Alzheimer Disease and Related Dementia Following Hormone-Modulating Therapy in Patients With Breast Cancer.

Importance: Hormone-modulating therapy (HMT) is a widely accepted treatment for hormone receptor-positive breast cancer, although its cognitive effects, including a potential link to Alzheimer disease and related dementias (ADRD), remain understudied. Objective: To investigate the association between HMT for breast cancer treatment and risk of developing ADRD in women aged 65 years or older. Design, Setting, and Participants: This cohort study used a comprehensive dataset from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to identify patients who did and did not receive HMT treatment within 3 years after the initial diagnosis of breast cancer and assessed their risk of developing ADRD in later life. Individuals with a preexisting diagnosis of ADRD or receiving HMT before the diagnosis of breast cancer were excluded. This study was performed from June 2022 through January 2024. Exposure: Receipt of HMT. Main Outcomes and Measures: Risk of ADRD associated with HMT; associations of risk with age, self-identified race, and HMT type. Risk was measured using hazard ratios (HRs) with 95% CIs and adjusted for potential confounders such as demographic, sociocultural, and clinical variables. Results: Among 18 808 women aged 65 years and older diagnosed with breast cancer between 2007 and 2009 (1266 Black [6.7%], 16 526 White [87.9%], 1016 other [5.4%]), 12 356 (65.7%) received HMT within 3 years after diagnosis, while 6452 (34.3%) did not. The most common age group in both samples was the 75 to 79 years age group (HMT, 2721 women [22.0%]; no HMT, 1469 women [22.8%]), and the majority of women in both groups self-identified as White (HMT, 10 904 women [88.3%]; no HMT, 5622 women [87.1%]). During an average of 12 years of follow-up, 2926 (23.7%) of HMT users and 1802 (27.9%) of non-HMT users developed ADRD. HMT was associated with a 7% lower relative risk of ADRD overall (HR, 0.93; 95% CI, 0.88-0.98; P = .005). The association decreased with age and varied by race. The reduction in ADRD risk associated with HMT was greatest for women aged 65 to 74 years who self-identified as Black (HR, 0.76; 95% CI, 0.62-0.92). This association decreased among women aged 75 years or older (HR, 0.81; 95% CI, 0.67-0.98). Women aged 65 to 74 years who self-identified as White had an 11% relative risk reduction (HR, 0.89; 95% CI, 0.81-0.97), but the association disappeared for women aged 75 years or older (HR, 0.96; 95% CI, 0.90-1.02). Other races showed no significant association between HMT and ADRD. Age- and race-based associations also varied by HMT type. Conclusions and Relevance: In this retrospective cohort study, hormone therapy was associated with protection against ADRD in women aged 65 years or older with newly diagnosed breast cancer; the decrease in risk was relatively greater for Black women and women under age 75 years, while the protective effect of HMT diminished with age and varied by race in women. When deciding to use HMT for breast cancer in women aged 65 years or more, clinicians should consider age, self-identified race, and HMT type in treatment decisions.

Comparing COVID-19 vaccination coverage, adverse reactions and impact of social determinants of health on vaccine hesitancy in ADRD/MCI and non-ADRD/MCI population: protocol for a retrospective cross-sectional study.

INTRODUCTION: COVID-19 vaccination is crucial for vulnerable people with underlying chronic conditions such as Alzheimer's disease and related dementias (ADRD) and mild cognitive impairment (MCI). These individuals face unique challenges, including higher risk of COVID-19, difficulties in adopting preventive behaviours and vaccine hesitancy due to concerns about adverse reactions. Therefore, efforts to promote vaccination, including boosters tailored to the currently circulating virus, are essential for people with ADRD/MCI. OBJECTIVE: The primary purpose of this study protocol is to conduct a comprehensive analysis of COVID-19 vaccination coverage and adverse reactions among individuals with ADRD/MCI in comparison to those without ADRD/MCI. Additionally, the proposed study aims to investigate the impact of social determinants of health on COVID-19 vaccination and vaccine hesitancy in individuals with ADRD/MCI. METHODS AND ANALYSIS: A retrospective cross-sectional study will be conducted utilising data from the All of Us (AoU) Researcher Workbench. Relevant data fields are extracted from sources including demographic information, COVID-19 Vaccine Survey, Basic Survey, Health Access & Utilization, Social Determinants of Health, and Electronic Health Record (EHR) data. Data on vaccination, adverse reactions and vaccine hesitancy will be collected through COVID-19 vaccine survey questionnaires. Propensity score matching and binary logistic regression will be applied to assess the vaccination rates and vaccine hesitancy, while controlling for demographic characteristics and social determinants of health factors. ETHICS AND DISSEMINATION: This study protocol received approval from the Institutional Review Board at Florida State University (STUDY00004571). Results will be disseminated through publication in peer-reviewed journals and presented at scientific conferences.

The association between rurality, places of care and the location of death of long-term care home residents with dementia: A population-based study.

Background: Most individuals prefer to spend their final moments of life outside a hospital setting. This study compares the places of care and death of long-term care (LTC) home residents in Ontario in the last 90 days of life, according to LTC home rurality. Data and methods: This retrospective cohort study was conducted using health administrative data from ICES (formerly known as the Institute for Clinical Evaluative Sciences). The study population, which was identified through algorithms, included all Ontario LTC home residents with a dementia diagnosis who died between April 1, 2014, and March 31, 2019. The location of death was categorized as in an acute care hospital, an LTC home, a subacute care facility, or the community. Places of care included emergency department visits and hospitalizations in the last 90 days of life. Statistical tests were used to evaluate differences in location of death and places of care by rurality. Results: Of the 65,375 LTC home residents with dementia, 49,432 (75.6%) died in an LTC home. Residents of LTC homes in the most urban areas were less likely to die in an LTC home than those in more rural homes (adjusted relative risk: 0.84; 95% confidence interval: 0.83 to 0.85). A higher proportion of residents of the most urban LTC homes had at least one hospitalization in the last 90 days of life compared with rural residents (23.7% versus 9.9% palliative hospitalizations and 28.3% versus 15.9% non-palliative hospitalizations [p ⟨ 0.001]). Interpretation: Individuals with dementia residing in urban LTC homes are more likely to receive care in the hospital and to die outside a LTC home than their counterparts living in rural LTC homes. The findings of this work will inform efforts to improve end-of-life care for older adults with dementia living in LTC homes.

A systematic review of digital access to post-diagnostic health and social care services for dementia.

OBJECTIVES: For many people with dementia and unpaid carers, using technology for care and support has become essential. Rapid proliferation of technology highlights the need to understand digital access to health and social care services for dementia. This mixed-methods systematic review aims to explore digital access to health and social care services for dementia, from the perspective of people with dementia and unpaid carers. METHODS: Nine electronic databases were searched in May 2023 for qualitative, quantitative, or mixed-method studies, published in English or German, focused on experiences of using technology-delivered health and social care services for people with dementia and unpaid carers. After removal of duplicates and screening, 44 empirical papers were included. RESULTS: From the 44 studies, findings were grouped into five categories, highlighting experiences for people with dementia and unpaid carers: (1) Adapting to technology, (2) Inequalities and variations in outcomes, (3) Impact on caring, (4) Impact on health, and (5) Impact on relationships. Proliferation of technology in care access emphasised the need for quick adaptation to technology and examination of its impact. The impact of such service delivery has evidenced mixed findings. There were improvements in the health and wellbeing of people with dementia and unpaid carers, and benefits for their dyadic relationship. However, using technology for health and social care access is not always possible and is often reliant on unpaid carers for support. Lower tech-literacy, lack of equipment or money to buy equipment and poor internet connection can impact the potential for positive outcomes. CONCLUSIONS: Technology can bring great benefits: social inclusion, improved service access and care. However, using technology in service delivery in dementia needs careful thought. Professionals and service providers need to be cognizant of the complex nature of dementia, and the benefits and challenges of hybrid service delivery.

A Randomized Controlled Clinical Trial Investigating the Weaning Process From Mechanical Ventilation in Elderly Patients With Dementia.

BACKGROUND: Limited data is available regarding the weaning techniques employed for mechanical ventilation (MV) in elderly patients with dementia in China. OBJECTIVE: The primary objective of this study is to investigate diverse weaning methods in relation to the prognostic outcomes of elderly patients with dementia undergoing MV in the intensive care unit (ICU). Specifically, we seek to compare the prognosis, likelihood of successful withdrawal from MV, and the length of stay (LOS) in the ICU. METHODS: The study was conducted as a randomized controlled trial, encompassing a group of 169 elderly patients aged ≥ 65 years with dementia who underwent MV. Three distinct weaning methods were used for MV cessation, namely, the tapering parameter, spontaneous breathing trial (SBT), and SmartCare (Dräger, Germany). RESULTS: In the tapering parameter group, the LOS in the ICU was notably prolonged compared to both the SBT and SmartCare groups. However, no statistically significant differences were observed among the groups with respect to demographic characteristics, such as age and sex, as well as factors including the rationale for ICU admission, cause of MV, MV mode, oxygenation index, hemoglobin levels, albumin levels, ejection fraction, sedation and analgesia practices, tracheotomy, duration of MV, successful extubation, successful weaning, incidences of ventilator-associated pneumonia, and overall prognosis. CONCLUSIONS: Both the SBT and SmartCare withdrawal methods demonstrated a reduction in the duration of MV and LOS in the ICU when compared to the tapering parameter method. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900028449.

Psychological distress among family caregivers of persons with Alzheimer's disease and related dementias in Uganda.

BACKGROUND: Alzheimer's disease and related dementias (ADRD) present growing global health challenges, especially in aging populations, such as Uganda. In Uganda, familial caregiving, predominantly undertaken by female relatives, is the primary form of support provided to patients with ADRD. Cultural stigma around dementia and limited access to support services amplify caregivers' challenges. This study examined psychological distress, depression, and quality of life (QoL) among family caregivers of patients with ADRD in Wakiso District, Uganda. METHODS: This cross-sectional study involved 90 caregivers from three sub-counties in Wakiso, selected through purposive sampling to capture diverse experiences. Participants included caregivers aged 18 years and older who were knowledgeable and had cared for a person with ADRD for not less than six months, with those providing more than 70% of physical care being prioritised. Data were collected using the Kessler Psychological Distress Scale, the Caregiver Dementia Quality of Life Measurement Scale, and the Center for Epidemiologic Studies Depression Scale, with an 80% response rate achieved through local collaboration. The statistical analyses focused on psychological distress, QoL, and depression. RESULTS: The study included 82.2% females and 17.8% males, with a median age of 52 years for females and 35 years, respectively. Females were more likely to be single or widowed, whereas males were more likely to be married. The study revealed a high prevalence of psychological distress and depression among caregivers (64.4%) regardless of sex. The analysis indicated that having children was a significant predictor of better QoL (OR 3.04, 95% CI 1.79-5.66, p = 0.034) and a lower risk of depression (OR 0.10, 95% CI 0.01-0.86, p = 0.036). No other sociodemographic factors were significantly associated with health outcomes across the models. CONCLUSION: Our findings revealed a heavy burden of psychological distress and depression among Ugandan caregivers of patients with ADRD, highlighting the need for structured support systems, including mental health services and gender-responsive interventions in low-resource settings.

Sex, environment, and death rate in a dementia cohort: a seven-years Bayesian survival analysis using medications data from a contaminated area in Italy.

Introduction: Studies have analyzed the effects of industrial installations on the environment and human health in Taranto, Southern Italy. Literature documented associations between different variables and dementia mortality among both women and men. The present study aims to investigate the associations between sex, environment, age, disease duration, pandemic years, anti-dementia drugs, and death rate. Methods: Data from the regional medication registry were used. All women and men with an anti-dementia medication between 2015 and 2021 were included and followed-up to 2021. Bayesian mixed effects logistic and Cox regression models with time varying exposures were fitted using integrated nested Laplace approximations and adjusting for patients and therapy characteristics. Results: A total of 7,961 person-years were observed. Variables associated with lower prevalence of acetylcholinesterase inhibitors (AChEIs) medication were male sex (OR 0.63, 95% CrI 0.42-0.96), age 70-79 years (OR 0.17, 95% CrI 0.06-0.47) and ≥ 80 years (OR 0.08, 95% CrI 0.03-0.23), disease duration of 2-3 years (OR 0.43, 95% CrI 0.32-0.56) and 4-6 years (OR 0.21, 95% CrI 0.13-0.33), and pandemic years 2020 (OR 0.50, 95% CrI 0.37-0.67) and 2021 (OR 0.47, 95% CrI 0.33-0.65). Variables associated with higher mortality were male sex (HR 2.14, 95% CrI 1.75-2.62), residence in the contaminated site of national interest (SIN) (HR 1.25, 95% CrI 1.02-1.53), age ≥ 80 years (HR 6.06, 95% CrI 1.94-18.95), disease duration of 1 year (HR 1.50, 95% CrI 1.12-2.01), 2-3 years (HR 1.90, 95% CrI 1.45-2.48) and 4-6 years (HR 2.21, 95% CrI 1.60-3.07), and pandemic years 2020 (HR 1.38, 95% CrI 1.06-1.80) and 2021 (HR 1.56, 95% CrI 1.21-2.02). Variables associated with lower mortality were therapy with AChEIs alone (HR 0.69, 95% CrI 0.56-0.86) and in combination with memantine (HR 0.54, 95% CrI 0.37-0.81). Discussion: Male sex, age, disease duration, and pandemic years appeared to be associated with lower AChEIs medications. Male sex, residence in the SIN of Taranto, age, disease duration, and pandemic years seemed to be associated with an increased death rate, while AChEIs medication seemed to be associated with improved survival rate.

Neurocognitive Disorders: Medical Illness or Mental Disorder: Examining the Mental Health and Wellbeing Act 2022 (Vic) Using Neurocognitive Disorders.

Victoria has new legislation, the Mental Health and Wellbeing Act 2022 (Vic) (MHWA) to govern the care and treatment of people with mental illness that came into effect on 1 September 2023. It takes a human rights approach with a focus on person-centred care. The definition of mental illness encompasses conditions such as dementia even though it is rarely used to manage such conditions. How would the management of dementia and associated conditions change if these conditions were managed under the MHWA? This article uses dementia to examine the differences between the new MHWA, the Medical Treatment Planning and Decisions Act 2016 (Vic) and the Guardianship and Administration Act 2019 (Vic) and how the human rights approach taken by the MHWA might inform future directions in managing dementia.

Denial of Desire for Death in Dementia: Why Is Dementia Excluded from Australian Voluntary Assisted Dying Legislation?

Euthanasia in the form of Voluntary Assisted Dying (VAD) is legal in all Australian States, but current eligibility criteria preclude access to people with dementia. This article discusses Australian VAD eligibility criteria that are problematic for people with dementia: (1) time until death within 12 months, (2) decision-making capacity for VAD, and (3) determination of intolerable suffering. Legislation in the Netherlands allows VAD for people with dementia. The challenges and philosophical issues raised by such cases are explored. It is proposed that the unique nature of dementia in its various forms warrants the formulation of dementia-specific VAD eligibility criteria. A case could be brought to challenge the denial of access to VAD of people with dementia on the basis that their exclusion is discriminatory and an abuse of human rights. If such a challenge was successful, it could form a common law precedent to allow people with dementia access to VAD.

A Systematic Review of Falls Risk of Frail Patients with Dementia in Hospital: Progress, Challenges, and Recommendations.

This review article assesses the effectiveness and limitations of strategies to reduce falls among hospitalized older adults with frailty and dementia. It explores the efficacy of existing fall prevention strategies for a cohort that is acutely susceptible to falls and fall-related consequences. A systematic literature search was conducted across MEDLINE, Embase, CINAHL, and PsycINFO, employing Medical Subject Headings (MeSH) to identify studies on fall prevention strategies in hospitalized older adults with both dementia and frailty published from 2013 to 2023. The initial 643 records were distilled to eight articles, with Structured Interdisciplinary Bedside Rounds (SIBR) emerging as a notable intervention. SIBR demonstrated a reduction in falls by fostering improved interdisciplinary communication and care planning. However, a decline in family engagement during consecutive sessions suggests a need for strategies to sustain familial involvement. The findings advocate for patient-centered interventions that address the cognitive and functional challenges faced by this cohort of older adults. This review advocates for comprehensive and inclusive research in hospital environments to improve fall prevention strategies for frail older adults with dementia.

Person-centredness in dementia care: an integrative review of theoretical approaches.

OBJECTIVES: This review identifies and examines theoretical approaches (components and objectives) to person-centred dementia care in order to obtain a better understanding of what is meant by the concept of person-centred dementia care. DESIGN: Following the approach of Whittemore and Knafl, an integrative literature review was conducted to answer the following questions: (1) Which theoretical approaches to person-centred dementia care have been published? (2) What are the components of the theoretical approaches to person-centred dementia care thus identified, and which objectives can be identified? DATA SOURCES: MEDLINE (via PubMed), CINAHL (via EBSCO) and PsycINFO (via EBSCO) were searched through to 26 April 2021. ELIGIBILITY CRITERIA: We included any kind of published literature that describes theoretical approaches to person-centred dementia care and that was written in German or English. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data. Data were pooled using a data extraction form developed by the Joanna Briggs Institute. A qualitative content analysis was conducted. RESULTS: The analysis revealed heterogeneous perspectives within the identified approaches to person-centred dementia care. Statements pertaining to the components and objectives could be assigned to three different subcategories (microlevel, macrolevel and application level). This analysis enabled an enhanced understanding of how person-centred dementia care is currently described and whether and how the theoretical approaches differ in terms of their orientations and their focus on the individual and/or on sociality, which allows conclusions regarding the underlying conceptual idea of personhood. CONCLUSIONS: There is a clear challenge for future research to overcome the dominance of the focus on the individual and to consider aspects of sociality to be at least equally important. This is needed in order to understand dementia as a multifaceted phenomenon that demands a differentiated consideration of theoretical notions of how to understand personhood in this context.

Analysis of eligibility criteria in Alzheimer's and related dementias clinical trials.

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.

Benzodiazepine use in relation to long-term dementia risk and imaging markers of neurodegeneration: a population-based study.

BACKGROUND: Benzodiazepine use is common, particularly in older adults. Benzodiazepines have well-established acute adverse effects on cognition, but long-term effects on neurodegeneration and dementia risk remain uncertain. METHODS: We included 5443 cognitively healthy (MMSE ≥ 26) participants from the population-based Rotterdam Study (57.4% women, mean age 70.6 years). Benzodiazepine use from 1991 until baseline (2005-2008) was derived from pharmacy dispensing records, from which we determined drug type and cumulative dose. Benzodiazepine use was defined as prescription of anxiolytics (ATC-code: N05BA) or sedative-hypnotics (ATC-code: N05CD) between inception of pharmacy records and study baseline. Cumulative dose was calculated as the sum of the defined daily doses for all prescriptions. We determined the association with dementia risk until 2020 using Cox regression. Among 4836 participants with repeated brain MRI, we further determined the association of benzodiazepine use with changes in neuroimaging markers using linear mixed models. RESULTS: Of all 5443 participants, 2697 (49.5%) had used benzodiazepines at any time in the 15 years preceding baseline, of whom 1263 (46.8%) used anxiolytics, 530 (19.7%) sedative-hypnotics, and 904 (33.5%) used both; 345 (12.8%) participants were still using at baseline assessment. During a mean follow-up of 11.2 years, 726 participants (13.3%) developed dementia. Overall, use of benzodiazepines was not associated with dementia risk compared to never use (HR [95% CI]: 1.06 [0.90-1.25]), irrespective of cumulative dose. Risk estimates were somewhat higher for any use of anxiolytics than for sedative-hypnotics (HR 1.17 [0.96-1.41] vs 0.92 [0.70-1.21]), with strongest associations for high cumulative dose of anxiolytics (HR [95% CI] 1.33 [1.04-1.71]). In imaging analyses, current use of benzodiazepine was associated cross-sectionally with lower brain volumes of the hippocampus, amygdala, and thalamus and longitudinally with accelerated volume loss of the hippocampus and to a lesser extent amygdala. However, imaging findings did not differ by type of benzodiazepines or cumulative dose. CONCLUSIONS: In this population-based sample of cognitively healthy adults, overall use of benzodiazepines was not associated with increased dementia risk, but potential class-dependent adverse effects and associations with subclinical markers of neurodegeneration may warrant further investigation.

Social Media Programs for Outreach and Recruitment Supporting Aging and Alzheimer Disease and Related Dementias Research: Longitudinal Descriptive Study.

BACKGROUND: Social media may be a useful method for research centers to deliver health messages, increase their visibility in the local community, and recruit study participants. Sharing examples of social media-based community outreach and educational programs, and evaluating their outcomes in this setting, is important for understanding whether these efforts have a measurable impact. OBJECTIVE: The aim of this study is to describe one center's social media activities for community education on topics related to aging, memory loss, and Alzheimer disease and related dementias, and provide metrics related to recruitment into clinical research studies. METHODS: Several social media platforms were used, including Facebook, X (formerly Twitter), and YouTube. Objective assessments quantified monthly, based on each platform's native dashboard, included the number of followers, number of posts, post reach and engagement, post impressions, and video views. The number of participants volunteering for research during this period was additionally tracked using a secure database. Educational material posted to social media most frequently included content developed by center staff, content from partner organizations, and news articles or resources featuring center researchers. Multiple educational programs were developed, including social media series, web-based talks, Twitter chats, and webinars. In more recent years, Facebook content was occasionally boosted to increase visibility in the local geographical region. RESULTS: Up to 4 years of page metrics demonstrated continuing growth in reaching social media audiences, as indicated by increases over time in the numbers of likes or followers on Facebook and X/Twitter and views of YouTube videos (growth trajectories). While Facebook reach and X/Twitter impression rates were reasonable, Facebook engagement rates were more modest. Months that included boosted Facebook posts resulted in a greater change in page followers and page likes, and higher reach and engagement rates (all P≤.002). Recruitment of participants into center-affiliated research studies increased during this time frame, particularly in response to boosted Facebook posts. CONCLUSIONS: These data demonstrate that social media activities can provide meaningful community educational opportunities focused on Alzheimer disease and related dementias and have a measurable impact on the recruitment of participants into research studies. Additionally, this study highlights the importance of tracking outreach program outcomes for evaluating return on investment.

Exploratory Mass Spectrometry of Cerebrospinal Fluid from Persons with Autopsy-Confirmed LATE-NC.

Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management. Participants (n = 29) had been autopsied and had antemortem CSF draws in a longitudinal cohort of older adults at the University of Kentucky AD Research Center. Cases were designated as LATE-NC + if they had LATE-NC stage > 1 (n = 9); the remaining 20 cases were designated LATE-NC-. This convenience sample of CSF specimens was analyzed in two separate processes: From one group, aliquots were depleted of highly abundant proteins using affinity spin columns. Tryptic digests of sample proteins were subjected to liquid chromatographic separation and mass spectrometry. Relative quantification was performed using Sciex software. Peptides referent to a total of 949 proteins were identified in the samples depleted of abundant proteins, and 820 different proteins were identified in the non-depleted samples. When the Bonferroni/false-discovery statistical correction was applied to account for having made multiple comparison tests, only 4 proteins showed differential expression (LATE-NC + vs LATE-NC-) in the non-depleted samples (RBP4, MIF, IGHG3, and ITM2B). Post hoc western blots confirmed that RBP4 expression was higher in the LATE-NC + cases at the group level. In summary, an exploratory assessment of proteomes of autopsy-confirmed LATE-NC and non-LATE-NC CSF did not demonstrate a clear-cut proteomic fingerprint that distinguished the two groups. There was, however, an increase in RBP4 protein levels in CSF from LATE-NC cases.

Vitamin B12 and Age-Related Cognitive Decline-Dementia and "Alzheimer's Disease".

This article is a commentary on the role of vitamin B12 in age-related cognitive decline, with a meta-commentary on the misuse of the term "Alzheimer's Disease." The article describes the historical origins of the term "Alzheimer's Disease" and argues that the term should be restricted to a narrower segment of the age-related dementia spectrum. The article also outlines the role of vitamin B12 in age-related cognitive decline and outlines the rationale for the treatment of B12 deficiency to address a potentially reversible factor in cognitive decline.

Subjective cognitive concerns, APOE ε4, PTSD symptoms, and risk for dementia among older veterans.

BACKGROUND: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with self-reported problems with cognition as well as risk for Alzheimer's disease and related dementias (ADRD). Overlapping symptom profiles observed in cognitive disorders, psychiatric disorders, and environmental exposures (e.g., head injury) can complicate the detection of early signs of ADRD. The interplay between PTSD, head injury, subjective (self-reported) cognitive concerns and genetic risk for ADRD is also not well understood, particularly in diverse ancestry groups. METHODS: Using data from the U.S. Department of Veterans Affairs (VA) Million Veteran Program (MVP), we examined the relationship between dementia risk factors (APOE ε4, PTSD, TBI) and subjective cognitive concerns (SCC) measured in individuals of European (n = 140,921), African (n = 15,788), and Hispanic (n = 8,064) ancestry (EA, AA, and HA, respectively). We then used data from the VA electronic medical record to perform a retrospective survival analysis evaluating PTSD, TBI, APOE ε4, and SCC and their associations with risk of conversion to ADRD in Veterans aged 65 and older. RESULTS: PTSD symptoms (B = 0.50-0.52, p < 1E-250) and probable TBI (B = 0.05-0.19, p = 1.51E-07 - 0.002) were positively associated with SCC across all three ancestry groups. APOE ε4 was associated with greater SCC in EA Veterans aged 65 and older (B = 0.037, p = 1.88E-12). Results of Cox models indicated that PTSD symptoms (hazard ratio [HR] = 1.13-1.21), APOE ε4 (HR = 1.73-2.05) and SCC (HR = 1.18-1.37) were positively associated with risk for ADRD across all three ancestry groups. In the EA group, probable TBI also contributed to increased risk of ADRD (HR = 1.18). CONCLUSIONS: The findings underscore the value of SCC as an indicator of ADRD risk in Veterans 65 and older when considered in conjunction with other influential genetic, clinical, and demographic risk factors.