bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term exposure to non‐steroidal anti‐inflammatory (NSAID) medication in relation to dementia risk: a population‐based cohort study
Authors: vom Hofe Ilse , Stricker Bruno H. , Ikram M. Kamran , Wolters Frank J. , Ikram M. Arfan
Published: January 2025

Background

Non‐steroidal anti‐inflammatory (NSAID) medication are suggested to have beneficial effects in the prevention of Alzheimer’s disease, due to anti‐inflammatory and possibly amyloid‐lowering properties. However, the results of observational studies and randomized‐controlled trials have been inconsistent, and duration and dose‐response relationships are still unclear.

Method

We included 11,745 dementia‐free participants from the prospective population‐based Rotterdam Study (59.5% women, mean age 66.2 years). NSAID use from 1991 was derived from pharmacy dispensing records, from which we determined cumulative duration and dose. We defined four mutually exclusive categories of cumulative use: non‐use, short‐term use (<1 month), intermediate‐term use (between 1‐24 months), and long‐term use (>24 months). We determined the association with dementia risk until 2020 using Cox regression models, including NSAID use as time‐varying exposure. Models were adjusted for lifestyle factors, comorbidity and comedication use. We repeated the analyses stratified by previously established amyloid‐lowering properties of different NSAIDs.

Result

During an average follow‐up period of 14.5 years, a total of 9,520 (81.1%) participants had used NSAIDs at any given time, and 2,091 participants developed dementia. Use of NSAIDs was associated with lower dementia risk for long‐term users (hazard ratio (HR) [95%CI]: 0.88[0.84;0.91]), but not with short‐term use (HR[95%CI]: 1.04[1.02;1.07]) or intermediate term use (HR[95%CI]: 1.04[1.02;1.06]). The cumulative dose of NSAIDs was not associated with decreased dementia risk (HR[95%CI] for <25th percentile: 1.06[1.03;1.09], 25‐50th percentile: 1.02[0.99;1.05], 51‐75th percentile: 1.03[0.99;1.06], >75th percentile: 0.99[0.96;1.02]). Associations were somewhat stronger for NSAIDs without known effects on amyloid than for amyloid‐lowering NSAIDs (HR[95%CI]: 0.79[0.74;0.85] versus 0.89[0.85;0.93]).

Conclusion

Long‐term NSAID use, but not cumulative dose, was associated with decreased dementia risk. This suggests that prolonged rather than intensive exposure to anti‐inflammatory medication may hold potential for dementia prevention.
Reasons for screening failure in the evoke and evoke+ trials of semaglutide for early AD
Authors: Sano Mary , Cummings Jeffrey L. , Feldman Howard H. , Hansson Oskar , van der Flier Wiesje M. , Bardtrum Lars , Jeppesen Rose , Johannsen Peter , Léon Teresa , Hansen Charlotte T. , Scheltens Philip
Published: January 2025

Background

Alzheimer’s disease (AD) trials report a high screening failure rate (potentially eligible trial candidates who do not meet inclusion/exclusion criteria during screening) due to multiple factors including stringent eligibility criteria. Here, we report the main reasons for screening failure in the 12‐week screening phase of the ongoing evoke (NCT04777396) and evoke+ (NCT04777409) trials of semaglutide in early AD.

Method

Key inclusion criteria were age 55‐85 years; mild cognitive impairment due to AD (Clinical Dementia Rating [CDR] global score of 0.5 plus CDR of ≥0.5 in ≥1 of three activities of daily living categories) or mild AD dementia (CDR global score of 1.0); Repeatable Battery for the Assessment of Neuropsychological Status delayed memory index (RBANS‐DMI) score ≤85; Mini‐Mental State Examination (MMSE) score ≥22; amyloid positivity (confirmed by positron emission tomography or cerebrospinal fluid). Additionally, evoke+ allowed the inclusion of participants with significant small vessel pathology (>1 lacunar infarct and/or age‐related white matter changes >2 [white matter >20 mm]). Among the exclusion criteria were evidence of neurological disorders other than AD; evidence of a clinically relevant or unstable psychiatric disorder; magnetic resonance imaging (MRI)/computerized tomography (CT) scan suggestive of clinically significant structural central nervous system (CNS) disease (other than the changes allowed for evoke+) nor suggestive of strategic infarcts. Screening failure rates were summarized descriptively. Data cleaning of the 3806 randomized individuals is ongoing in evoke/evoke+.

Result

The total number of screening failures was 2,836 (58.6%) in evoke and 3,087 (59.8%) in evoke+. The top five categories of screening failure in evoke and evoke+ were RBANS‐DMI score ≤85, MMSE score ≥22, amyloid positivity, CDR score, and MRI/CT scan suggestive of CNS disease (other than the changes allowed for evoke+) or strategic infarcts (Figure). This reflected the hierarchical procedure applied during screening, whereby individuals were firstly assessed on cognitive scores, followed by exclusion of other neurological disorders and, lastly, confirmation of amyloid positivity.

Conclusion

The hierarchical screening procedure in evoke and evoke+ resulted in most ineligible patients being excluded early in the screening process. The main reasons for screen failure were cognitive assessment scores.
Changes in cerebrospinal fluid synaptic proteins precede and coincide with Alzheimer’s pathology and govern cognitive function
Authors: Oh Hamilton Se‐Hwee , Wyss‐Coray Tony
Published: January 2025

Background

The buildup of brain amyloid‐beta and tau protein aggregates do not sufficiently explain the heterogeneity in cognitive impairment in Alzheimer’s disease (AD).

Method

To elucidate drivers of cognitive impairment, we measure the levels of 7,000 proteins, in addition to amyloid‐beta‐42 (Ab42) and phospho‐tau‐181 (PTau181), from the cerebrospinal fluid of 2,000 individuals from healthy to severe dementia.

Result

We identify synapse proteins as the strongest correlates of cognitive impairment. We use machine learning methods to derive a cognitive impairment signature, provided as the ratio between YWHAG and NPTX2, which increases with impairment severity (r=0.57) and explains resilience versus susceptibility to AD pathology. We find YWHAG:NPTX2 also increases with age in healthy individuals before PTau181:AB42 and increases 25 years before symptom onset (as early as PTau181:AB42) in autosomal dominant AD.

Conclusion

Our work reveals that synapse alterations precede and coincide with AD pathology accumulation and are the arbiters of cognitive decline. Additionally, we propose the CSF YWHAG:NPTX2 ratio as a biomarker for monitoring synapse health and predicting future cognitive decline in living people.
Effect of dietary habits on Alzheimer’s disease progression
Authors: Choi Seong Hye , Jeong Jee Hyang , Minn Yangki
Published: January 2025

Background

Research on the relationship between diet and dementia among Koreans are lacking. This study investigated the association between dietary habits and dementia progression over 3 years in patients with Alzheimer’s disease dementia (ADD).

Method

This study included 705 patients with mild‐to‐moderate ADD. Dietary habits were assessed using the Mini Dietary Assessment Index, comprising 10 questions. Outcome measures included the Clinical Dementia Rating scale‐Sum of Boxes (CDR‐SB), Seoul‐Instrumental Activities of Daily Living, Caregiver‐Administered Neuropsychiatric Inventory (CGA‐NPI), and neuropsychological test battery (NTB) z‐scores, which were evaluated annually over 3 years.

Result

In Q10 (eat all food evenly without being picky), the 3‐year mean differences in CDR‐SB (increases in scores represent worsening) compared to the “rarely” group were –1.86 (95% confidence interval [CI] = –3.64 ∼ –0.09, P = 0.039) for the “usually” group and –2.23 (95% CI = –4.40 ∼ –0.06, P = 0.044) for the “always” group. In Q7 (add salt or soy sauce to food, when eating), the 3‐year mean differences in CDR‐SB compared to the “always” group were –2.47 (95% CI = –4.70 ∼ –0.24, P = 0.030) for the “usually” group and –3.16 (95% CI = –5.36 ∼ –0.96, P = 0.005) for the “rarely” group. The “rarely” and “usually” groups in Q7 showed significantly less decline in NTB z‐score and CGA‐NPI compared to the “always” group.

Conclusion

Eating a balanced diet and reducing salt intake were associated with a slower decline in dementia severity, cognition, and behavioral alterations in patients with ADD.
Dental caries, dental hygiene and selfcare, and use of dental health services, and risk of cognitive decline – an 11‐year follow‐up cohort study
Authors: Asher Sam , Suominen Anna Liisa , Stephen Ruth , Ngandu Tiia , Koskinen Seppo , Solomon Alina
Published: January 2025

Background

Current evidence links poor oral health, especially tooth loss, with impaired cognition. However, role of underlying causes of tooth loss e.g., dental caries is not known. Moreover, concerning cognition, impact of dental hygiene and selfcare, and use of dental health services is yet to be studied. This study assesses various dental‐health related variables against 11‐year cognitive decline.

Method

Study included ≥30 years old individuals (N = 2958) who participated in the Finnish Health 2000 and its follow‐up Health 2011 Surveys. Dental caries for all teeth (except third molars) and dental hygiene or presence of plaque at 3 teeth/sites were clinically assessed at baseline (2000). Dental selfcare was assessed through daily brushing frequency, and number of visits to dental healthcare professionals in past 12 months indicated use of dental health services. Cognitive assessment at baseline (2000) and follow‐up (2011) was done via cognitive test battery including verbal fluency, immediate and delayed word recall. To assess overall cognition, a composite cognitive score was calculated both at baseline and follow‐up as a sum of individual cognitive tests. For each cognitive test, including composite cognitive score, 11‐year cognitive decline was calculated as difference between scores in 2011 and 2000. Exposure‐Outcome associations were analyzed via binary logistic regression and adjusted for multiple relevant covariates.

Result

After adjustments poor oral hygiene demonstrated by having plaque at ≥2 teeth was associated with decline in verbal fluency and delayed recall. Inadequate dental selfcare demonstrated by brushing <1 times daily and extensive use of dental health services demonstrated by ≥2 visits to different dental healthcare professionals in the past 12 months were both associated with decline in total immediate recall. However, no association for dental caries was observed.

Conclusion

Preliminary results indicated higher risk of cognitive decline in individuals with poor oral hygiene, inadequate oral hygiene practices and recent history of multiple visits to dental healthcare facilities. In light of these findings, future studies into the factors influencing these modifiable patterns are recommended.
Neuroprotective Effect of Filgrastim against Rotenone induced Parkinson’s disease in Rats
Authors: Chaudhary Hema , Agrawal Mohit
Published: January 2025

Background

Parkinson’s disease is an hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid‐brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Filgrastim has been reported to produce anti‐oxidant, anti‐inflammatory and neuromodulatory actions in previous studies.

Method

In the current study we have investigated the role of filgrastim against rotenone induced motor deficit and biochemical abnormalities in Wistar rats. Rats were treated with 1.5mg/kg rotenone subcutaneously for 35 days. filgrastim (50,100 and 200 mg/kg i.p.) was administered after 30 minutes of rotenone administration from day 7th to 35th day. Rotenone caused significant reduction in motor functions and body weight and produced elevation in striatal oxidative burden. The biochemical analysis revealed that there is reduction in the level of anti‐oxidants (GSH, Catalase, and SOD) in the animals following rotenone administration.

Result

Whereas filgrastim treated rats were stable and regained their body weight. In addition filgrastim significantly attenuated rotenone induced motor deficit and striatal oxidative stress.

Conclusion

Outcomes of the current study suggest neuroprotective potential of filgrastim and its ability to correct movement disability and thus could prove to be useful candidate molecule in the management of motor disorders.
Implementing a Dementia‐Friendly Communities programme across local authorities in the East of England
Authors: Windle Greg
Published: January 2025

There are many types of Dementia‐Friendly Communities (DFCs), and communities define and implement them in different ways. Toolkits from the World Health Organisation and Dementia Friendly America have defined specific goals for DFCs, and in 2013, Alzheimer’s Society created a national recognition programme for UK DFCs to respond to the diversity of interpretations. Key elements of the programme included People (awareness and training), Process (support and signposting) and Place (physical support and community). The complex implementation of DFCs in diverse regions has not been extensively studied, and the Alzheimer’s Society DFC accreditation programme for England ended in 2023.

In order to keep continuity, regional governments in England are developing their own frameworks for implementing DFCs. County‐level local governments have convened a number of district councils to agree to continue with a DFC scheme in 2024 as a key part of the delivery of the county‐level dementia strategy for 2023 through 2028. This dementia strategy covers a broad range of community concerns, but it does not consider detailed implementation questions. A task force made up of local government officials, clinical commissioning group representatives, admiral nursing representatives, care home leaders and voluntary organisation heads is developing and implementing the new DFC programme. The continued DFC programme takes a federal structure, with a county‐wide set of criteria for defining levels of dementia‐friendly services in the community. Each local government within the county then has flexibility to tailor the criteria to their own population, business and service landscape.

As DFCs in the East of England adjust to this new administrative framework, we are using an evaluation and implementation framework to measure individual and community impact and describe implementation consideration for this method of DFC administration. The main focus of implementation science has been in clinical practice, but there is a growing focus on the importance of evidence‐based public policies and their implementation. In detailing the implementation of this innovative community care programme, we consider implementation domains of Contextual Factors, Implementation Strategies, Service and Patient Outcomes, Implementation Outcomes, Economic Evaluation, Stakeholder Involvement and Engagement and Patient and Public Involvement and Engagement.
Long‐term impact of COVID‐19 infection on cognitive dysfunction among Chinese older adults: a national cross‐sectional online study
Authors: Huang Qing , Wu Jingnan , Li Liming , Yao Shi , Wang Yan , Li Yatian , Cui Lili
Published: January 2025

Background

The effects of the SARS‐CoV‐2 virus (COVID‐19) on the central nervous system predispose to cognitive dysfunction in older adults. However, limited information is available on how long this impact will last. This study aims to assess the cognitive decline in Chinese older adults after COVID‐19 using a cross‐sectional study.

Method

A nationwide cross‐sectional study was conducted among 1698 individuals over 50 years old who completed an online questionnaire survey on their cognitive impairment. Based on the Subjective Cognitive Decline Questionnaire (SCD‐Q), we designed a self‐administration SCD‐18 questionnaire that assess perceived subjective decline in attention, comprehension, memory, emotion, motivation and sleep. The scores of each evaluation index in the SCD‐18 questionnaire ranges from 0 to 6, with higher scores indicating a greater possibility of cognitive dysfunction. We compared differences in relevant cognitive function between different participants and performed a multiple linear regression analysis to identify factors that might be associated with cognitive function.

Result

Older adults who were infected with COVID‐19 had significantly higher SCD‐18 scores than uninfected participants (P = 0.005). Among the infected participants, the SCD‐18 scores of females were significantly higher than that of males (P = 0.007), especially in memory (P<0.001), and rural participants had higher SCD‐18 scores than urban participants (P<0.001). Specifically, the SCD‐18 scores of the infected participants for 1‐6 months were significantly higher than that of the uninfected participants (P = 0.003), especially in comprehension (P = 0.011), memory (P<0.001), motivation (P = 0.016), and sleep (P = 0.008). Participants infected for more than 6 months did not have significantly different SCD‐18 scores from uninfected participants (P = 0.118), suggesting that cognitive function gradually recovered. Regression analysis indicated that female and rural area were associated with cognitive impairment.

Conclusion

The cognitive function of older adults due to the COVID‐19 pandemic has changed over time. Female and rural area were the risk factors for cognitive decline. Therefore, further long‐term interventions for vulnerable older adults with a history of COVID‐19 should be considered to maintain cognitive health.
Loneliness among people living with dementia: results from the English Longitudinal Study of Ageing
Authors: Tapia‐Muñoz Thamara , Miranda‐Castillo Claudia
Published: January 2025

Background

Literature often focuses on loneliness as a risk factor for dementia. However, loneliness among those living with dementia (PLWD) is yet to be further explored.

Method

Secondary analysis of the English Longitudinal Study of Ageing. Across ELSA waves 1 to 9, we identified 181 participants who reported being diagnosed with dementia and randomly selected 775 (10%) non‐dementia participants (NDP) from wave 2 (2004‐2005). For PLWD, the baseline was the year they reported the diagnosis. For NDP, the baseline was information from waves 1 and 2. We obtained a two‐year lagged loneliness for a subsample (n = 70 PLWD and n = 569 NDP). We computed multiple linear regression models using bootstrap errors with 1000 iterations to describe the average levels of loneliness among people living with dementia in England.

Result

Both groups did not differ in their socioeconomic characteristics except for age. PLWD were, on average, 76 years old (Sd = 9.74), and NDP was 66 years old (sd = 9.53). The average level of loneliness was 4.71 (sd = 1.74) for PLWD and 4.07 (sd = 1.47) for NDP. At baseline, the loneliness prevalence was 15.76% among PLWD and 7.55% for NDP. Among PLWD, the average 2‐year lagged loneliness was 4.72 (sd = 1.79), and 21% reported problematic loneliness, and among NDP, it was 4.18 (sd = 1.52) and 10%, respectively. Adjusted baseline levels of loneliness were statistically significantly higher among PLWD (Coef. = 0.694; 95% CI: 0.393‐0.994). For the 2‐year lagged loneliness, dementia and non‐dementia participants did not significantly differ in their levels of loneliness.

Conclusion

Public policies should consider tackling loneliness among people living with dementia.
Alzheimer’s Disease Prediction and Implications for Insurance
Authors: Wittrock Julia , Schmitz‐Luhn Björn
Published: January 2025

Background

The possibilities to determine the individual risk of persons to develop future Alzheimer’s Disease and dementia have greatly increased in recent years. Promising and little invasive methods, e.g. blood or urine tests, may soon be available as predictive or early‐detection measures even for the general population. However, the knowledge incurred may be of interest not only for the affected persons themselves, but also for third parties. Particularly, the results of predictive tests may prompt disclosure or notification obligations to insurers, in turn affecting availability or affordable premiums for life or health insurance plans. This can be a substantial obstacle and burden for individuals considering to undergo predictive diagnosis. As predictive methods become more readily available, the problem gains pressing practical importance.

Method

We analyze existing legislation and jurisprudence in a variety of jurisdictions to investigate what regulations are in place for dealing with individual risk probabilities, and to what extent these are applicable or transferable to the particular problematic aspects regarding the prediction of Alzheimer’s Disease and/or dementia.

Result

Existing insurance law, where in place, strikes only a rudimentary balance, and for a limited scope, mostly genetic diagnostics only. At the same time, access to disease prediction by non‐genetic means is quickly growing, and legal protections, rights and duties are largely unregulated in spite of a similar conflict of interests. The associated uncertainties for the involved parties keep increasing, and there is a pressing need for rules bringing the conflicting interests into a fair balance.

Conclusion

We present efforts and their shortcomings to reduce the tension between the interest of insurers in offering affordable and calculable premiums on the basis of individual risk factors, and the particular need of affected persons to protect the results of predictive examinations due to their high sensitivity. We show how this tension could be sensibly resolved by taking into account ethical and societal values, considering the complex interests at stake.
Health Literacy, Blood Pressure Variability, and Domain‐specific Cognitive Changes
Authors: Ihara Keiko , Opsasnick Lauren , Bonham Morgan , Batio Stephanie , Yoshino‐Benavente Julia , Curtis Laura M , Bailey Stacy C , Wolf Michael S , Kim Minjee
Published: January 2025

Background

Both limited health literacy (HL) and elevated blood pressure variability (BPV) in later life have been associated with the risk of dementia and cognitive impairment. However, little is known about the relationship between HL, BPV, and domain‐specific cognitive decline. We aimed to examine this relationship among primary care older adults.

Method

English‐speaking adults aged 55‐74 were recruited from an academic general internal medicine practice and federally qualified health centers in Chicago between 8/2008 and 6/2010. HL was measured by the Newest Vital Sign. BPV was assessed by variation independent of mean systolic blood pressure calculated from all blood pressure measures obtained during routine ambulatory visits that occurred in calendar years 2008 – 2012. Five cognitive domains (processing speed, inductive reasoning, and working, long‐term, and prospective memories) were assessed through 15 tests at baseline, which were repeated three additional times at a 2.5‐year interval. Changes in Z‐scores were calculated from baseline (T1) to the last available assessment (T4 or T3) for each of the five cognitive domains. We examined associations between BPV and domain‐specific cognitive changes with univariate and multivariable regression, adjusting for a priori covariates including baseline age, sex, race, hypertension, number of chronic conditions excluding hypertension, cognitive function, HL, and interval between cognitive assessments.

Result

A total of 299 participants (age 63.3 ± 5.3; 73% female; 26% non‐Hispanic Black, 67% non‐Hispanic White; 1.8 ± 1.3 chronic conditions; 51.8% with hypertension at baseline) were included in analyses (Table 1). Median interval between cognitive assessments was 8.4 years (IQR 8.2‐8.7). Baseline hypertension (β, 1.00; 95% confidence interval (CI), 0.28‐1.71; p = 0.006) and limited HL (β, 1.42; CI, 0.65‐2.20; p<0.001) were significant predictors of 5‐year BPV (Table 2). Greater 5‐year BPV was significantly associated with decline in long‐term memory (β, ‐0.035; CI, (‐0.064)‐(‐0.007); p = 0.016), but not with changes in other cognitive domains, after adjusting for a priori covariates (Table 3).

Conclusion

Limited health literacy in later life is associated with greater variability of systolic blood pressure over five years, which was, in turn, associated with greater decline in long‐term memory over a median follow‐up of eight years.
Towards a sole β‐amyloid‐centered definition of Alzheimer’s disease? Risks and alternatives
Authors: Villain Nicolas , Hanseeuw Bernard J , Planche Vincent
Published: January 2025

Aims

The Alzheimer Association (AA) has proposed new diagnostic criteria for Alzheimer’s disease (AD) based on biomarkers coinciding with β‐amyloidosis onset. However, there are concerns regarding the implications of these criteria.

Methods

We reviewed several perspectives, including disease definition, public health, philosophy, therapeutic, and diagnostic.

Results

1. Disease definition – the AA definition displays limited and heterogeneous predictive capabilities of lifetime clinical progression in asymptomatic individuals, and a different disease label may be used, as seen in other examples in medicine (eg MGUS and multiple myeloma).

2. Public health – the majority of the A+ population is asymptomatic, and the AA definition may reduce the association between the “label” AD and dementia or subsequent progression to dementia, which could impact public health decisions.

3. Philosophy – the clinical and biological definitions of AD are based on different medical‐philosophical theories of disease (Nordenfelt vs. Boorse), and if the AA criteria are widely adopted, there may be misconstrued perceptions among stakeholders.

4. Therapeutic – an amyloid definition of AD disconnects the biological endpoint from the clinically relevant outcome, which has led to the approval of aducanumab without demonstrating clinical impact. This raises concerns about future decisions regarding asymptomatic individuals.

5. Diagnostic – the AA framework lacks clear guidelines on linking clinical situations with AD biological changes, which may result in misdiagnosis and overdiagnosis in patients with abnormal biomarkers.

Conclusions

Defining AD based solely on β‐amyloidosis is risky and reduces association with clinically relevant outcomes. Diagnosing AD should instead involve symptoms or a high probability of developing them. The IWG framework takes a cautious approach, focusing on symptom onset. Future IWG developments could expand the “preclinical AD” label by integrating specific biomarkers that can predict severe cognitive decline in asymptomatic patients.
RWD insights into the global cost of Alzheimer’s and dementia
Authors: Jönsson Linus
Published: January 2025

It is well recognised that Alzheimer’s disease and related dementia disorders (ADRD) are associated with very high societal costs. The total global costs of dementia have been estimated to over 1.3 trillion US$ annually (Wimo, Seeher et al. 2023). Real‐world data (RWD) sources such as national patient registers, claims databases, disease and quality of care registers, offer an opportunity to assess resource utilisation and cost, as they reflect routine clinical practice in representative patient populations. However, as the majority of the costs of dementia fall outside of the health care system, most RWD sources offer only a partial view of the costs of dementia. Globally, only about 16% of costs are health‐care related, while 34% are related to social care and 50% are attributed to informal care (Wimo, Seeher et al. 2023). Most RWD sources specific for ADRD do not collect data on resource utilization or costs, though some offer opportunities for record linkage with databases containing such data. Therefore, most knowledge about costs of dementia has been derived from smaller observational studies with the specific purpose of assessing costs of care (Jonsson, Tate et al. 2023).

New methods for diagnosing and treating ADRD are being introduced, including amyloid‐targeting antibody therapies and blood biomarkers. RWD will play a key role in ensuring the appropriate and cost‐effective use of these technologies. To assess the cost implications of introducing these technologies in routine care, disease registries and other RWD sources need to be expanded to include key measures of resource utilization, including informal care and community care services.
Cognitive Impairment in Firefighters and Emergency Medical Services Workers after Severe WTC Exposures
Authors: Mann Frank D
Published: January 2025

Background

Members of the Fire Department of New York (FDNY) who responded to the World Trade Center (WTC) attacks that occurred on 9/11/2001 were exposed to severe trauma. The present study screened for cognitive impairment in a prospective cohort study of FDNY fire fighters and emergency personnel who reside in the greater NYC metropolitan area.

Method

A large sample (n = 338) of FDNY personnel who were exposed to the WTC attacks were recruited to complete a large battery of neuropsychiatric and psychological tests. The Montreal Cognitive Assessment (MoCA) was used to screen for mild cognitive impairment (MCI) and probable dementia. Neuropsychiatric, psychological, and physical deficits were further characterized by the Short Physical Performance Battery (SPPB), Hopkins Verbal Learning Task (HVLT‐R), Boston Naming Task (BNT), Wide Range Achievement Test (WRAT‐4), Trail‐Making Task (TMT), Symbol Digit Modalities Test (SDMT), Controlled Oral Word Association (COWA), Patient Health Questionnaire (PHQ‐9), and the Cognitive Function Instrument (CFI). Diagnoses of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) were made using the Structural Clinical Interview for DSM‐5.

Result

Compared to the general population, prevalence of MCI (22.92%, CI.95 = [18.42%, 27.63%]) and probable dementia (4.14%, CI.95 = [2.28%, 6.85%]) were precipitously high. Compared to unimpaired firefighters, those with MCI and probable dementia exhibited statistically significant deficits (p‐values < .05) on the HVLT‐R, BNT, WRAT‐4, TMT, SDMT, and COWA, while differences on the SPPB, PHQ‐9, and CFI were not statistically significant (p‐values > .05). Prevalence of current PTSD (18.05%, CI.95 = [14.10, 22.57] and MDD (6.51%, CI.95 = [4.12%, 9.69%] were high and moderate, respectively, but not significantly associated with MCI or probable dementia (p‐values > .05).

Conclusion

There is a high prevalence of MCI and probable dementia among member of the FDNY who responded to the WTC attacks. The present study further highlights the role of extreme physical exposes in the pathogenesis of cognitive impairment and dementia. This group is a high priority for public health efforts and clinicians need to anticipate MCI and dementia in treatment planning.
Incidence of dementia before age 65 years following World Trade Center exposure: A prospective study of cognition in general responders
Authors: Clouston Sean A.P. , Team World Trade Center Aging Research
Published: January 2025

Background

The goal of this study was to determine the incidence of dementia before age 65 years in a prospective study of WTC responders, and compare incidence among responders with severe exposures to debris versus responders not exposed to building debris or those who wore personalized protective equipment (PPE).

Methods

Data were collected in a congressionally mandated academic occupation‐based medical monitoring program available to all verified WTC‐exposed responders residing on Long Island, NY, most of whom are currently <65 years of age. WTC responders aged ≤60 years without dementia at the time of their first cognitive assessment were followed every 18 months on average, for up to five years. We determined exposure severity based on responses to a detailed questionnaire of WTC‐related exposures and exposure‐related work activities that proxied exposures to fine particulate dust and potentially neurotoxic chemicals/dust/debris, duration of work, and the use PPE. We categorized exposure levels using an ordinal variable with five categories ranging from low to severe exposure. The incidence of dementia before age 65 years was the outcome, and was diagnosed following standard guidelines.

Results

Of 9,891 responders in the cohort, 5,010 were eligible for inclusion in this study of cognitive function (median age 53; 437 (8.72%) female), and there were 228 cases of dementia identified during 15,913.1 person‐years of follow‐up. Increasing severity and duration of exposure reported at the WTC sites revealed incremental increases in the incidence of dementia (Figure 1). After adjusting for social, demographic, and relevant medical factors, each unit increase in exposure severity was associated with increased incidence of dementia (risk difference = 39.42 [11.12‐139.70] P<0.001; hazards ratio = 1.42 [1.18–1.71], P<0.001).

Conclusions

Among WTC responders who survived to participate in a longitudinal follow‐up study of cognition from 2014‐22, a higher level of reported exposure to dust/debris, when compared with the lowest reported exposure levels or use of PPE, was significantly associated with a higher risk of dementia before age 65 years.
Early Adversity and Its Impact on Cardiovascular Health: Laying the Groundwork for Dementia Research
Authors: Wang Liang , Bauermeister Sarah
Published: January 2025

Background

Cardiovascular disease (CVD) and dementia share common risk factors like hypertension, diabetes, obesity, smoking, alcohol consumption, physical inactivity, and depression, indicating a complex interplay in their etiologies. This systematic review investigates the connections between early adversity (EA), such as low socioeconomic status (SES) and emotional abuse, and the development of CVD, focusing on how early‐life experiences contribute to CVD comorbidity, a crucial factor in the development of dementia.

Method

Following the PRISMA guidelines, we conducted a comprehensive literature search in databases including Medline, Embase, PsycINFO and Global Health, covering publications from 2000 to November 2023. The search focused on keywords relating to EA, CVD, and aging. Inclusion and exclusion criteria were applied, alongside the use of the QUIPS risk evaluation tool, to ensure rigorous analysis. The primary focus was on studies that explored long‐term cardiovascular outcomes in individuals exposed to EA.

Result

From a comprehensive analysis of 22 articles, we revealed a significant association between EA and critical CVD risk factors like abdominal obesity, smoking, and late‐life hypertension, which are potential causes of dementia. Early life factors, such as lower education levels and socioeconomic status, were found to significantly influence the risk of CVD and associated factors. These early life challenges affect not only physical health, leading to conditions like hypertension and diabetes, but also lifestyle choices related to smoking and alcohol use. Moreover, factors like reduced physical activity, depressive symptoms, and environmental elements such as air pollution were identified as contributing to the development of CVD risks. Collectively, these factors form pathways through which EA increases the likelihood of CVD and subsequent dementia.

Conclusion

This systematic review emphasizes the profound and enduring impact of early life adversities on key risk factors for cardiovascular disease. These insights highlight the need for early interventions and long‐term monitoring of individuals with adverse childhood experiences to reduce future CVD risk. Importantly, this research lays a pivotal foundation for future exploration into dementia risk factors, suggesting an important interrelationship between early adversity, cardiovascular disease and dementia.
MEG Biomarkers in relation to plasma neuropathology biomarkers of Alzheimer’s disease
Authors: García‐Colomo Alejandra
Published: January 2025

Background

The preclinical stage of Alzheimer’s disease (AD) has gained attention for the window of opportunity it opens for early detection and intervention. Given the high invasiveness of PET and CSF markers, electrophysiology and plasma biomarkers are being studied as alternate biomarkers for early detection and disease tracking. The aim of this study is twofold. First, to address the relationship between a compound centrality score (CS; i.e., a measure of the relevance of a region within the network) and plasma pathology markers of AD in unimpaired individuals with elevated neurofilament‐light chain (NfL) and phosphorylated tau 231 (p‐tau231). Lastly, to evaluate whether this association is greater in hubs.

Method

33 individuals with available MEG recordings and over‐the‐median plasma NfL and p‐tau231 levels were included. A compound CS for each 1210 brain sources of every subject was calculated combining classical centrality metrics. The association between each node’s CS and plasma biomarkers was studied using a correlation analysis. A subsequent correlation between the obtained rho and the grand‐average of the CS was performed to test whether greater associations were found in hubs.

Result

Increasing p‐tau231 concentrations were associated with greater relevance of posterior areas through their theta oscillations and lower relevance of left areas through their gamma oscillations. The most relevant areas are also the ones that present the greatest association between their CS and p‐tau231.

Conclusion

The results of this pioneering study are consistent with previous literature and demonstrate early alterations in network communication associated with elevated plasma biomarkers in cognitively unimpaired individuals, particularly in vulnerable areas to AD pathology.
High‐frequency oscillations in animal models of Alzheimer’s Disease
Authors: Lisgaras Christos
Published: January 2025

Background

Clinical and preclinical evidence suggest that abnormal electrical activity strongly impacts outcomes in Alzheimer's disease (AD). Indeed, AD patients with interictal spikes (IIS) show faster cognitive decline than those without IIS. Furthermore, seizures in patients with AD have been suggested to accelerate disease progression. Here we asked whether high‐frequency oscillations (HFOs), which for the last 20 years have been considered a promising electrophysiological biomarker in epilepsy, also occur in preclinical AD models.

Method

We used three mouse lines with AD features: Tg2576 mice, presenilin 2 knock‐out (PS2KO) mice, and the Ts65Dn model of Down's syndrome. We recorded HFOs using wideband (0.1–500 Hz, 2 kHz) intra‐hippocampal and cortical surface EEG at 1 month until 24 months of age during wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep. In addition, we analysed IIS and compared their occurrence with HFOs.

Result

HFOs occurred in all transgenic mice but no controls. They were also detectable as early as 1 month of age and prior to amyloid beta plaque neuropathology. HFOs were most frequent during SWS sleep (vs REM sleep or wakefulness) when patients with AD also show abnormal EEG. Notably, HFOs were more frequent than IIS and occurred during more behavioral states. Last, high numbers of HFOs correlated with fewer IIS, suggesting for the first time possible competing dynamics among them in AD.

Conclusion

Our data demonstrate that HFOs, an epilepsy biomarker with high translational value, occurs early during AD progression. Also, HFOs were the most abundant EEG abnormality when compared to IIS, and occurred in all behavioral states, suggesting they may become a promising surrogate marker of hyperexcitability in AD.
Using Podcasts as a Learning Tool to Decrease Stigma and Increase Awareness of the Experience of Dementia
Authors: Hickman Kathy
Published: January 2025

Dementia Dialogue is a podcast produced by the Alzheimer Society of Ontario that provides people with lived experience (people living with dementia and care partners) a way to share their stories with each other and the broader community. Listeners who have dementia and care partners gain insight and strengthen their adaptive skills. Listeners who work with people living with dementia and care partners as well as community members at large, develop an understanding of what it means to live with dementia and how these individuals can be supported, thereby increasing awareness about the experience of dementia and decreasing stigma.

A series of Learning Guides utilizing these podcasts have been created to help people with lived experience of dementia as well as others within the community, specifically professionals and volunteers supporting those with dementia and their care partners, to explore the various themes of the Dementia Journey. The Learning Guides describe key points along the dementia journey and use embedded podcast excerpts that demonstrate these themes. Excerpts are followed by reflection/discussion questions targeted to specific learner groups to aid formulation of ideas about what can be learned and how it can be applied in practice to one’s own experience. Learners can engage with the guides through independent self‐study or in group settings with a facilitator. Focus groups and surveys were conducted with people with lived experience, professionals/volunteers and educators to assess utility of the learning guides and explore the potential for development of elearning versions of the learning guides.

Delegates will learn about the podcast, learning guides and results from the testing of these.
Potential of targeting the alpha‐1 adrenergic receptor and phosphoglycerate kinase 1 with Terazosin to treat Alzheimer’s disease using a transgenic AD rat model
Authors: Pattanashetty Swastik G , Xie Lei , Serrano Peter , Rockwell Patricia , Figueiredo‐Pereira Maria
Published: January 2025

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder without a cure. Targeting this multifactorial disease by repurposing FDA approved drugs serves as a faster mode of treatment due to its pre‐established human safety. We tested terazosin (TZ), an a‐1 adrenergic receptor (AR) antagonist and phosphoglycerate kinase‐1 (PGK1) activator as having potential to treat AD. Early stage of AD is characterized with loss of noradrenergic neurons in the locus coeruleus (LC) that initiates an over compensatory mechanism leading to increased production of norepinephrine. This causes increased synaptic activity in LC thus increasing Ab deposition via endocytosis of APP. Furthermore, dysregulated glycolysis causing decreased ATP levels is shown to play a causal role in the progression of AD and PGK1 is the first ATP generating enzyme in glycolysis.

Hypothesis

TZ via its dual mechanism of action by blocking a‐1 AR and activating PGK1, will exert neuroprotective effects and ameliorate AD pathology.

Method

To test this, we used the TgF‐344AD rat model that develops AD in an age dependent manner. TZ treatment starts at 5 months of age (pre pathology) until 11 months of age (moderate pathology). At 9 and 11 months of age, we used the active place avoidance test to compare the hippocampal‐dependent spatial and working memory of the transgenic not treated (TGNT) and transgenic treated (TGTR) rats with terazosin. Wild type rats were also tested as a control.

Results

Our data indicate that TZ significantly improves spatial and working memory of TGTR when compared to TGNT rats. Additionally, immunohistochemical (IHC) analysis show beneficial effects of TZ in decreasing Ab plaques in cornu ammonis 1 (CA1) and subiculum (SB) subregions of hippocampus in transgenic rats. Further, ongoing analysis will reveal the effects of TZ on neuroinflammation in TGTR rats. Future studies will perform IHC on pTau and NeuN, RNAseq, western blots, and luciferase assay on the treated and untreated Tg‐AD groups to test the effects of TZ on other AD pathologies.

Conclusion

Overall, this study will decipher the potential of TZ to treat AD and present new molecular candidates that can be targeted to cure or delay the progression of AD.
Population‐based age‐specific estimates of dementia in Canada
Authors: Collin Lindsay J , Lally Cathy , Flanders W Dana , Maserejian Nancy N , Gillis Cai
Published: January 2025

Background

Dementia is a heterogeneous syndrome caused by diseases that impact cerebral functioning leading to progressive cognitive decline and loss of functional independence. Approximately 55 million people worldwide are living with dementia; however, population‐based estimates of dementia are challenging due to non‐standardized surveillance in most countries. We estimated the number of dementia cases among Canadian residents in 2022.

Method

To create age‐specific estimates of dementia in Canada, we compiled data from Statistics Canada. These data included the 2021 Canadian Census (to estimate the total population and type of residence—institutionalized vs. non‐institutionalized), the 2019/2020 Canadian Community Health Survey (to estimate the number of non‐institutionalized persons with dementia), and the 2013 Survey of Neurological Conditions in Institutions in Canada (to estimate the number of institutionalized persons with dementia). These data were used to compute estimates of the number of persons with dementia by age group (65‐69, 70‐74, 75‐79, 80‐84, 85‐89, 90+) in Canada in 2022. Using the overall Canadian population estimates for these age groups, we then calculated age‐specific estimates of dementia per 100,000 persons.

Result

In 2022, approximately 364,280 individuals 65+ years in Canada were living with dementia and the prevalence increased by age. Among those 65‐69 years the estimated prevalence of dementia was 1,343 per 100,000 persons and increased to 25,350 per 100,000 persons among those 90+ years. The prevalence of dementia in non‐institutionalized Canadians 65+ years was approximately 2.1%, and the prevalence among institutionalized Canadians was 52.5%. Of those with dementia, 41% were non‐institutionalized and 59% institutionalized. The proportion of non‐institutionalized dementia cases exceeded the institutionalized cases among those younger than 80 years (65% vs. 35%); however, for those 80+ years, there was a higher proportion of institutionalized cases compared with non‐institutionalized cases (71% vs. 29%).

Conclusion

Dementia is a substantial source of morbidity in Canada, with increasing prevalence in an aging population. Standardized surveillance is necessary to understand the needs of this growing patient population, which would lead to more reliable estimates and allow for proper allocation of resources to improve care.