bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding Complexity: Readability Analysis of Public Online Health Information on Common Neurological Diagnoses
Authors: Punukollu Manvi , Venkatesan Archana
Published: January 2025

Background

Alzheimer’s disease poses significant global health challenges, particularly as people increasingly turn to online platforms for health information in the digital era. Given the intricate nature of Alzheimer’s, it is imperative to evaluate the readability of online content. This study aims to assess the readability of information related to Alzheimer’s disease on reputable health websites.

Method

We carefully selected websites based on authority and prevalence through Google, the most popular search engine. Utilizing the neutral term “Alzheimer’s” ensured a broader sample of websites. We identified common domains within the top ten search results and meticulously sorted and saved them. Texts were then extracted and cleaned using Microsoft Office Excel. To evaluate readability, we employed various readability formulas using Python. The Flesch Reading Ease Score (FRES), Flesch–Kincaid grade level (FKGL), Simple Measure of Gobbledygook (SMOG), Gunning Fog (GFOG), Coleman–Liau score (CL), automated readability index (ARI), and Linsear Write (LW) were utilized.

Result

When comparing our readability results to the sixth‐grade level recommended by the American Medical Association and the National Institute of Health, we observed that the scores exceeded the recommended level. Findings from widely used internet resources revealed variations in readability scores across different websites. Notably, publicly accessible data related to Alzheimer’s disease tends to be presented at a higher reading level than recommended for general comprehension, carrying critical implications for patient education and health literacy within the Alzheimer’s context.

Conclusion

Assessing the readability of online health information for Alzheimer’s disease is crucial to ensure accessibility and comprehension for diverse audiences. This study provides valuable insights into the readability landscape of reputable health websites, uncovering a potential gap between the complexity of information and the general public’s reading ability in the context of Alzheimer’s disease. Recognizing and addressing this gap is essential for enhancing patient education and empowerment, ultimately contributing to improved health outcomes in the realm of Alzheimer’s.
Identifying feature relevance for transition from Questionable‐ to Low‐ AD using Interpretable‐AI
Authors: Beerapalli Sai Sanhitha
Published: January 2025

Background

In the face of increasing Mild Cognitive Impairment(MCI) and Dementia rates among aging populations, understanding the factors shaping the non‐normal cognitive decline is crucial. Leveraging the Clinical Dementia Rating (CDR) data, this study has a dual focus. (1) It utilizes CDR to aid early MCI diagnosis by investigating factors contributing to transition from Questionable‐ to Low‐ AD. (2) It undertakes a comparative analysis between Indian and Caucasian populations, acknowledging cultural influences on cognitive health.

Method

SHAP analysis (Lundberg et al, 2017), a game‐theory based explainable‐AI technique, performed on classifier accurately classifying Questionable‐ and Low‐AD subjects of Indian population (LASI‐DAD study) and Caucasian population(ADNI‐CDR study) to identify relevance of features for transition from Questionable‐ to Low‐AD. In extension, scatter Index analysis of SHAP values help identify the distribution of influence along with the the pivotal features that played significant role in the classification.

Result

Balanced datasets comprising 472 subjects of Caucasian population and 188 subjects of Indian population have been examined. SHAP analysis of logistic regression model with classification accuracy of 98%‐ADNI and 97%‐LASI yielded highest mean absolute value for Community domain (0.13) in ADNI data and Orientation domain (0.14) in LASI‐DAD data. Scatter Index of SHAP values resulted in scatter index deviation of 14.8% for Questionable‐AD and 26.8% for Low‐AD in Caucasian population; and 13.9% for Questionable‐AD and 13.6% for Low‐AD in Indian population. The analysis revealed that for ADNI data the distribution of feature importance is highly skewed to Community Affairs and for LASI data the feature importance is highly skewed to Orientation skills.

Conclusion

Performance of individuals in Orientation domain is the most important feature affecting the transition from Questionable‐AD to Low‐AD in the Indian population, while Community affairs is the most important in Caucasian population. Worsening of the performance in those particular domains is the biggest key factor in conversion to Low MCI. Although CDR is heavily dependent on Memory scores, while analyzing the transition from Questionable‐AD to Low‐AD in particular, it is not the most important factor.
Human restricted CHRFAM7A mediates neuronal and innate immune gain of function
Authors: Szigeti Kinga , Ihnatovych Ivanna , Dorn Ryu , Rosas Nicolas , Gomez Eduardo Cortes , Wilding Gregory , Jianmin Wang
Published: January 2025

Background

Understanding the fundamental differences between the human and pre‐human brain is a prerequisite for designing meaningful models and therapies for AD. Expressed CHRFAM7A, a human restricted gene with carrier frequency of 75% in the human population predicts profound translational significance.

Method

The physiological role of CHRFAM7A in human brain is explored using multiomics approach on 600 post mortem human brain tissue samples (ROSMAP). The emerging pathways are tested and validated in an isogenic hiPSC model of CHRFAM7A knock‐in neurons and monocytes. In vivo validation is performed in a double blind pharmacogenetic study on the effect of nicotinic acetyl‐choline esterase inhibitor therapy. The effect of CHRFAM7A carrier status was assessed in two paradigms: response to drug initiation and disease modifying therapy (DMT) effect over an 8 year observation period. Fitted general linear model independent variables included age, sex, and medication regimen at the time of the first MMSE, APOE4 carrier status (0, 1 or 2 alleles as categorical variables) and CHRFAM7A genotype.

Result

CHRFAM7A is identified as a modulator of intracellular calcium dynamics and an upstream regulator of Rac1. Rac1 activation re‐designs the actin cytoskeleton leading to dynamic actin driven remodeling of membrane protrusion and a switch from filopodia to lamellipodia. Phenotypic readouts in both the neuronal and monocytic lineages confirm actin cytoskeleton gain of function. The actin cytoskeleton reorganization shifts dendritic spine differentiation from filopodia towards spines with increased head area to stem diameter ratio resulting in increased synapse clustering (“high quality wellcro”) in neurons. In monocytes, the reorganized actin cytoskeleton leads to increased invasion, phagocytosis and cytokine release. These data suggest a shift from neurodegenerative to neuroinflammatory mechanism in 75% of AD patients. From the cholinergic treatment perspective incorporation into the a7 nAChR pentamer results in a hypomorphic receptor, which has diminished response to pharmacological modulation. Proof of principle pharmacogenetic study found a CHRFAM7A effect on treatment response both in the acute response and DMT paradigms.

Conclusion

Human restricted CHRFAM7A defines the biological background for AD pathology by shifting neurodegeneration to neuroinflammation in a 25‐75% split. Introducing a CHRFAM7A model into the target selection workflow may increase clinical trial success.
Immediate post‐diagnostic support for people with dementia and thier care partners: Scoping literature review
Authors: Pavkovic Sladana , Goldberg Lyn R. , Alty Jane E , Abela Melissa , Low Lee‐Fay
Published: January 2025

Background

Timely post‐diagnostic support is necessary to assist people living with dementia and their families to preserve their independence and to facilitate emotional and practical adaptation to dementia diagnosis and life after diagnosis. However, there is a noticeable scarcity of evidence concerning support following dementia diagnosis.

Our objective was to examine the following aspects: the nature and type of evidence pertaining to post‐diagnostic support within the initial two years of diagnosis; the conceptualization of post‐diagnostic support; and the existing gaps in the literature concerning this essential support.

Method

We conducted a comprehensive scoping literature review following the systematic process outlined by the Joanna Briggs Institute (JBI), employing the Population‐Who, Concept‐What, Context‐With What Qualifiers (PCC) protocol. All relevant keywords and index terms were systematically searched across PubMed, Scopus, CINAHL, and PsychInfo databases. The review encompassed evidence spanning from 2005 to 2023. The screening process is visually represented in the PRISMA diagram. Subsequently, two authors independently applied critical appraisal to the studies using the Mixed Method Appraisal Tool.

Result

For eligibility, a total of 506 articles were assessed, leading to the inclusion of 29 papers derived from 26 studies characterized by high methodological quality. Notably, the majority of these articles (n = 14, from 12 studies) were authored by researchers based in the UK. High methodological quality was reflected in various types of evidence, encompassing reviews (n = 2), mixed studies (n = 8), quantitative studies (n = 9), and qualitative studies (n = 7).

Specialist memory clinic support emerged as the most prevalent form of assistance during the initial two years following a dementia diagnosis. This support varied in its implementation, with some studies indicating support provided in (n = 12) or by (n = 5) memory clinics. Additionally, other studies presented post‐diagnostic support through diverse avenues, including day centres, on‐going support workers; home support programs, and community or non‐government organization initiatives.

Conclusion

A notable literature gap exists in immediate post‐diagnostic support for people with dementia and care partners. However, it remains unclear whether this gap is confined to the literature alone or extends to actual practice. Further research is imperative to delve into the support programs following dementia diagnosis, with a specific emphasis on settings beyond memory clinics.
Enhancing Accessibility: Readability Analysis of Alzheimer’s Disease Information on Reputable Health Websites
Authors: Punukollu Manvi , Venkatesan Archana
Published: January 2025

Background

Alzheimer’s disease poses significant global health challenges, particularly as people increasingly turn to online platforms for health information in the digital era. Given the intricate nature of Alzheimer’s, it is imperative to evaluate the readability of online content. This study aims to assess the readability of information related to Alzheimer’s disease on reputable health websites.

Method

We carefully selected websites based on authority and prevalence through Google, the most popular search engine. Utilizing the neutral term “Alzheimer’s” ensured a broader sample of websites. We identified common domains within the top ten search results and meticulously sorted and saved them. Texts were then extracted and cleaned using Microsoft Office Excel. To evaluate readability, we employed various readability formulas using Python. The Flesch Reading Ease Score (FRES), Flesch–Kincaid grade level (FKGL), Simple Measure of Gobbledygook (SMOG), Gunning Fog (GFOG), Coleman–Liau score (CL), automated readability index (ARI), and Linsear Write (LW) were utilized.

Result

When comparing our readability results to the sixth‐grade level recommended by the American Medical Association and the National Institute of Health, we observed that the scores exceeded the recommended level. Findings from widely used internet resources revealed variations in readability scores across different websites. Notably, publicly accessible data related to Alzheimer’s disease tends to be presented at a higher reading level than recommended for general comprehension, carrying critical implications for patient education and health literacy within the Alzheimer’s context.

Conclusion

Assessing the readability of online health information for Alzheimer’s disease is crucial to ensure accessibility and comprehension for diverse audiences. This study provides valuable insights into the readability landscape of reputable health websites, uncovering a potential gap between the complexity of information and the general public’s reading ability in the context of Alzheimer’s disease. Recognizing and addressing this gap is essential for enhancing patient education and empowerment, ultimately contributing to improved health outcomes in the realm of Alzheimer’s.
Brain effects of 5:2 intermittent fasting and the healthy living diet in a randomized controlled trial
Authors: Manolopoulos Apostolos , Mullins Roger J , Delgado‐Peraza Francheska , Mustapic Maja , Nogueras‐Ortiz Carlos , Yao Pamela J. , Cookson Mark R , Egan Josephine M. , Frangou Sophia , Mattson Mark P. , Kapogiannis Dimitrios
Published: January 2025

Background

Insulin Resistance (IR) is implicated in brain aging and Alzheimer’s disease (AD) pathogenesis. Dietary changes may promote brain health in older adults with metabolic abnormalities. An extensive animal literature suggests pro‐cognitive and beneficial systemic and brain effects of intermittent fasting (IF) that may mitigate AD risk. We conducted a randomized clinical trial comparing brain effects and the potential for AD biomarker modulation of IF and a continuous diet.

Method

Forty overweight, cognitively intact individuals > 55 years old with peripheral IR were randomized (1:1) to 5:2 IF (2 days 480 Kcal/day; 5 non‐restricted days) or Healthy Living (HL) diet by USDA recommendations for 8 weeks.

Result

Both IF and HL improved biomarkers of brain IR in neuron‐derived extracellular vesicles (NDEVs), decreased regional BrainAGE (brain‐age‐gap estimate on structural MRI) in the anterior cingulate and ventromedial prefrontal cortex, reduced glucose concentration on brain magnetic resonance spectroscopy (MRS) indicating optimized metabolism, and improved executive function and memory. Moreover, both diets decreased weight, BMI, and waist circumference suggesting high compliance, and HOMA2‐IR indicating IR alleviation. They also increased blood beta‐hydroxybutyrate and acetoacetate suggesting increased ketogenesis. Although effects of IF and HL were statistically comparable, greater numerical improvements were observed with IF for several measures of brain health, cognition, and peripheral metabolism. However, cerebrospinal fluid (CSF) and NDEVs showed no changes in AD biomarkers (Aβ42, total Tau, p181‐Tau, GFAP). In exploratory analysis, effects were moderated by polymorphisms in ApoE ε4 genotype, with cognitive benefits and decreased MRS glucose solely in ε4 non‐carriers; ε4 carriers showed no cognitive benefits, no decreases in MRS glucose, but increased CSF Aβ42/Aβ40 ratio, NfL and GFAP.

Conclusion

Beneficial effects of HL and, especially, IF on NDEV‐derived brain IR, BrainAGE, brain glucose concentration, executive function and memory indicate that healthy diets may improve brain health even over short periods of time, albeit with no evidence for AD cascade modulation. Genetic factors, such as ApoE ε4 polymorphisms, may influence the brain’s response to diets. Future clinical trials encompassing IF and other dietary interventions and stratified by ApoE ε4 carrier status may provide avenues for slowing the pace of brain aging.
Real‐world analysis of the clinical care pathway of patients living with Alzheimer’s disease in the United States according to stage of cognitive impairment at diagnosis
Authors: Fazio‐Eynullayeva Elnara , Cotton Sarah , Jones Eddie , Kirkman Sophie , Mystkowski Paul , Mattke Soeren , Lv Lei
Published: January 2025

Background

We analyzed the clinical care pathway of patients from symptom development to diagnosis at varying stages of Alzheimer’s disease (AD) to understand the path and barriers to diagnosis.

Methods

Data were from the US Adelphi Real World Dementia Disease Specific Programme™ (cross‐sectional survey of physicians and their patients with retrospective data collection) between December 2022 and September 2023. Physicians (primary care physicians [PCPs] and specialists) reported patient characteristics and disease severity, and patients reported their disease experience. Patients were aged ≥50 years with probable AD based on physician diagnosis and cognitive impairment severity assessed by Mini‐Mental State Examination (MMSE) scores: 26‒29, mild cognitive impairment (MCI) due to AD; 21‒25, mild AD dementia; 11‒20, moderate AD dementia; 0‒10, severe AD dementia.

Results

Overall, 191 physicians (83 PCPs, 108 specialists) reported data for 870 patients. Mean (SD) age was 74.7 (8.4) years and 48.3% of patients were female. At initial diagnosis, 22% of patients had MMSE scores consistent with MCI due to AD, 49% mild AD dementia, 26% moderate AD dementia and 2% severe AD dementia.

Irrespective of AD severity, short‐term memory loss prompted first physician evaluation for 83% of patients. Most patients (53.1%) delayed evaluation because they perceived memory issues to be a normal part of aging.

Median (IQR) time between symptom onset and first evaluation was 17.3 (4.4;43.4) weeks, and time from first evaluation to diagnosis was 3.0 (0.0;13.1) weeks. Around half of patients (47.0%) were referred to a secondary physician before diagnosis, with median (IQR) time from first evaluation to referral of 8.7 (2.3;19.9) weeks. For referred patients, median (IQR) time from first evaluation to diagnosis was 9.9 (3.1;26.2) weeks.

In 75.3% of cases, patients first visited a PCP (range: 71.4‐76.8%, across severity subgroups). Specialists made 57.9% of initial diagnoses versus 41.8% by PCPs; 61.9% versus 38.1%, respectively, for MCI due to AD and 57.1% versus 42.9%, respectively, for severe AD dementia.

Conclusion

While specialists and PCPs both diagnosed AD across all stages, specialists were more likely to diagnose patients in the MCI stage. Delays in AD diagnosis are common and new strategies to address these are warranted.
Hypothalamic substructural integrity is associated with age, sex and cognitive function across lifespan: A comparative analysis of two large population‐based cohort studies
Authors: Xu Peng , Estrada Santiago , Etteldorf Rika , Liu Dan , Shahid Mohammad , Frueh Deborah , Reuter Martin , Breteler Monique M.B. , Aziz N. Ahmad
Published: January 2025

Background

The hypothalamus is the body’s principal homeostatic center and plays a crucial role in the modulation of cognition. However, detailed assessments of age and sex effects on hypothalamic substructural integrity and its cognitive correlates across lifespan are still lacking. Therefore, we aimed to investigate the hypothalamic structural integrity in relation to age, sex and cognitive performance across lifespan in the general population.

Method

We used cross‐sectional data from the Rhineland Study (RS) (N = 5816, 55.2 ± 13.6 years, 58% women) and the UK Biobank Study (UKB) (N = 45076, 64.2 ± 7.7 years, 53% women), two large‐scale population‐based cohort studies. Volumes of hypothalamic structures were derived from 3T structural magnetic resonance images through application of a recently developed automatic parcellation procedure (FastSurfer‐HypVINN). The standardized cognitive domain scores were derived from extensive neuropsychological test batteries. We employed multivariable linear regressions to assess the age and sex effects on volumes of hypothalamic structures, and the relation between these volumes and cognitive function.

Result

Mean volumes of the total hypothalamus were 1188.4 mm3 (SD 113.6) in RS and 1101.9 mm3 (SD 119.9) in UKB. With increasing age, the volumes of total, anterior and posterior hypothalamus and mammillary bodies decreased (betas between ‐1.22 to ‐0.09 mm3/year in RS and between ‐3.84 to ‐0.49 mm3/year in UKB), and of medial hypothalamus and tuberal region increased (betas between 0.38 to 0.74 mm3/year in RS and between 0.21 to 0.68 mm3/year in UKB). Volumes of all hypothalamic structures were larger in men compared to women. Larger posterior hypothalamus volumes were associated with better global cognition (b ± standard error (SE): 0.033 ± 0.014 [RS] and 0.028 ± 0.006 [UKB], both p<0.001) and total memory (0.033 ± 0.018 [RS] and 0.015 ± 0.008 [UKB], both p,0.001), while larger anterior hypothalamus volumes were related to better executive function (0.028 ± 0.019 [RS] and 0.026 ± 0.011 [UKB], both p<0.004).

Conclusion

We found strong age and sex effects on hypothalamic structures, as well as robust associations between these structures and domain‐specific cognitive functions. Overall, these findings thus implicate specific hypothalamic substructures as both markers of age‐associated cognitive decline and potential targets for future interventions.
Tau Positivity for Flortaucipir using a Commercial Tau Quantification Software: Comparison to Visual Interpretation
Authors: Fahmi Rachid
Published: January 2025

Background

18F‐flortaucipir allows in‐vivo visualization of tau tangles in Alzheimer’s disease (AD) with a standardized definition of tau‐PET positivity. However, semi‐quantification is often used in research and in therapeutic trials and plays an important role in the AT(N) framework. This work aims to determine quantitative positivity thresholds and compare semi‐quantification to visual interpretation.

Method

N=189 flortaucipir scans from A05 (NCT02016560) study were included (15 young‐controls (YC), 48 elderly cognitively unimpaired (eCU), 85 MCIs, and 41 with AD) (Table 1), wherein the scans were visually interpreted as either T+/T‐. Using a PET‐only tau quantification software, volume‐weighted SUVRs were calculated on Braak I‐II, Braak III‐IV, Braak V‐VI, and temporal‐meta region (TMR) (Figure 3). Three methods to calculate T+ cut‐points were used: (T1) Youden‐index (MCI/AD vs. Aβ‐ eCU), (T2) mean+2SDs of Aβ‐ eCU, and (T3) mean+2SDs of YC SUVRs. Using calculated cut‐points, a subject is hierarchically assigned to a Braak stage if they are T+ at that stage and at all previous stages, otherwise, the subject is Braak‐staging discordant.

Result

Patients characteristics and visual A+/T+ proportions are summarized in Table 1. T1‐derived thresholds are: 1.26 (Braak I‐II), 1.18 (Braak III‐IV), 1.17 (Braak V‐VI), and 1.29 (TMR) (Table 2). TMR‐based T+ threshold using T2 was 1.30. Overall, the concordance of visual read with TMR‐based quantification was 92%, 93%, and 88.4%, and only 8/189 (4.2%), 6/189 (3.2%), and 0% subjects were Braak staging discordant, using thresholding methods T1, T2, and T3, respectively (Figure 2b). Braak staging was associated with cognitive decline (MMSE and ADAS‐Cog‐11), and with increase in A+/T+ proportions. All Braak V‐VI subjects had a T+ visual read. These subjects were also all Aβ+ MCI/ADs. However, 80% (8/10) of Braak III‐IV, 26.9% (7/26) of Braak I‐II, and 86% (44/51) of TMR+ subjects, using T1‐derived thresholds, had a T+ read, whereas 95.7% (44/46) of TMR+ subjects who were also Aβ+ had a T+ read.

Conclusion

Using the temporal‐meta region, visual read and SUVR were highly concordant. Visual T+ aligns more with amyloid positivity. Hierarchical Braak staging was associated with cognitive performance and amyloid load and its concordance with visual interpretation was moderate‐to‐high for the limbic and neocortical stages.
Lower Risk of Alzheimer’s Disease and Related Dementias associated with Angiotensin Receptor II Blockers (ARBs) treatment for individuals with Hypertension in High‐volume Claims Data
Authors: Lundin Sori Kim , Hu Xinyue , Feng Jingna , Lundin Karl Kristian , Li Lu , Chen Yong , Schulz Paul E , Tao Cui
Published: January 2025

Background

Findings regarding the protective effect of Angiotensin II receptor blockers (ARBs) against Alzheimer’s disease and related dementias (ADRD) and cognitive decline have been inconclusive.

Method

A total of 6,390,826 hypertensive individuals were included in this study from Optum’s de‐identified Clinformatics® Data Mart. We identified antihypertensive medication (AHM) drug classes and subclassified ARBs by blood‐brain barrier (BBB) permeability. We compared baseline characteristics and used the Kaplan‐Meier (KM) survival curve and adjusted Cox proportional hazards (PH) model for survival analyses.

Result

AHM non‐users (N = 1,184,809) had a lower incidence of all comorbidities and consumption of metformin and statins compared to ARBs users (N = 1,839,176) and non‐ARBs AHM users (N = 3,366,841) (all P<0.0001). The KM curve showed that ARB users had lower cumulative hazard than other AHM users or AHM non‐users (P<0.0001). In Cox PH analysis, ARB users showed a 20% lower adjusted hazard of developing ADRD compared to angiotensin‐converting enzyme inhibitor (ACEI) users and a 29% and 18% reduced risk when compared to non‐ARB/ACEI AHM users and AHM non‐users (all P<0.0001). Consumption of BBB‐crossing ARBs was linked to a lower risk of ADRD development than non‐BBB‐crossing ARBs, undetermined ARBs, and non‐consumption of AHMs by 11%, 25%, and 31% (all P<0.0001).

Conclusion

This study suggests that ARBs are superior to ACEIs, non‐ARB/ACEI AHMs, or non‐use of AHMs in reducing the risk of ADRD among hypertensive patients. Also, BBB‐permeability in ARBs was associated with lower ADRD risk. There is no cure for AD, ADRD, or vascular dementia; hence, these findings are significant in preventing those disorders in an inexpensive, convenient, and safe way.
Advance Care Planning Among Diverse U.S. Older Adults with Varied Cognition Levels
Authors: Rahemi Zahra , Adams Swann Arp
Published: January 2025

Background

Older adults from minority groups often experience elevated rates of chronic diseases and cognitive impairment, coupled with lower rates of engagement in advance care planning (ACP) and comfort care as they approach end of life. The complexities of ACP and end‐of‐life care become particularly pronounced in older adults with cognitive impairment. As cognitive and decisional capacity changes, healthcare decisions are commonly delegated to family members or proxies. This can present challenges, especially when life expectations are uncertain and discussions regarding ACP have not taken place. This study explores the disparities in ACP among diverse U.S. older adults with varying levels of cognitive function.

Method

Secondary data analyses were performed utilizing the 2014 Health and Retirement Study. The outcome variables assessed were the possession of a living will, durable power of attorney for healthcare (DPOAH), and both a living will and DPOAH. Logistic regression models were applied to each outcome variable (living will, DPOAH, and both) with stratification based on cognition (dementia/impaired cognition versus normal cognition). Prediction variables encompassed race, ethnicity, rurality, marital status, gender, education, age, and social support.

Result

Among the 17,698 respondents, 77.8% exhibited normal cognition, while 22.2% received a diagnosis of dementia or impaired cognition. Black and Hispanic participants, as well as younger individuals with lower levels of education, demonstrated a reduced likelihood of having a living will or both DPOAH and a living will. In the normal cognition group, race and ethnicity emerged as significant predictors of DPOAH, but this association was not observed in the dementia group. Additionally, rurality significantly predicted the presence of a living will and both DPOAH/living will for the normal cognition group, while such an association was not evident in the dementia/impaired cognition group.

Conclusion

Our study revealed that individuals facing cognitive impairments exhibited lower rates of engagement in ACP. Notably, among the variables examined, race, ethnicity, rural residence, education, and age emerged as significant predictors of ACP in a national sample of older adults in the U.S. These findings underscore the importance of incorporating these sociodemographic factors into the design of interventional studies aimed at enhancing ACP and mitigating disparities.
Analyzing Response Rates and Respondent Demographics in Online Surveys Assessing Public Perception of Alzheimer’s Disease‐Modifying Therapies
Authors: Nakashima Saki , Sato Kenichiro , Niimi Yoshiki , Toda Tatsushi , Iwatsubo Takeshi
Published: January 2025

Background

With the recent approval of lecanemab, a disease‐modifying therapy (DMT) for Alzheimer’s Disease (AD), there is an urgent need to address healthcare system challenges to ensure the safe, effective, and sustainable delivery of approved DMT drugs.

Understanding public perceptions of these challenges through online surveys might be helpful. Achieving sufficient responses that reflect the characteristics of the respondents is crucial for a successful online survey, however, details about the respondent characteristics for this kind of survey are largely uncertain.

Method

We analyzed data from an anonymous online survey conducted using Google Forms from November 28 to December 16, 2023 to participants of a Japanese trial‐ready cohort (J‐TRC) web study, a web‐based online registry aiming to enroll individuals with preclinical AD to facilitate AD prevention trials.

Result

Among approximately 10,400 J‐TRC web study participants to whom we sent invitation e‐mails, we received 1,761 responses (16.9% response rate) within two weeks of the response acceptance period. The demographic split of survey respondents was 47% male and 52% female, primarily between the ages of 50‐70. Male respondents were more predominant in older age groups (Chi‐squared p<0.001). Regarding the days of the week when invitation e‐mails were sent (Tuesday to Saturday), Tuesday had the highest response rate, followed by Saturday, Wednesday, Thursday, and Friday. Female respondents were more predominant on Wednesday, Friday, and Saturday. Respondents from Tuesday to Friday were more likely to be retirees, whereas those on Saturday were not. The effect of retirement on increasing response rates was more pronounced in males than in females.

Conclusion

Our analysis evaluated the response rate and respondent characteristics for an online survey concerning public perceptions of DMTs for AD. The current results could be useful for future efforts to improve response rates of online surveys targeting health‐conscious individuals aged 50‐80 with an interest in dementia treatment, by optimizing the timing and methods of sending survey invitations.
Frontal Memory‐related Brainwaves Differentially Correlate with AD and Astrocyte Plasma Biomarkers
Authors: Jiang Yang , Wu Xian , Katsumata Yuriko , Clark Maria F , Foley Kate E. , Wang Baoxi , Sudduth Tiffany L. , Wilcock Donna M. , Jicha Gregory A , Norris Christopher M.
Published: January 2025

Background

We currently lack in the dementia field accurate, noninvasive, quick, and affordable screening tools for brain dysfunctions associated with early subtle risk of mild cognitive impairment (MCI). Our Kentucky aging cohort demonstrates that asymptomatic older individuals with MCI‐like frontal memory‐related brainwave patterns convert to MCI within a short 5‐year period, as opposed to individuals with NC‐like patterns (1) that remain normal 10 years later (2). Astrocyte reactivity influences amyloid‐β effects on tau pathology in preclinical Alzheimer’s disease (3). Leveraging blood‐based AD and astrocyte biomarkers and the cognitive electroencephalogram (EEG) signatures (4), we test the hypothesis that predictive frontal memory‐related EEG changes correlate with preclinical and early AD plasma biomarkers.

Method

34 (19 women) older volunteers with or without MCI, average age 79 (SD 8.53) years old, from a longitudinal cohort followed by University of Kentucky ADRC participated. Each participant’s EEG was recorded (64‐ or 14‐channels) during a working memory (modified delayed match‐to‐sample) task. Principal component analysis (PCA) was performed on 64‐channel EEG data to create PC scores (PC1 & PC2). For multiple linear regression of EEG PC scores on multiple neurodegenerative plasma biomarkers including Aβ42/40, pTau181, total Tau, and GFAP (Astrocyte reactivity), we adjusted age, sex, education, and gap years between collection dates.

Result

The 61% of variance in frontal signals can be explained by PC1 in normal cognition (NC) and MCI individuals, and PC2 counts for 35% of variance (Figure 1). The decreased brainwaves (MCI‐like) seen in left frontal sites significantly correlate with increased pTau181, GFAP, and PC2 (Figure 2). Curiously, right frontal EEG relations with pTau181, GFAP showed the opposite trend. Bilateral frontal signals showed negative correlations with Aβ42/40 and positive correlations with total Tau.

Conclusion

Our results indicate that GFAP & pTau181 trend in similar asymmetry ways with frontal cognitive brainwaves, but Aβ42/40 & total Tau correlate to a different component of frontal EEG. That is, distinct cognitive brainwaves correlate with astrocyte reactivity differentially that influence pathologies of beta‐amyloid accumulations and Tau development. Cognitive pathophysiological signatures and AD–Astrocyte plasma biomarkers have great potential for predicting subtle cognitive decline and specific dementia risk in healthy normal individuals.
EEG‐guided anesthetic titration and perioperative cognitive disorders
Authors: Evered Lisbeth Anne
Published: January 2025

Background

Postoperative delirium (POD) is a serious complication of surgery associated with prolonged hospitalisation, long‐term cognitive decline, dementia and mortality. There is increasing evidence that electroencephalography (EEG) monitoring may reduce the incidence of POD, however, the best method for achieving this is unclear.

Method

This presentation will present the results of a multicentre randomised clinical trial of 515 at‐risk patients undergoing major surgery from 8 centres in 3 countries who were assessed for POD for 5 days postoperatively. They also underwent cognitive screening at baseline, discharge, 30 days and one year postoperatively. Patients were assigned to light or deep anaesthesia. Additionally, this presentation will consider a meta‐analysis of available studies investigating EEG monitoring to prevent delirium and outline the importance of EEG spectrogram interpretation as part of EEG monitoring and consequent anesthetic titration when using this technique to reduce or prevent POD.

Result

The incidence of POD was lower (19%) in the light anesthesia group compared with the deep anesthesia group (28%) (OR 0.58 (95% CI 0.38 to 0.88), P=0.010). Meta‐analysis results were fragile and depended on inclusion criteria of studies. Interpretation of EEG spectrograms is a developing field, but adds significant, critical information.

Conclusion

EEG monitoring is a possible method for preventing POD and long‐term complications. EEG spectrogram interpretation will likely add critical information to enhance this technique.
Real‐World Data on the diagnosis of Alzheimer’s Disease in routine clinical practice: Insights from the Australian Dementia Network “ADNeT” Registry
Authors: Ward Stephanie Alison , Lin Xiaoping , Wallis Kasey , Brodaty Henry , Rowe Christopher C. , Masters Colin L. , Naismith Sharon L , Ahern Susannah
Published: January 2025

Real‐world data on the uptake, effectiveness and safety of new diagnostics and disease‐modifying (DMT) treatments for Alzheimer’s Disease (AD) are imperative. This can be achieved through patient registries. A major challenge is how to embed registry data capture into routine clinical practice. To optimize coverage and maintain data contribution over time, registry participation needs to create maximal benefits, yet impose minimal burdens, on clinical sites.

In the experience of the Australian Dementia Network (ADNeT) Registry, it has been the unique insights that clinicians obtain into their own diagnostic practices that has incentivised ongoing participation. The ADNeT Registry collects data primarily to measure the quality of diagnosis and clinical care provided to people with either mild cognitive impairment or dementia and was pragmatically designed to be utilized in multiple diagnostic settings and by different clinical craft groups. Clinicians enter a brief minimum dataset, based upon routine clinical data, at the time of diagnosis. These data are augmented by the ADNeT Registry’s collection of patients and/or carer‐reported experience and outcome measures and will be further augmented by planned linkage with administrative datasets.

By January 2024, the ADNeT Registry had collected data on over 4000 participants, from 66 sites, had issued 4 benchmarked site reports, and published 2 annual reports. Of this cohort, 75% of people with dementia had an AD subtype. At the national level, considerable variation exists in diagnostic time intervals, and in the use of functional neuroimaging and biomarkers. At the individual site level, clinicians report regularly comparing their individual data against Registry benchmarked data to review, and if some cases, improve, their diagnostic approaches.

The Registry’s explicit focus on supporting clinicians is further enhanced by broader achievements of ADNeT, including the publication of memory clinic guidelines, streamlined processes for accessing clinical trials, and appropriate use recommendations for DMTs. Collectively, ADNeT and the ADNeT Registry provides a strong foundation for additional data capture on DMT prescription, safety, and outcome measures, with a design that helps ensure that collected data are truly reflective of the “real‐world”.
Unravelling the challenges of dementia home care in India
Authors: Dasgupta Jayashree
Published: January 2025

Background

India has a mixed public‐private healthcare system however most care is out‐of‐pocket. Despite projections that the older population is expected to rise from current 138 million to 194 million by 2031, services catering to the needs of people living with dementia remain limited. Ailing family members and older adults have traditionally been cared for in an intergenerational joint family system where members reside together. However, social transitions, including more women entering the workforce and migration, both within India and international migration, for better job opportunities, have led to changes in this traditional family system. This presents significant challenges for families as they end up providing majority of dementia care with limited professional support, limited knowledge and virtually no access to training, counseling and other support services.

Methods

Using a case study approach we describe the complexity of issues faced by Indian families. Cases were retrospectively sampled from families that availed services from an eldercare organization providing a range of services in Gurugram India, between Jan 2018 to March 2023. Using this approach, we specifically draw attention to 1) challenges faced by transnational Indian families when parents struggle to live independently 2) challenges faced by an only child due to limited dementia specific services 3) Dynamics within families as they navigate various aspects of decision making, finances and family relocation for dementia care.

Results

This presentation will highlight important themes that emerge and focus on areas which need to be addressed whilst developing homecare services for dementia in India. In particular, we highlight the need for professionally delivered family support, eldercare services tailored to dementia, training for a dementia ready work force in India, and the role that technology plays in supporting dementia care.

Conclusions

This qualitative and experiential account provides impetus for further work to develop culturally appropriate strategies to support dementia care in India.
The long‐term impact of rugby, soccer and boxing participation on brain health in older adults from the general population: insights from the 1946 British birth cohort
Authors: Parker Thomas D , James Sarah‐Naomi , Keuss Sarah E , Keshavan Ashvini , Coath William , Cash David M , Lu Kirsty , Nicholas Jennifer M , Sudre Carole H , Crutch Sebastian J , Fox Nick C , Richards Marcus , Schott Jonathan M
Published: January 2025

Background

In elite athletes, participation in sports associated with repetitive head injury exposure has been linked to an increased risk of neurodegeneration later in life. However, there has been limited study in more general populations. We aimed to investigate whether participation in such sports impacted outcomes relevant to brain health in a cohort of British‐born older adults.

Methods

441 participants from Insight 46 (a sub‐study of the 1946 British Birth Cohort) were asked whether they participated in rugby, soccer, or boxing, consistently for at least a year (yes/no) at various epochs of life (<20, 20‐49 and 50+ years). Individuals underwent baseline florbetapir‐PET, serial brain MRI and cognitive assessments (mean age at baseline assessment 70.6 years, mean interval between visits = 2.4 years). A range of life course data were included in analyses, including attitudes to sports, education, engagement in physical activity and self‐reported symptomatic head injury.

Result

As only one female identified as participating in rugby, soccer, or boxing, only males were included in analyses: 101/232 males (43.5%) stated they participated in at least one of these sports, 46 of whom participated for more than one epoch. Univariate analyses revealed participation was associated with a range of demographic factors including: a preference “to play rough sports” aged 13 (p<0.001); a higher level of education (p = 0.007); engagement in physical activity aged 36 (p<0.001); and 43 (p = 0.017); and greater risk of self‐reported symptomatic head injury (35.3% vs 14.7%, p<0.001).

There were no significant associations between participation in these sports and baseline cognitive function or decline, beta‐amyloid deposition, white matter hypertintensity volume, or baseline/longitudinal change in total brain or hippocampal volume (table 1).

Longer duration of participation (≥ two epochs vs one) was associated with lower hippocampal volume at baseline (p = 0.006) but did not predict subsequent atrophy or any other outcome examined (table 2).

Conclusion

Previous exposure to sports associated with repetitive head injuries is common amongst British‐born older adults and associated with a range of demographic factors relevant to brain health. Longer duration of exposure predicted lower hippocampal volume age 70 years, but there was no evidence of significantly accelerated atrophy or cognitive decline beyond this.
Diversity, Equity and Inclusivity‐ Low and Middle Income countries and the Lancet commission
Authors: Livingston Gill , Huntley Jonathan D , Liu Kathy Y , Gonzalez Sergi Costafreda , Selbaek Geir , Alladi Suvarna , Ames David , Banerjee Sube , Burns Alistair , Brayne Carol , Fox Nick C , Ferri Cleusa P , Gitlin Laura N. , Howard Robert J , Kales Helen C , Kivimäki Mika , Larson Eric B , Nakasujja Noeline , Rockwood Kenneth , Samus Quincy M , Shirai Kokoro , Singh‐Manoux Archana , Schneider Lon S. S. , Walsh Sebastian , Yao Yao , Sommerlad Andrew , Mukadam Naaheed
Published: January 2025

Background

Data from high‐income countries (HICs) suggest a decline in age‐specific incidence rates of dementia. However, this has happened primarily in HICs, with low‐ and middle‐ income countries (LMICs) facing two main challenges: a higher burden of risk factors and, in general, a faster ageing population. Most people with dementia live in LMICs, and this is set to increase, thus requiring urgent and robust action to prevent, treat and support people with dementia and their families.

Methods

We, in the Lancet Commission, reviewed the most recent literature, and conducted a new metanalysis on worldwide dementia risk. We have calculated worldwide figures, although there may be variation in different ethnic and socioeconomic groups.

Results

Dementia studies are overwhelmingly from HICs, and there is a tendency to recruit people of European origin with higher education and socioeconomic status, with few people from ethnic minority groups. The same applies in respect of worldwide clinical trials, including multicomponent interventions to reduce risk, biomarker research and pharmacological/non‐pharmacological interventions.

Although most interventions are developed in HICs, culturally adapted interventions seem to be as effective in LMICs as in their original context, as long as the interventions’ core components are not compromised in the adaptation process.

Conclusion

Policy interventions can improve dementia prevention, particularly in LMICs and in minority and lower level socio‐economic groups ‐ precisely the people who have the greatest burden of modifiable risk and are more likely to develop dementia.

Dementia prevention efforts should be tailored to the needs of the different countries and different groups within countries. Trials and research databases should aim for sociodemographic diversity to reflect real life populations.

Although evidence‐based interventions developed in HICs can be effective in LMICs, there is often a lack of healthcare infrastructure and resources to deliver them. Moreover, cultural differences can make them inappropriate or less effective. Interventions should be developed in partnership with local communities to ensure their appropriateness in respect of the culture, beliefs and practises which vary within and between countries.
Interventions for cognitive symptoms of dementia ‐ and the Lancet commission view on anti‐amyloid antibodies
Authors: Selbaek Geir
Published: January 2025

Background

While symptomatic treatment for Alzheimer’s disease has been available for three decades disease modifying treatment does not exist. New drug treatments, known as immunotherapies, which remove amyloid from the brain offer hope, but the clinical significance remains uncertain.

Method

Systematic reviews of the literature, expert consensus, and information from clinical environments.

Result

Cholinesterase inhibitors (ChEI) and memantine have repeatedly demonstrated a modest symptomatic effect on cognition and function in clinical trials and long‐term observational studies indicate that these drugs may lower mortality. They are readily available, relatively affordable, have few side‐effects and should be offered to patients with Alzheimer’s disease or Lewy Body dementias.

Treatment with the monoclonal antibodies lecanemab and donanemab consistently shows an effect on clinical measures, such as cognition, function, and quality of life. However, the effect size is small, and the results may not generalize to groups that are poorly represented in the clinical trials. Risk of serious adverse events, such as brain haemorrhages, may restrict the population eligible for treatment. Lecanemab has been granted marketing approval in USA, Japan and China and awaits decision in European countries, expected first half of 2024. Before implementation several issues need to be addressed. More people will need a more precise and biomarker‐based diagnosis at an earlier disease stage. The total treatment cost is huge. In addition to medication cost more resources will be needed for diagnostic testing, treatment administration and surveillance/monitoring of side effects. At present, very few countries can meet these requirements.

Conclusion

The advent of monoclonal antibodies represents a major scientific breakthrough in the quest to combat Alzheimer’s disease and might offer hope to people with the disease and their closest caregivers. Unfortunately, so far, the limited clinical gain may not offset treatment cost and risk of adverse events. Long‐term efficacy data and results from trials with treatment initiated at an earlier disease stage are needed to determine the meaningfulness of these new treatments. In parallel, other treatment options targeting tau protein, inflammatory pathways or metabolic dysfunction should be investigated further to offer people with Alzheimer’s disease and related dementias a personalized treatment regimen.