Ahead of print articles
JPAD Volume 12, N°01 - 2025
EXPERT OPINION ON CENTILOID THRESHOLDS SUITABLE FOR INITIATING ANTI-AMYLOID THERAPY. SUMMARY OF DISCUSSION AT THE 2024 SPRING ALZHEIMER’S ASSOCIATION RESEARCH ROUNDTABLE
Gill Farrar, Christopher J. Weber, Gil D. Rabinovici
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryA 24–30 Centiloid (CL) threshold was collectively considered by a group of global dementia experts as a practical and implementable cut-off for anti-amyloid therapy intervention, in Alzheimer’s disease patients who have been diagnosed at the mild cognitive impairment or mild dementia stage of their disease. Though additional validation is needed, knowledge of this threshold would be valuable to those involved in diagnosing and treating patients in the new AD care pathways, as well as entry into clinical trials. Therapy monitoring to determine future treatment response and assess amyloid clearance can be accomplished with amyloid PET with some technical details still to be elucidated.
CITATION:
Gill Farrar ; Christopher J. Weber ; Gil D. Rabinovici (2025): Expert opinion on Centiloid thresholds suitable for initiating anti-amyloid therapy. Summary of discussion at the 2024 spring Alzheimer’s Association Research Roundtable. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100008
POINT OF VIEW: CHALLENGES IN IMPLEMENTATION OF NEW IMMUNOTHERAPIES FOR ALZHEIMER\'S DISEASE
Sandar Aye , Gunilla Johansson , Christoph Hock , Lars Lannfelt , John R Sims , Kaj Blennow, Kristian S Frederiksen, Caroline Graff, José Luis Molinuevo, Philip Scheltens, Sebastian Palmqvist, Michael Schöll, Anders Wimo, Miia Kivipelto, Ron Handels, Lutz Frölich, Norbert Zilka, Martin Tolar, Peter Johannsen, Linus Jönsson, Bengt Winblad
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryThe advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists. Additionally, there are logistical concerns related to infrastructure, as well as cost-effectiveness and reimbursement issues.
This article brings together insights from a diverse group of international researchers and dementia experts and outlines the potential challenges and opportunities, urging all stakeholders to prepare for the introduction of DMTs. We emphasize the need to develop appropriate use criteria, including patient characteristics, specifically for the European healthcare system, to ensure that treatments are administered to the most suitable patients. It is crucial to improve the skills and knowledge of physicians to accurately interpret biomarker results, share decision-making with patients, recognize treatment-related side effects, and monitor long-term treatment. We advocate for investment in patient registries and unbiased follow-up studies to better understand treatment effectiveness, evaluate treatment-related side effects, and optimize long-term treatment. Utilizing amyloid-targeting therapies as a starting point for combination therapies should also be a priority.
CITATION:
Sandar Aye ; Gunilla Johansson ; Christoph Hock ; Lars Lannfelt ; John R Sims ; Kaj Blennow ; Kristian S Frederiksen ; Caroline Graff ; José Luis Molinuevo ; Philip Scheltens ; Sebastian Palmqvist ; Michael Schöll ; Anders Wimo ; Miia Kivipelto ; Ron Handels ; Lutz Frölich ; Norbert Zilka ; Martin Tolar ; Peter Johannsen ; Linus Jönsson ; Bengt Winblad (2025): Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD).https://doi.org/10.1016/j.tjpad.2024.100022
KEY CONSIDERATIONS FOR COMBINATION THERAPY IN ALZHEIMER\'S CLINICAL TRIALS: PERSPECTIVES FROM AN EXPERT ADVISORY BOARD CONVENED BY THE ALZHEIMER\'S DRUG DISCOVERY FOUNDATION
Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E. Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryThere is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress in combination therapy could be accelerated by leveraging preclinical research and Phase 1 and 2A trials to identify the most promising combinations for further development, exploring repurposed agents with available preclinical and clinical data, building collaborations across sectors to support operational challenges, and planning for the likely impact of anti-amyloid beta-protein monoclonal antibody therapies on future clinical trial designs.
CITATION:
Jeffrey Cummings ; Michael Gold ; Mark Mintun ; Michael Irizarry ; Andrew von Eschenbach ; Suzanne Hendrix ; Donald Berry ; Cristina Sampaio ; Kaycee Sink ; Jaren Landen ; Miia Kivipelto ; Michael Grundman ; Steven E. Arnold ; Allan Green ; Katherine Partrick ; Laura Nisenbaum ; Aaron Burstein ; Howard Fillit (2025): Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100001
INTERCEPT-AD, A PHASE 1 STUDY OF INTRAVENOUS SABIRNETUG IN PARTICIPANTS WITH MILD COGNITIVE IMPAIRMENT OR MILD DEMENTIA DUE TO ALZHEIMER\'S DISEASE
Eric Siemers, Todd Feaster, Gopalan Sethuraman, Karen Sundell, Vladimir Skljarevski, Erika N. Cline, Hao Zhang, Jasna Jerecic, Lawrence S. Honig, Stephen Salloway, Reisa Sperling, Mirjam N. Trame, Michael G. Dodds, Kimball Johnson
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.
OBJECTIVES:
To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).
DESIGN:
Randomized, double-blind, placebo-controlled, ascending dose first-in-human phase 1 study.
SETTING:
Fifteen study centers in the United States.
PARTICIPANTS:
Sixty-five participants with early symptomatic AD.
INTERVENTION:
Participants received one infusion of sabirnetug 2 mg/kg, 10 mg/kg, 25 mg/kg, 60 mg/kg, or placebo (Part A) or three infusions of sabirnetug 10 mg/kg, 25 mg/kg, 60 mg/kg, or placebo (Part B).
MEASUREMENTS:
Safety, tolerability, serum pharmacokinetics, and central target engagement of single and multiple doses of sabirnetug, cerebrospinal fluid (CSF) concentrations of sabirnetug, and amyloid plaque load, as determined by positron emission tomography.
RESULTS:
Sabirnetug was generally well tolerated. A larger percentage of participants receiving sabirnetug (56.3%) versus placebo (42.9%) had at least one treatment emergent adverse event, with approximately 29% in each group considered related to study drug. Most events were mild-to-moderate in severity. Of 48 participants given sabirnetug, five developed amyloid related imaging abnormalities – edema/effusion, including one instance that was mildly symptomatic in a participant who had received one dose sabirnetug 60 mg/kg. Notably, none of the six apolipoprotein E Ɛ4 homozygotes who received sabirnetug developed amyloid related imaging abnormalities – edema/effusion or – hemorrhage/hemosiderin deposition. Infusion reactions, such as rash, pain, or erythema, were not frequent (6.3% for sabirnetug versus 0.0% for placebo). Sabirnetug exposure was dose proportional in both serum and CSF. Target engagement, defined as drug bound to AβOs in CSF, was shown to be dose and exposure dependent. Over three months, approximately 25% and 20% reduction in amyloid plaques, respectively, were observed in participants receiving three infusions of sabirnetug 60 mg/kg every four weeks and 25 mg/kg every two weeks.
CONCLUSIONS:
The Phase 1 INTERCEPT-AD study provided safety, tolerability, dosing, and target engagement data that supported the design of the ongoing ALTITUDE-AD study (NCT06335173).
CITATION:
Eric Siemers ; Todd Feaster ; Gopalan Sethuraman ; Karen Sundell ; Vladimir Skljarevski ; Erika N. Cline ; Hao Zhang ; Jasna Jerecic ; Lawrence S. Honig ; Stephen Salloway ; Reisa Sperling ; Mirjam N. Trame ; Michael G. Dodds ; Kimball Johnson (2025): INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100005
BLARCAMESINE FOR THE TREATMENT OF EARLY ALZHEIMER\'S DISEASE: RESULTS FROM THE ANAVEX2-73-AD-004 PHASE IIB/III TRIAL
Stephen Macfarlane, Timo Grimmer, Ken Teo, Terence J O\'Brien, Michael Woodward, Jennifer Grunfeld, Alastair Mander, Amy Brodtmann, Bruce J. Brew, Philip Morris, Cathy Short, Susan Kurrle, Rosalyn Lai, Sneha Bharadwaj, Peter Drysdale, Jonathan Sturm, Simon J.G. Lewis, David Barton, Chris Kalafatis, Saif Sharif, Marwan N Sabbagh
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).
OBJECTIVES:
The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.
DESIGN:
ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.
SETTING:
Multicenter - 52 medical research centers/hospitals in 5 countries.
INTERVENTION:
508 participants with early AD (Stage 3) were randomized to receive either blarcamesine (n = 338) in medium dose group 30 mg or in high dose group 50 mg or placebo (n = 170) oral capsules once daily for 48 weeks. Participants in these groups were offered to enroll into the open-label-extension study ATTENTION-AD, which completed June 2024, ClinicalTrials.gov Identifier NCT04314934.
MEASUREMENTS:
The co-primary cognitive and functional outcomes were assessed as change in ADAS-Cog13 and ADCS-ADL from baseline to 48 weeks. The outcomes include the secondary outcome CDR-SB and biomarkers from the A/T/N spectrum, plasma Aβ42/40-ratio and global brain volume changes measured by MRI. All clinical endpoints were analyzed using mixed model for repeated measures (MMRM), plasma biomarker measurements were analyzed by Welch's t-test, and volumetric MRI scans were analyzed by general linear model.
RESULTS:
Among 462 randomized participants in the intent-to-treat population (mean age, 73.7 years; 225 [48.7%] women), 338 (73.2%) completed the trial. The co-primary outcome was met under the multiplicity control rule, since the differences in the least-squares mean (LSM) change from baseline to 48 weeks between the prespecified blarcamesine and placebo groups for ADAS-Cog13 was significant at a level of P < 0.025 and for CDR-SB was significant at a level of P < 0.025, while ADCS-ADL did not reach significance at Week 48 (ADAS-Cog13 difference of -2.027 [95% CI -3.522 to -0.533]; P = 0.008; CDR-SB difference of -0.483 [95% CI -0.853 to -0.114]; P = 0.010; ADCS-ADL difference of 0.775 [95%CI -0.874 to 2.423]; P = 0.357). Plasma Aβ42/40-ratio increased significantly with blarcamesine group vs. placebo, (P = 0.048) and whole brain volume loss was significantly decreased (P = 0.002). Participants in the full safety population with ≥1 serious treatment-emergent adverse events (TEAEs) occurred in 56 participants (16.7%) in the blarcamesine and 17 (10.1%) in the placebo group. Common TEAEs included dizziness, which was transient and mostly mild to moderate in severity. One death in the blarcamesine group and 1 in the placebo group were both not considered treatment related.
CONCLUSIONS:
Blarcamesine, demonstrating a safety profile with no associated neuroimaging adverse events, significantly slowed clinical progression by 36.3% at 48 weeks with blarcamesine group as well as the individual 30 mg (by 34.6%) and 50 mg (by 38.5%) blarcamesine groups vs. placebo on the prespecified primary cognitive endpoint ADAS-Cog13. The prespecified secondary endpoint CDR-SB, which is used as the sole primary endpoint in recent successful AD drug submissions, is significantly improved at Week 48 with blarcamesine relative to placebo. The findings are supported by biomarkers from the A/T/N spectrum, including plasma Aβ42/40-ratio and reduction of whole brain atrophy. Additionally, the prespecified SIGMAR1 gene variant subgroup analysis confirmed beneficial clinical effect of blarcamesine group through upstream SIGMAR1 activation - subjects with the common SIGMAR1 wild-type gene (excluding carriers of the mutated SIGMAR1 rs1800866 variant) experienced an even greater significant clinical benefit with slowed clinical progression by 49.8% at 48 weeks on the prespecified primary cognitive endpoint ADAS-Cog13. Oral once daily blarcamesine could represent a novel treatment in early AD and be complementary or alternative to anti-beta amyloid drugs.
CITATION:
Stephen Macfarlane ; Timo Grimmer ; Ken Teo ; Terence J O'Brien ; Michael Woodward ; Jennifer Grunfeld ; Alastair Mander ; Amy Brodtmann ; Bruce J. Brew ; Philip Morris ; Cathy Short ; Susan Kurrle ; Rosalyn Lai ; Sneha Bharadwa ; Peter Drysdale ; Jonathan Sturm ; Simon J.G. Lewis ; David Barton ; Chris Kalafatis ; Saif Sharif ; Marwan N Sabbagh (2025): Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100016
ARTIFICIAL INTELLIGENCE-ENABLED SAFETY MONITORING IN ALZHEIMER\'S DISEASE CLINICAL TRIALS
Gustavo A. Jimenez-Maggiora, Michael C. Donohue, Michael S. Rafii, Rema Raman, Paul S. Aisen
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
Investigators conducting clinical trials have an ethical, scientific, and regulatory obligation to protect the safety of trial participants. Traditionally, safety monitoring includes manual review and coding of adverse event data by expert clinicians.
OBJECTIVES:
Our study explores the use of natural language processing (NLP) and artificial intelligence (AI) methods to streamline and standardize clinician coding of adverse event data in Alzheimer's disease (AD) clinical trials.
DESIGN:
Our quantitative retrospective study aimed to develop a gold standard AD adverse event data set, evaluate the predictive performance of NLP-based models to classify adverse events, and determine whether automated coding is more efficient, accurate, reliable, and consistent than clinician coding.
SETTING:
Our study was conducted at the University of Southern California's Alzheimer's Therapeutic Research Institute (ATRI). ATRI serves as the clinical and data coordinating center for the Alzheimer's Clinical Trial Consortium (ACTC).
PARTICIPANTS:
We collected demographic and adverse event data from eight completed clinical trials in participants (n=1920) with symptomatic AD conducted between 2005 and 2020.
MEASUREMENTS:
Original expert clinician-confirmed codes were used for all model performance comparisons. F1 score was used as the primary model selection metric. Final classifier performance was evaluated using predictive accuracy. Clinician effort was measured in time to code, review, and confirm coded adverse events.
RESULTS:
In a sample of 1000 adverse events, AI-based AE coding achieved higher accuracy (∼20% increase in accuracy) and was more cost-effective (∼80% cost reduction) than traditional clinician coding.
CONCLUSIONS:
Our study results demonstrate how approaches that effectively combine AI and human expertise can improve the efficiency and quality of adverse event coding and clinical trial safety monitoring.
CITATION:
Gustavo A. Jimenez-Maggiora ; Michael C. Donohue ; Michael S. Rafii ; Rema Raman ; Paul S. Aisen (2025): Artificial intelligence-enabled safety monitoring in Alzheimer's disease clinical trials. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100002
PLASMA AMYLOID-Β PRECURSOR PROTEIN 669–711/AMYLOID-Β1–42 RATIO IS ASSOCIATED WITH COGNITION IN ALZHEIMER\'S DISEASE
Moeko Noguchi-Shinohara, Yasuhiro Sakashita, Hiroto Nakano, Daiki Muramatsu, Sadao Hikishima, Junji Komatsu, Hidetomo Murakami, Yukiko Mori, Kenjiro Ono
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryPlasma amyloid-β (Aβ) markers are significant predictors of Aβ pathology. However, their prognostic value for cognition in patients with Alzheimer's disease (AD) is unknown. We compared plasma amyloid-β precursor protein (APP)669–711 and Aβ1–42 levels between cognitively unimpaired participants (CU) and those with MCI due to AD and AD dementia. The CU group was divided into CU+ or CU- groups according to presence of Aβ pathology. All patients with AD exhibited Aβ pathology. The plasma APP669–711/Aβ1–42 ratio was significantly elevated in patients with CU+, MCI+, and AD+ compared with those with CU-. Furthermore, the plasma APP669–711/Aβ1–42 ratio was significantly correlated with the MMSE score (rs = −0.544, p < 0.001). Analysis of the Aβ+ group revealed that the significant relationship between MMSE score and plasma APP669–711/Aβ1–42 ratio remained unchanged (rs = −0.244, p = 0.027). Therefore, we conclude that the plasma APP669–711/Aβ1–42 ratio is associated with cognition in patients with AD.
CITATION:
Moeko Noguchi-Shinohara ; Yasuhiro Sakashita ; Hiroto Nakano ; Daiki Muramatsu ; Sadao Hikishima ; Junji Komatsu ; Hidetomo Murakami ; Yukiko Mori ; Kenjiro Ono (2025): Plasma amyloid-β precursor protein 669–711/amyloid-β1–42 ratio is associated with cognition in Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100003
INFORMING ETIOLOGICAL HETEROGENEITY OF MILD COGNITIVE IMPAIRMENT AND RISK FOR PROGRESSION TO DEMENTIA WITH PLASMA P-TAU217
Breton M. Asken, Rosie E. Curiel Cid, Elizabeth A. Crocco, Melissa J. Armstrong, Shellie-Anne Levy, Franchesca Arias, Monica Rosselli, Idaly Velez Uribe, Warren W. Barker, Emily F. Matusz, Jesse C. DeSimone, Wei-en Wang, Jacob Fiala, Michael M. Marsiske, Steven T. DeKosky, David E. Vaillancourt, Ranjan Duara, David A. Loewenstein, Glenn E. Smith
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
Mild cognitive impairment (MCI) is a clinical diagnosis representing early symptom changes with preserved functional independence. There are multiple potential etiologies of MCI. While often presumed to be related to Alzheimer's disease (AD), other neurodegenerative and non-neurodegenerative causes are common. Wider availability of relatively non-invasive plasma AD biomarkers, such as p-tau217, can provide invaluable insights into MCI clinico-pathology and the associated implications for symptom etiology, prognosis (e.g., risk for progression to dementia), and treatment options.
OBJECTIVES:
The main goal of this study was to evaluate differences between individuals with MCI with and without plasma p-tau217 biomarker evidence of AD (MCIAD+ and MCIAD-) as well as a control group of clinically normal older adults with negative AD biomarkers (CNAD-). We evaluated group differences in demographics, recruitment, clinical scales, fluid biomarkers, and brain imaging. We further probed these factors as independent contributors to symptoms among MCIAD- participants, for whom symptom etiology is most poorly understood. Lastly, in a subset of participants followed longitudinally, we investigated how these factors related to odds of clinical progression to dementia.
DESIGN:
We conducted an observational cross-sectional and longitudinal clinical research study. Study groups were compared cross-sectionally on demographics, recruitment, clinical measures, and biomarkers (chi square analyses, analyses of covariance). Contributors to functional changes were evaluated with multiple linear regression. Factors associated with the odds of progression from MCI to dementia longitudinally were evaluated with binary logistic regression.
SETTING:
1Florida Alzheimer's Disease Research Center.
PARTICIPANTS:
Cross-sectional analyses included 378 older adults classified as CNAD- (N = 76, age 66.1 ± 7.2, 63.2% female, 23.7% non-Hispanic/White), MCIAD- (N = 198, age 68.9 ± 7.9, 51.5% female, 29.3% non-Hispanic/White), or MCIAD+ (N = 104, age 73.9 ± 7.4, 52.9% female, 49.0% non-Hispanic/White). Longitudinal analyses focused on 207 participants with MCI (68.5% of cross-sectional MCI sample) followed for an average of 3 years.
MEASUREMENTS:
Demographics (age, sex, years of education, self-identified race and ethnicity, primary spoken language), National Alzheimer's Coordinating Center-defined clinical phenotypes (Clinically Normal, Impaired – Not MCI, Amnestic MCI, Nonamnestic MCI, Dementia), recruitment source (clinic-based versus community-based), genetics (APOE genotype), functional evaluation (Clinical Dementia Rating scale), global cognition (Mini Mental State Exam), vascular history (Vascular Burden Score), neuropsychiatric symptoms (NPI-Q Total score), plasma biomarkers (ALZPath p-tau217, Quanterix Simoa-based GFAP and NfL), and brain imaging (grey matter volume in select AD-relevant regions of interest, global white matter hyperintensity volume).
RESULTS:
Among those with MCI, 104 (34.4%) had plasma biomarker evidence of AD. MCIAD+ participants were more frequently recruited from clinic-based settings than MCIAD- (74.8% vs. 47.5%, p<.001). Over half (51.5%) of MCIAD+ carried at least one APOE e4 allele compared to 26.6% of MCIAD- and 29.4% of CNAD- (p<.001). Both MCIAD+ (p<.001, Cohen's d = 0.93) and MCIAD- (p<.001, d = 0.75) reported more severe neuropsychiatric symptoms than CNAD. MCIAD+ had higher plasma GFAP and NfL than both MCIAD- (GFAP: p<.001, d = 0.88, NfL: p<.001, d = 0.86) and CNAD- (GFAP: p<.001, d = 0.80; NfL: p<.001, d = 0.89). For the AD signature region of interest, MCIAD+ had lower volume than both CNAD- (p<.001, d = 0.78) and MCIAD- (p=.018, d = 0.39). For the hippocampus, both MCIAD+ (p<.001, d = 0.87) and MCIAD- (p<.001, d = 0.64) had lower volume than CNAD-. Longitudinally, older age (OR=1.14 [1.06–1.22], p<.001), higher levels of p-tau217 (OR=10.37 [3.00–35.02], p<.001) and higher neuropsychiatric symptoms (OR=1.19 [1.02–1.39], p=.023) were associated with higher odds of progression to dementia.
CONCLUSIONS:
MCI is etiologically heterogeneous. The presence of Alzheimer's pathology defined by elevated plasma p-tau217 in individuals with MCI significantly worsens prognosis. Neuropsychiatric symptoms may contribute to cognitive complaints and risk for progressive decline irrespective of AD pathology. Plasma p-tau217 can inform our understanding of base rates of different MCI phenotypes on a larger scale. As with other AD biomarkers, frequency of elevated plasma p-tau217 and odds of progression to dementia requires careful consideration of recruitment source (clinic- vs. community-based), especially across ethno-racially diverse older adults. Ongoing integration of emerging neurodegenerative disease biomarkers with detailed clinical evaluations will continue to improve treatment specificity and prognosis.
CITATION:
Breton M. Asken ; Rosie E. Curiel Cid ; Elizabeth A. Crocco ; Melissa J. Armstrong ; Shellie-Anne Levy ; Franchesca Arias ; Monica Rosselli ; Idaly Velez Uribe ; Warren W. Barker ; Emily F. Matusz ; Jesse C. DeSimone ; Wei-en Wang ; Jacob Fiala ; Michael M. Marsiske ; Steven T. DeKosky ; David E. Vaillancourt ; Ranjan Duara ; David A. Loewenstein ; Glenn E. Smith (2025): Informing etiological heterogeneity of mild cognitive impairment and risk for progression to dementia with plasma p-tau217. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100011
MAINTAINING LEVEL OF MODIFIABLE DEMENTIA RISK SCORES IS ASSOCIATED WITH BETTER COGNITIVE OUTCOMES THAN INCREASING RISK SCORES: A POPULATION-BASED PROSPECTIVE COHORT STUDY
Stephanie Van Asbroeck, Md Hamidul Huque, Scherazad Kootar, Ruth Peters, Nicolas Cherbuin, Moyra E Mortby, Sebastian Köhler, Martin PJ van Boxtel, Kay Deckers, Kaarin J Anstey
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
A brain healthy lifestyle, consisting of good cardiometabolic health and being cognitively and socially active in midlife, is associated with a lower risk of cognitive decline years later. However, it is unclear whether lifestyle changes over time also affect the risk for mild cognitive impairment (MCI)/dementia, and rate of cognitive decline.
OBJECTIVES:
To investigate if lifestyle changes over time are associated with incident MCI/dementia risk and rate of cognitive decline.
DESIGN:
Population-based prospective cohort study
SETTING:
Personality and Total Health (PATH) Through Life Study cohort (Australia).
PARTICIPANTS:
4,777 participants (50.4% women), recruited between 2000 and 2002, who were 40–44 and 60–64 years old at baseline, without a prevalent dementia diagnosis. Participants had to have cognitive outcome measures available after baseline.
MEASUREMENTS:
Various measurements (neurocognitive assessment, blood pressure) and survey responses (demographics, cognitive, social, and physical activity, smoking, alcohol consumption, body height and weight, depression, and previous diagnoses) were collected approximately every four years. A brain-healthy lifestyle was operationalized via two well-validated modifiable dementia risk scores, the LIfestyle for BRAin health (LIBRA) score and the modifiable part of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRImod). Their change over time was estimated using latent growth curve modelling, and their association with cognition and incidence of MCI/dementia was investigated using parallel process modelling and Cox regression analysis.
RESULTS:
Within those aged 60–64 years at baseline (n=2,409), 211 cases of incident MCI/dementia were recorded over a median follow-up time of 12.2 years. On average, individuals’ LIBRA and ANU-ADRImod increased (i.e., worsened) over time, but individuals whose scores increased one standard deviation (SD) less had a 19.0–24.6% lower risk for MCI/dementia (hazard ratio (95% confidence interval): LIBRAchange over time=0.754 (0.664–0.857), ANU-ADRImod, change over time=0.810 (0.71–0.915)), while controlling for the risk score at baseline and multiple potential confounders. Various associations between dementia risk score trajectories and cognitive performance trajectories were observed.
CONCLUSIONS
Efforts to maintain a brain healthy lifestyle could reduce the risk for MCI or dementia, and slow cognitive decline.
CITATION:
Stephanie Van Asbroeck ; Md Hamidul Huque ; Scherazad Kootar ; Ruth Peters ; Nicolas Cherbui ; Moyra E Mortby ; Sebastian Köhler ; Martin PJ van Boxtel ; Kay Deckers ; Kaarin J Anstey (2025): Maintaining level of modifiable dementia risk scores is associated with better cognitive outcomes than increasing risk scores: A population-based prospective cohort study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100014
CARDIOVASCULAR HEALTH, GENETIC PREDISPOSITION, AND DEMENTIA RISK AMONG ATHEROSCLEROTIC CARDIOVASCULAR DISEASE PATIENTS
Lingyan Dai, Chunxiang Jiang, Qingmei Cui, Leen Huang, Siqi Chen, Yidan Zhang, Xiaoyi Luo, Piao Zhang, Jie Li, Yuhu Zhang
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
While optimal cardiovascular health (CVH) has been linked to a lower risk of dementia, few studies considered individuals' genetic background. We aimed to examine the interaction between CVH and genetic predisposition on dementia risk among individuals with atherosclerotic cardiovascular disease (ASCVD).
METHODS:
We included 30,818 ASCVD patients from the UK Biobank. CVH was assessed using Life's Essential 8, and genetic predisposition determined by a genetic risk score (GRS) incorporating 85 genetic variants. Cox proportional hazard models were used to estimate hazard ratios (HRs) for all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD).
RESULTS:
Over a median follow-up of 13.5 years, 1,360 cases of all-cause dementia were identified, including 489 AD and 440 VaD cases. Higher CVH levels were associated with a reduced risk of all-cause dementia (HR for high vs. low CVH: 0.60; 95 % CI: 0.47–0.77) and VaD (HR for high vs. low CVH: 0.32; 95 % CI: 0.19–0.54), with a stronger association in individuals with lower GRS. Although the overall CVH score was not associated with the risk of dementia in individuals with high GRS, higher levels of sleep and glucose control were associated with a lower risk of VaD. CVH levels showed no association with the risk of AD.
CONCLUSIONS:
Higher CVH levels were associated with a lower risk of VaD, not AD, with a stronger association in individuals with low GRS. Improvements in specific LE8 components, particularly sleep health and blood glucose management, were associated with reduced VaD risk across various genetic risk strata.
CITATION:
Lingyan Dai ; Chunxiang Jiang ; Qingmei Cui ; Leen Huang ; Siqi Chen ; Yidan Zhang ; Xiaoyi Luo ; Piao Zhang ; Jie Li ; Yuhu Zhang (2025): Cardiovascular health, genetic predisposition, and dementia risk among atherosclerotic cardiovascular disease patients. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100020
THE IMPACT OF HYPERTENSION PREVENTION AND MODIFICATION ON DEMENTIA BURDEN: A SYSTEMATIC REVIEW OF ECONOMIC STUDIES
Marie Lan, Ava John-Baptiste, Cassandra Curran, Feben W. Alemu, Abolfazl Avan, Kelly K. Anderson, Shehzad Ali
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryAIM:
Neurological disorders account for the largest proportion of disability-adjusted life years globally, with dementia being the third leading cause. Hypertension has been identified as a priority, targetable risk factor for dementia. This study aimed to systematically review economic studies that examine the impact of hypertension prevention and control on the costs and outcomes of dementia.
METHODS:
An electronic literature search was conducted using MEDLINE, EMBASE, Scopus, Web of Science, EconLit, and grey literature sources. The inclusion criteria were: 1) economic evaluation studies, including both full and partial evaluations; 2) a primary focus on dementia; and 3) evaluation of the impact of preventing or modifying hypertension on the burden of dementia. The quality of included studies was assessed using the Consensus on Health Economic Criteria (CHEC) list.
RESULTS:
Twelve studies were included in the final review. Four studies were full economic evaluations, while eight were partial evaluations, with one reporting costs and seven reporting the impact on dementia prevalence. Nine studies considered hypothetical reductions in hypertension rate, while three evaluated applied hypertension-related interventions. Hypertension modification was associated with higher life expectancy and a higher average age of dementia onset. Full economic evaluations of specific hypertension modification interventions found that these interventions dominated (i.e. had lower costs and higher quality-adjusted life-years (QALY)) the status quo scenario or had an acceptable incremental cost-effectiveness ratio (ICER).
CONCLUSIONS:
Hypertension modification has the potential to reduce the burden of dementia in a cost-effective way. However, further economic evaluations of applied interventions are needed to determine real-world feasibility and cost-effectiveness.
CITATION:
Marie Lan ; Ava John-Baptiste ; Cassandra Curran ; Feben W. Alemu ; Abolfazl Avan ; Kelly K. Anderson ; Shehzad Ali (2025): The impact of hypertension prevention and modification on dementia burden: A systematic review of economic studies. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100017
DIETARY SUPPLEMENTATION AND THE ROLE OF PHYTOCHEMICALS AGAINST THE ALZHEIMER\'S DISEASE: FOCUS ON POLYPHENOLIC COMPOUNDS
Rayees Ahmad Naik, Roshni Rajpoot, Raj Kumar Koiri, Rima Bhardwaj, Abdullah F. Aldairi, Ayman K. Johargy, Hani Faidah, Ahmad O. Babalghith, Ahmed Hjazi, Walaa F. Alsanie, Abdulhakeem S. Alamri, Majid Alhomrani, Abdulaziz Alsharif, Anastasiia Shkodina, Sandeep Kumar Singh
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryAlzheimer's disease is a complicated, multifaceted, neurodegenerative illness that places an increasing strain on healthcare systems. Due to increasing malfunction and death of nerve cells, the person suffering from Alzheimer's disease (AD) slowly and steadily loses their memories, cognitive functions and even their personality. Although medications may temporarily enhance memory, there are currently no permanent therapies that can halt or cure this irreversible neurodegenerative process. Nonetheless, fast progress in comprehending the cellular and molecular abnormalities responsible for neuronal degeneration has increased confidence in the development of viable prevention and treatments. All FDA-approved anti-AD medications have merely symptomatic effects and cannot cure the illness. This necessitates the pursuit of alternate treatments. Accumulating data shows that systemic neuroinflammation, oxidative stress and associated mitochondrial dysfunction play crucial roles in the etiology of AD and precede its clinical presentation. Therefore, innovative therapeutic approaches targeting these pathophysiological components of Alzheimer's disease are being explored aggressively in the present scenario. Phytochemicals such as resveratrol, curcumin, quercetin, genistein and catechins are prospective therapies owing to their capacity to alter key AD pathogenetic pathways, such as oxidative stress, neuroinflammation, and mitochondrial dysfunction. The use of new phytochemical delivery strategies would certainly provide the possibility to solve several issues with standard anti-AD medicines. In this review, the roles of phytophenolic compound-based treatment strategies for AD are discussed.
CITATION:
Rayees Ahmad Naik ; Roshni Rajpoot ; Raj Kumar Koiri ; Rima Bhardwaj ; Abdullah F. Aldairi ; Ayman K. Johargy ; Hani Faidah ; Ahmad O. Babalghith ; Ahmed Hjazi ; Walaa F. Alsanie ; Abdulhakeem S. Alamri ; Majid Alhomrani ; Abdulaziz Alsharif ; Anastasiia Shkodina ; Sandeep Kumar Singh (2025): Dietary supplementation and the role of phytochemicals against the Alzheimer's disease: Focus on polyphenolic compounds. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100004
GENETIC PREDISPOSITION TO HIGH CIRCULATING LEVELS OF INTERLEUKIN 6 AND RISK FOR ALZHEIMER\'S DISEASE. DISCOVERY AND REPLICATION
Sokratis Charisis, Niki Mourtzi, Matthew R. Scott, Eva Ntanasi, Eirini Mamalaki, Alexandros Hatzimanolis, Alfredo Ramirez, Jean-Charles Lambert, Mary Yannakoulia, Mary Kosmidis, Efthimios Dardiotis, Georgios Hadjigeorgiou, Paraskevi Sakka, Claudia L Satizabal, Alexa Beiser, Qiong Yang, Marios ?. Georgakis, Sudha Seshadri, Nikolaos Scarmeas
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryIMPORTANCE:
Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.
OBJECTIVE:
To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.
DESIGN:
We analyzed data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Mean follow-up was 2.9 (SD, 0.8) years. Baseline assessment was from 11/2009 to 11/2016, and cognitive follow-up from 01/2013 to 07/2019. Associations of interest were also examined in the UK Biobank (UKB) for replication purposes (mean follow-up was 12.9 (SD, 2.4) years; baseline assessment was from 12/2006 to 10/2010).
SETTING:
Population-based study.
PARTICIPANTS:
The HELIAD sample included 622 participants ≥65 years of age without baseline dementia or amnestic mild cognitive impairment (aMCI-the prodromal stage of AD). The UKB sample included 142,637 participants ≥60 years of age without prevalent dementia.
EXPOSURES:
Genetic predisposition to elevated circulating levels of IL-6 was estimated using a polygenic risk score (PRS), calculated based on the summary statistics of a current GWAS meta-analysis.
MAIN OUTCOMES AND MEASURES:
AD and MCI diagnoses were based on standard clinical criteria [HELIAD], or hospital records and death registry data [UKB]. Associations with AD or aMCI incidence [HELIAD] and AD incidence [UKB] were examined with Cox regression models.
RESULTS:
In HELIAD, mean age was 73.4 (SD, 5.0) years; 363 (58%) women. An increase in IL-6 PRS by 1 standard deviation unit (SDU) was associated with up to a 43% increase in the risk for incident AD/aMCI (HRGWAS significance threshold of 0.01, 1.43 [95%CI, 1.14 – 1.80]). In UKBB, mean age was 64.2 (SD, 2.8) years; 73,707 (52%) women. A 1 SDU increase in IL-6 PRS was associated with up to an 8% increase in the risk for incident AD (HRGWAS significance threshold of 0.2, 1.08 [95%CI, 1.04 – 1.12]).
CONCLUSIONS AND RELEVANCE:
Genetic predisposition to higher circulating levels of IL-6 was associated with an increased risk for AD, supporting the role of IL-6-related pathways in AD pathogenesis, and suggesting that genetic predisposition to proinflammatory states might trigger or accelerate AD-related neuropathology.
CITATION:
Sokratis Charisis ; Niki Mourtzi ; Matthew R. Scott ; Eva Ntanasi ; Eirini Mamalaki ; Alexandros Hatzimanolis ; Alfredo Ramirez ; Jean-Charles Lambert ; Mary Yannakoulia ; Mary Kosmidis ; Efthimios Dardiotis ; Georgios Hadjigeorgiou ; Paraskevi Sakka ; Claudia L Satizabal ; Alexa Beiser ; Qiong Yang ; Marios Κ. Georgakis ; Sudha Seshadri ; Nikolaos Scarmeas (2025): Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100018
LIVER FUNCTION AND ALZHEIMER\'S BRAIN PATHOLOGIES: A LONGITUDINAL STUDY: LIVER AND ALZHEIMER\'S PATHOLOGIES
Jee Wook Kim, Min Soo Byun, Dahyun Yi, Joon Hyung Jung, Nayeong Kong, Yoon Young Chang, Gijung Jung, Hyejin Ahn, Jun-Young Lee, Koung Mi Kang, Chul-Ho Sohn, Yun-Sang Lee, Yu Kyeong Kim, Dong Young Lee, for the KBASE Research Group
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryIMPORTANCE:
The neuropathological links underlying the association between changes in liver function and AD have not yet been clearly elucidated.
OBJECTIVE:
We aimed to examine the relationship between liver function markers and longitudinal changes in Alzheimer's disease (AD) core pathologies.
DESIGN:
Data from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a longitudinal cohort study initiated in 2014, were utilized.
SETTING:
Community and memory clinic setting.
PARTICIPANTS:
Three hundred forty-seven older adults.
MAIN OUTCOME AND MEASURES:
Participants underwent baseline and 2-year follow-up evaluations, including liver function assessments and various brain imaging techniques, such as amyloid and tau PET, FDG-PET, and MRI). Liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin] were examined as exposure variables.
RESULTS:
Higher baseline ALT levels were associated with a greater increase in beta-amyloid deposition over 2 years [β = 0.166, Bonferroni-corrected P (PB) = 0.012], while lower total bilirubin levels were associated with a greater increase in tau deposition over the same period (β = -0.570, PB < 0.001). In contrast, AST alone showed no significant association with changes of AD pathologies.
CONCLUSIONS AND RELEVANCE:
The findings suggest a possible link between lower liver function and the accumulation of core AD pathologies in the brain. These results also support the possibility that the liver-brain axis could be a potential target for therapeutic or preventive strategies against AD.
CITATION:
Jee Wook Kim ; Min Soo Byun ; Dahyun Yi ; Joon Hyung Jung ; Nayeong Kong ; Yoon Young Chang ; Gijung Jung ; Hyejin Ahn ; Jun-Young Lee ; Koung Mi Kang ; Chul-Ho Sohn ; Yun-Sang Lee ; Yu Kyeong Kim ; Dong Young Lee ; for the KBASE Research Group 1 (2025): Liver function and Alzheimer's brain pathologies: A longitudinal study: Liver and Alzheimer's pathologies. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100012
MICROGLIAL ACTIVATION STATES AND THEIR IMPLICATIONS FOR ALZHEIMER\'S DISEASE
Zachary Valiukas, Kathy Tangalakis, Vasso Apostolopoulos, Jack Feehan
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryAlzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) of tau protein in the brain. Microglia, key immune cells of the central nervous system, play an important role in AD development and progression, primarily through their responses to Aβ and NFTs. Initially, microglia can clear Aβ, but in AD, chronic activation overwhelms protective mechanisms, leading to sustained neuroinflammation that enhances plaque toxicity, setting off a damaging cycle that affects neurons, astrocytes, cerebral vasculature, and other microglia. Current AD treatments have been largely ineffective, though emerging immunotherapies focusing on plaque removal show promise, but often overlook the role of neuroinflammation. Activated microglia display a complex range of phenotypes that can be broadly broken into pro- or anti-inflammatory states, although this dichotomy does not describe the significant overlap between states. Aβ can strongly induce inflammatory activity, triggering the production of reactive oxygen species, inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6), synapse engulfment, blood-brain barrier compromise, and impaired Aβ clearance. These processes contribute to neural tissue loss, manifesting as cognitive decline such as impaired executive function and memory. Conversely, anti-inflammatory activation exerts neuroprotective effects by suppressing inflammatory pathways and releasing neurotrophic factors that aid neuron repair and protection. Induction of anti-inflammatory states may offer a dual therapeutic approach to address both neuroinflammation and plaque accumulation in AD. This approach suggests potential strategies to modulate microglial phenotypes, aiming to restore neuroprotective functions and mitigate disease progression by simultaneously targeting inflammation and plaque pathology.
CITATION:
Zachary Valiukas ; Kathy Tangalakis ; Vasso Apostolopoulos ; Jack Feehan (2025): Microglial activation states and their implications for Alzheimer's Disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100013
MOTOR ABILITIES AND COGNITIVE PERFORMANCE IN LATINOS WITH AUTOSOMAL DOMINANT ALZHEIMER\'S DISEASE
Andrew J. Petkus, Anup N. Sonti, Lucy Montoya, Abhay Sagare, John M. Ringman, Andrew J. Petkus, Anup N. Sonti, Lucy Montoya, Abhay Sagare, John M. Ringman
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
Declining motor abilities might be a noninvasive biomarker for Alzheimer's disease (AD). Studying motor ability and AD progression in younger Latinos with autosomal dominant Alzheimer's disease (ADAD) can provide insights into the interplay between motor ability and cognition in individuals with minimal confounding from age-normative changes and comorbid medical conditions.
OBJECTIVES:
This study aimed to (1) examine motor abilities as a function of years to dementia diagnosis and (2) examine associations between motor ability and cognitive performance.
DESIGN:
This was a cross-sectional observational study.
SETTING:
The study took place at the University of Southern California.
PARTICIPANTS:
39 predominately Latino individuals (mean age 38.6 ± 10 years old) known to carry (carriers; n=25) or be at 50% risk for inheriting ADAD but not carrying the mutation (noncarriers; n=14).
MEASUREMENTS:
Individuals completed the motor and cognitive batteries from the National Institute of Health Toolbox (NIHTB) and the Cognitive Abilities Screening Instrument (CASI). All models included effects for age, education, primary language, and sex.
RESULTS:
Compared to noncarriers, ADAD mutation carriers had significantly weaker grip strength at 12 years, worse manual dexterity at 10 years, and slower gait speed seven years before the expected age of dementia diagnosis. Worse motor ability was associated with a more severe cognitive disease stage and worse CASI performance, adjusting for demographic and clinical variables.
CONCLUSIONS:
The findings support the utility of motor performance, precisely grip strength, manual dexterity, and gait speed as potential biomarkers of preclinical AD.
CITATION:
Andrew J. Petkus ; Anup N. Sonti ; Lucy Montoya ; Abhay Sagare ; John M. Ringman (2025): Motor abilities and cognitive performance in Latinos with autosomal dominant Alzheimer's disease. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100010
USEFULNESS OF CEREBROSPINAL FLUID ALZHEIMER\'S DISEASE BIOMARKERS IN OLDER PATIENTS: EVIDENCE FROM A NATIONAL MULTICENTER PROSPECTIVE STUDY
Théodore Decaix, François Mouton-Liger, Julien Dumurgier, Emmanuel Cognat, Agathe Vrillon, Jacques Hugon, Claire Hourregue, Elodie Bouaziz-Amar, David Wallon, Muriel Quillard Muraine, Anne-Cécile Troussière, Eloi Magnin, Emmanuelle Duron, Nathalie Philippi, Frédéric Blanc, Audrey Gabelle, Bernard Croisile, Alain Jager, Florence Pasquier, Susanna Schraen, Matthieu Lilamand
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryBACKGROUND:
The use of cerebrospinal (CSF) biomarkers in the diagnosis of Alzheimer's disease (AD) has been gaining interest in clinical practice. Although their usefulness has been demonstrated, their potential value in older patients remains debated.
OBJECTIVES:
To assess whether knowledge of the results of CSF AD biomarkers was associated with the same gain in diagnostic confidence in older adults > 80 than in younger patients.
DESIGN:
Prospective multicenter study, including memory clinics physicians who completed a two-part questionnaire for all their patients addressing the requirement for assessment of Alzheimer's disease biomarkers in CSF proposed as part of routine care during the study period.
SETTING:
30 secondary or tertiary memory clinics in France.
MEASUREMENTS:
Clinicians indicated their diagnosis hypothesis and an estimate of their diagnostic confidence [scale 1–10]. Receiver operating characteristic (ROC) analysis, including the calculation of the area under the curve (AUC), was conducted using logistic regression to evaluate the diagnostic performance of CSF AD biomarkers.
RESULTS:
In 813 consecutive patients, median age 70 [interquartile range (IQR) = 63 – 77] including 132 patients over 80 years, we observed a similar confidence gain in CSF biomarkers between older and younger patients, both for AD and non-AD diagnoses. In older patients, the added value of CSF biomarkers was greater when CSF biomarkers indicated AD profile whereas the initial hypothesis was “non-AD”, leading to a final diagnosis of AD (2.4 ± 1.6 versus 1.1 ± 2.1, p-value, p = 0.03). ROC analyses showed similar performance of AD CSF biomarkers in older and younger patients.
CONCLUSION:
CSF AD biomarkers added substantial value to clinical assessment in patients over 80. Their use seems crucial in the diagnostic process for older adults referred to memory clinics.
CITATION:
Théodore Decaix ; François Mouton-Liger ; Julien Dumurgier ; Emmanuel Cognat ; Agathe Vrillon ; Jacques Hugon ; Claire Hourregue ; Elodie Bouaziz-Amar ; David Wallon ; Muriel Quillard Muraine ; Anne-Cécile Troussière ; Eloi Magnin ; Emmanuelle Duron ; Nathalie Philippi ; Frédéric Blanc ; Audrey Gabelle ; Bernard Croisile ; Alain Jager ; Florence Pasquier ; Susanna Schraen ; Matthieu Lilamand (2025): Usefulness of Cerebrospinal Fluid Alzheimer's disease biomarkers in older patients: Evidence from a national multicenter prospective study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100009
INFORMAL CARE FOR PEOPLE WITH DEMENTIA IN EUROPE
Ron Handels, Somboon Hataiyusuk, Anders Wimo, Anders Sköldunger, Christian Bakker, Anja Bieber, Alfonso Ciccone, Carlo Alberto Defanti, Andrea Fabbo, Sara Fascendini, Lutz Frölich, Chloé Gervès-Pinquié, Manuel Gonçalves-Pereira, Kate Irving, Raymond Koopmans, Patrizia Mecocci, Paola Merlo, Bernhard Michalowsky, Oliver Peters, Yolande Pijnenburg, Linus Jönsson
J Prev Alz Dis 2025;1(12)
Show summaryHide summaryINTRODUCTION:
Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.
METHODS:
A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia. A mixed regression model was fitted to time spent on instrumental or basic activities of daily living using disease severity and demographic characteristics.
RESULTS:
Daily informal care time was 0.5 hours higher in moderate compared to mild and 1.3h higher in severe compared to mild cognitive impairment. Likewise, this was 1.2h and 2.7h for functional disability and 0.3h and 0.6h for behavioral symptoms in the same directions.
DISCUSSION:
Estimates can be used in both single- and multi-domain health-economic models for dementia in European settings.
CITATION:
Ron Handels ; Somboon Hataiyusuk ; Anders Wimo ; Anders Sköldunger ; Christian Bakker ; Anja Bieber ; Alfonso Ciccone ; Carlo Alberto Defanti ; Andrea Fabbo ; Sara Fascendini ; Lutz Frölich ; Chloé Gervès-Pinquié ; Manuel Gonçalves-Pereira ; Kate Irving ; Raymond Koopmans ; Patrizia Mecocci ; Paola Merlo ; Bernhard Michalowsky ; Oliver Peters ; Yolande Pijnenburg ; Linus Jönsson (2025): Informal care for people with dementia in Europe. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2024.100015