMSE scores of 28 or lower were further evaluated for dementia. MMSE results were coded in 10 item bundles. We used ordinal logistic regression to determine whether item bundles had DIF.Results: Six of the 10 MMSE item bundles had DIF in educational attainment subgroups. Four of these six bundles also had DIF related to age. Items that required literacy were much harder for those with lower educational attainment.Conclusions: DIF related to education appeared at as few as 3 years of formal schooling. These findings suggest cautious interpretation of data from studies using the Italian MMSE in populations with heterogeneous educational backgrounds. DIF is especially troublesome for two-stage studies that use screening tests. [ABSTRACT FROM AUTHOR]

Introduction: We present an ordinal logistic regression model for identification of items with differential item functioning (DIF) and apply this model to a Mini-Mental State Examination (MMSE) dataset. We employ item response theory ability estimation in our models. Three nested ordinal logistic regression models are applied to each item. Model testing begins with examination of the statistical significance of the interaction term between ability and the group indicator, consistent with nonuniform DIF. Then we turn our attention to the coefficient of the ability term in models with and without the group term. If including the group term has a marked effect on that coefficient, we declare that it has uniform DIF. We examined DIF related to language of test administration in addition to self-reported race, Hispanic ethnicity, age, years of education, and sex.Methods: We used PARSCALE for IRT analyses and STATA for ordinal logistic regression approaches. We used an iterative technique for adjusting IRT ability estimates on the basis of DIF findings.Results: Five items were found to have DIF related to language. These same items also had DIF related to other covariates.Discussion: The ordinal logistic regression approach to DIF detection, when combined with IRT ability estimates, provides a reasonable alternative for DIF detection. There appear to be several items with significant DIF related to language of test administration in the MMSE. More attention needs to be paid to the specific criteria used to determine whether an item has DIF, not just the technique used to identify DIF. [ABSTRACT FROM AUTHOR]

Background: Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians., Methods: Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally., Results: Baseline analyses revealed that amyloid-negative (Aβ-) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ- CN individuals with low FRS (p < 0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups., Conclusion: Our findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ- individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid-positive individuals had worse cognitive performance than Aβ- individuals., Highlights: Vascular risk significantly affects cognition in amyloid-negative older Koreans. Amyloid-negative CN older adults with high vascular risk had lower baseline cognition. Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk. The study underscores the impact of vascular health on the AD disease spectrum., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies. This cohort includes 33 male donors and 51 female donors, with an average age at time of death of 88 years. We used quantitative neuropathology to place donors along a disease pseudoprogression score. Pseudoprogression analysis revealed two disease phases: an early phase with a slow increase in pathology, presence of inflammatory microglia, reactive astrocytes, loss of somatostatin + inhibitory neurons, and a remyelination response by oligodendrocyte precursor cells; and a later phase with exponential increase in pathology, loss of excitatory neurons and Pvalb + and Vip + inhibitory neuron subtypes. These findings were replicated in other major AD studies., (© 2024. The Author(s).)

This study protocol describes the development of the first instrument of functional communication for people living with primary progressive aphasia (PPA), with future applications to other progressive conditions, with expert validation, item-level reliability analyses, input from partners in research, and outcomes. Progressive conditions like PPA require monitoring, and as such, re-assessment. Re-assessment poses the high risk of being burdensome, destructive, and of little use to the patient. As such, there is a significant need to establish a validated and reliable measure that (1) poses minimal patient burden and (2) captures communication ability in a strengths-based manner for both clinical and research purposes. A strengths-based approach to assessment is widely recognized as the optimal way to promote patient autonomy, minimize harm, and implement functional treatment protocols and strategies. To date, there are no strengths-based assessment tools that were developed for people living with PPA nor ways to efficiently document functional communication performance. This study protocol outlines our work to address this gap in clinical practice and research., Competing Interests: The authors have declared that no competing interests exist. The experimental approach described in this manuscript is supported by a 2024-2025 University of Washington Alzheimer’s Disease Research Center Development Project Award (JG). This work was also supported by the National Institute on Aging (U24 AG074855: JG & PKC; P30 AG066509: KDR)., (Copyright: © 2024 Gallée et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Changes in sleep, physical activity and mental health were observed in older adults during early stages of the COVID-19 pandemic. Here we describe effects of the COVID-19 pandemic on older adult mental health, wellbeing, and lifestyle behaviors and explore predictors of better mid-pandemic mental health and wellbeing., Methods: Participants in the Adult Changes in Thought study completed measures of lifestyle behaviors (e.g., sleep, physical activity) and mental health and wellbeing both pre-pandemic during regular study visits and mid-pandemic via a one-time survey. We used paired t-tests to compare differences in these measures pre- vs. mid-pandemic. Using multivariate linear regression, we further explored demographic, health, and lifestyle predictors of pandemic depressive symptoms, social support, and fatigue. We additionally qualitatively coded free text data from the mid-pandemic survey for related comments., Results: Participants (N = 896) reported significant changes in mental health and lifestyle behaviors at pre-pandemic vs. mid-pandemic measurements (p < 0.0001). Qualitative findings supported these behavioral and wellbeing changes. Being male, never smoking, and lower pre-pandemic computer time and sleep disturbance were significantly associated with lower pandemic depressive symptoms. Being partnered, female, never smoking, and lower pre-pandemic sleep disturbance were associated with higher pandemic social support. Pre-pandemic employment, more walking, less computer time, and less sleep disturbance were associated with less pandemic fatigue. Participant comments supported these quantitative findings, highlighting gender differences in pandemic mental health, changes in computer usage and physical activity during the pandemic, the value of spousal social support, and links between sleep disturbance and mental health and wellbeing. Qualitative findings also revealed additional factors, such as stresses from personal and family health situations and the country's concurrent political environment, that impacted mental health and wellbeing., Conclusions: Several demographic, health, and lifestyle behaviors appeared to buffer the effects of the COVID-19 pandemic and may be key sources of resilience. Interventions and public health measures targeting men and unpartnered individuals could promote social support resilience, and intervening on modifiable behaviors like sleep quality, physical activity and sedentary activities like computer time may promote resilience to fatigue and depressive symptoms during future community stressor events. Further research into these relationships is warranted., (© 2024. The Author(s).)

Aim: To examine cross-sectional associations between continuous glucose monitoring (CGM)-derived metrics and cerebral small vessel disease (SVD) in older adults with type 2 diabetes., Materials and Methods: In total, 80 patients with type 2 diabetes aged ≥70 years were analysed. Participants underwent CGM for 14 days. From the CGM data, we derived mean sensor glucose, percentage glucose coefficient of variation, mean amplitude of glucose excursion, time in range (TIR, 70-180 mg/dl), time above range (TAR) and time below range metrics, glycaemia risk index and high/low blood glucose index. The presence of cerebral SVD, including lacunes, microbleeds, enlarged perivascular spaces and white matter hyperintensities, was assessed, and the total number of these findings comprised the total cerebral SVD score (0-4). Ordinal logistic regression analyses were performed to examine the association of CGM-derived metrics with the total SVD score., Results: The median SVD score was 1 (interquartile range 0-2). Higher hyperglycaemic metrics, including mean sensor glucose, TAR >180 mg/dl, TAR >250 mg/dl, and high blood glucose index and glycaemia risk index, were associated with a higher total SVD score. In contrast, a higher TIR (per 10% increase) was associated with a lower total SVD score (odds ratio 0.73, 95% confidence interval 0.56-0.95). Glycated haemoglobin, percentage glucose coefficient of variation, mean amplitude of glucose excursions, time below range and low blood glucose index were not associated with total cerebral SVD scores., Conclusions: The hyperglycaemia metrics and TIR, derived from CGM, were associated with cerebral SVD in older adults with type 2 diabetes., (© 2024 John Wiley & Sons Ltd.)

Throughout an organism's life, a multitude of complex and interdependent biological systems transition through biophysical processes that serve as indicators of the underlying biological states. Inferring these latent, unobserved states is a goal of modern biology and neuroscience. However, in many experimental setups, we can at best obtain discrete snapshots of the system at different times and for different individuals. This challenge is particularly relevant in the study of Alzheimer's Disease (AD) progression, where we observe the aggregation of pathology in brain donors, but the underlying disease state is unknown. This paper proposes a biophysically motivated Bayesian framework (B-BIND: Biophysical Bayesian Inference for Neurodegenerative Dynamics), where the disease state is modeled and continuously inferred from observed quantifications of multiple AD pathological proteins. Inspired by biophysical models, we describe pathological burden as an exponential process. The progression of AD is modeled by assigning a latent score, termed pseudotime, to each pathological state, creating a pseudotemporal order of donors based on their pathological burden. We study the theoretical properties of the model using linearization to reveal convergence and identifiability properties. We provide Markov chain Monte Carlo estimation algorithms, illustrating the effectiveness of our approach with multiple simulation studies across various data conditions. Applying this methodology to data from the Seattle Alzheimer's Disease Brain Cell Atlas, we infer the pseudotime ordering of donors. Finally, we analyze the information within each pathological feature to refine the model, focusing on the most informative pathologies. This framework lays the groundwork for continuous pseudotime modeling in the analysis of neurodegenerative diseases.