Alzheimer's Research & Therapy最新文献

{"title":"Frequency, sociodemographic, and neuropsychological features of patients with subjective cognitive decline diagnosed using different neuropsychological criteria.","authors":"Pedro Câmara Pestana, Sandra Cardoso, Manuela Guerreiro, João Maroco, Frank Jessen, Frederico Simões do Couto, Alexandre de Mendonça","doi":"10.1186/s13195-024-01634-1","DOIUrl":"10.1186/s13195-024-01634-1","url":null,"abstract":"<p><strong>Background: </strong>Subjective Cognitive Decline (SCD) is recognized as a risk stage for future cognitive impairment and dementia. The criteria for SCD include normal performance on neuropsychological testing; however, there is a lack of consensus regarding standard score cut-offs for neuropsychological tests to define cognitive impairment and to differentiate between SCD and Mild Cognitive Impairment (MCI). This study aimed to assess the frequency of SCD diagnosis using various neuropsychological definitions of cognitive normality and to characterize the sociodemographic and neuropsychological features of SCD patients diagnosed under these criteria.</p><p><strong>Methods: </strong>The Cognitive Complaints Cohort (CCC) participants were diagnosed following Subjective Cognitive Decline Initiative (SCD-I) criteria. Normal cognitive performance was defined by the absence of Mild Cognitive Impairment (MCI) according to the five sets of MCI neuropsychologically based criteria defined by Jak and Bondi. Descriptive statistics were used to analyze sociodemographic, clinical, and neuropsychological data. A bootstrap methodology was employed to estimate the mean and 95% confidence intervals (CI) for specific parameters of interest, namely the SMC scale (subjective memory complaints scale), Mini-Mental State Examination (MMSE), Blessed Dementia Rating Scale - first part (BDRS first part), and Geriatric Depression Scale (GDS).</p><p><strong>Results: </strong>Among the 1268 subjects included, the prevalence of SCD diagnosis exhibited substantial variation across SCD-I criteria using different neuropsychological definitions of cognitive normality (ranging from 16.4 to 81.3%). When using the most conservative criteria to define cognitive impairment (2 tests within a cognitive domain > 1.5 SD below age-adjusted means), the resulting Conservative SCD group had poorer global cognitive function (MMSE: mean 27.15, 95% CI 27.00-27.31), whereas when using the most liberal criteria to define cognitive impairment (only one test > 1 SD below age-adjusted means) the resulting Liberal SCD group had superior performance in daily-life functioning (BDRS first part: mean 0.30, 95% CI 0.23-0.38). However, subjective cognitive complaints and neuropsychiatric symptoms did not significantly differ among SCD diagnostic groups.</p><p><strong>Conclusions: </strong>The utilization of diagnostic criteria using distinct neuropsychological definitions of cognitive normality significantly impacts the frequency of SCD diagnosis and characterizes different patient populations. Consequently, it is essential to specify the criterion when diagnosing a SCD patient and to understand the risks and benefits of using different criteria to define cognitive impairment.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"261"},"PeriodicalIF":7.9,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Different associations between body mass index and Alzheimer's markers depending on metabolic health.","authors":"Eun Hye Lee, Heejin Yoo, Young Ju Kim, Bo Kyoung Cheon, Seungho Ryu, Yoosoo Chang, Jihwan Yun, Hyemin Jang, Jun Pyo Kim, Hee Jin Kim, Seong-Beom Koh, Jee Hyang Jeong, Duk L Na, Sang Won Seo, Sung Hoon Kang","doi":"10.1186/s13195-024-01625-2","DOIUrl":"https://doi.org/10.1186/s13195-024-01625-2","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"260"},"PeriodicalIF":7.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway.","authors":"Kyonghwan Choe, Muhammad Ali, Roy Lardenoije, Renzo J M Riemens, Ehsan Pishva, Horst Bickel, Siegfried Weyerer, Per Hoffmann, Michael Pentzek, Steffi Riedel-Heller, Birgitt Wiese, Martin Scherer, Michael Wagner, Diego Mastroeni, Paul D Coleman, Alfredo Ramirez, Inez H G B Ramakers, Frans R J Verhey, Bart P F Rutten, Gunter Kenis, Daniel L A van den Hove","doi":"10.1186/s13195-024-01623-4","DOIUrl":"https://doi.org/10.1186/s13195-024-01623-4","url":null,"abstract":"<p><strong>Background: </strong>Neurodegenerative disorders, including Alzheimer's disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts.</p><p><strong>Methods: </strong>DNA derived from post-mortem middle temporal gyrus (MTG) tissue from AD patients (n = 45) and age-matched controls (n = 35) was analyzed, along with DNA derived from blood samples from two independent cohorts: the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) cohort (n = 96) and the Dutch BioBank Alzheimer Center Limburg (BBACL) cohort (n = 262). Molecular profiling, including assessing mRNA expression and DNA (hydroxy)methylation levels, was conducted using HumanHT-12 v4 Expression BeadChip and HM 450 K BeadChip arrays, respectively. Functional interactions between genes and identification of common phenotype-specific positive and negative elementary circuits were conducted using computational modeling, i.e. gene regulatory network (GRN) and network perturbational analysis. DNA methylation of IDO2 (cg11251498) was analyzed using pyrosequencing.</p><p><strong>Results: </strong>Twelve TRP- and twenty NAD-associated genes were found to be differentially expressed in the MTG of AD patients. Gene sets associated in the kynurenine pathway, the most common TRP pathway, and NAD pathway, showed enrichment at the mRNA expression level. Downstream analyses integrating data on gene expression, DNA (hydroxy)methylation, and AD pathology, as well as GRN and network perturbation analyses, identified IDO2, an immune regulatory gene, as a key candidate in AD. Notably, one CpG site in IDO2 (cg11251498) exhibited significant methylation differences between AD converters and non-converters in the AgeCoDe cohort.</p><p><strong>Conclusion: </strong>These findings reveal substantial transcriptional and epigenetic alterations in TRP- and NAD-pathway-associated genes in AD, highlighting IDO2 as a key candidate gene for further investigation. These genes and their encoded proteins hold potential as novel biomarkers and therapeutic targets for AD.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"259"},"PeriodicalIF":7.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Glymphatic inhibition exacerbates tau propagation in an Alzheimer's disease model.","authors":"Douglas M Lopes, Jack A Wells, Da Ma, Lauren Wallis, Daniel Park, Sophie K Llewellyn, Zeshan Ahmed, Mark F Lythgoe, Ian F Harrison","doi":"10.1186/s13195-024-01624-3","DOIUrl":"10.1186/s13195-024-01624-3","url":null,"abstract":"","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"258"},"PeriodicalIF":7.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Head-to-head comparison of tau PET tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort.","authors":"Matteo Tonietto, Oscar Sotolongo-Grau, Núria Roé-Vellvé, Santiago Bullich, Juan Pablo Tartari, Ángela Sanabria, Ainhoa García-Sánchez, Edilio Borroni, Christopher Galli, Esther Pérez-Martínez, Joan Castell-Conesa, Isabel Roca, Lluís Tárraga, Agustín Ruiz, Andrew W Stephens, Mercè Boada, Gregory Klein, Marta Marquié","doi":"10.1186/s13195-024-01622-5","DOIUrl":"10.1186/s13195-024-01622-5","url":null,"abstract":"<p><strong>Background: </strong>Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 in the early stages of the AD continuum.</p><p><strong>Methods: </strong>Data from the TAU-PET FACEHBI clinical trial (EUDRA-CT 2021-000473-83) were analyzed. All participants were non-demented and underwent tau imaging with [¹⁸F]PI-2620 and [¹⁸F]RO948 PET within 3 months, amyloid imaging with [¹⁸F]Florbetaben and brain magnetic resonance imaging. Tau PET standardized uptake values ratios (SUVR) were calculated in Braak and typical off-target regions using the inferior cerebellar cortex as a reference region.</p><p><strong>Results: </strong>The cohort consisted of 18 individuals with subjective cognitive decline (n = 13) and mild cognitive impairment (n = 5), with centiloid values ranging from 17 to 159. Both tau tracers showed similar tau pathology distribution but presented a distinct off-target signal pattern on visual read. SUVR measurements for [¹⁸F]PI-2620 and [¹⁸F]RO948 were highly correlated in all Braak regions (R² range [0.65-0.80]). Regarding off-target signal, [¹⁸F]PI-2620 had higher SUVRs in vascular structures, and [¹⁸F]RO948 had higher SUVRs in the skull/meninges.</p><p><strong>Conclusions: </strong>In a cohort of individuals at early stages of the AD continuum, tau PET tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 showed similar in-vivo uptake in all Braak regions and distinct off-target signal. These preliminary results support the development of standardized quantification scales for tau deposition that are tracer-independent.</p><p><strong>Trial registration: </strong>AEMPS EudraCT 2021-000473-83. Registered 30 December 2021.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"257"},"PeriodicalIF":7.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computerized decision support to optimally funnel patients through the diagnostic pathway for dementia.","authors":"Aniek M van Gils, Antti Tolonen, Argonde C van Harten, Sinthujah Vigneswaran, Frederik Barkhof, Leonie N C Visser, Juha Koikkalainen, Sanna-Kaisa Herukka, Steen Gregers Hasselbalch, Patrizia Mecocci, Anne M Remes, Hilkka Soininen, Afina W Lemstra, Charlotte E Teunissen, Linus Jönsson, Jyrki Lötjönen, Wiesje M van der Flier, Hanneke F M Rhodius-Meester","doi":"10.1186/s13195-024-01614-5","DOIUrl":"10.1186/s13195-024-01614-5","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.</p><p><strong>Methods: </strong>We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer's disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN). Tests included digital cognitive screening (cCOG), neuropsychological and functional assessment (NP), MRI with automated quantification, and CSF biomarkers. Sequential testing followed a predetermined order, guided by diagnostic certainty. Diagnostic certainty was determined using a clinical decision support system (CDSS) that generates a disease state index (DSI, 0-1), indicating the probability of the syndrome diagnosis or underlying etiology. Diagnosis was confirmed if the DSI exceeded a predefined threshold based on sensitivity/specificity cutoffs relevant to each clinical scenario. Diagnostic accuracy and the need for additional testing were assessed at each step.</p><p><strong>Results: </strong>Using cCOG as a prescreener for 1) syndrome diagnosis has the potential to accurately reduce the need for extensive NP (42%), resulting in syndrome diagnosis in all patients, with a diagnostic accuracy of 0.71, which was comparable to using NP alone. For 2) etiological diagnosis, stepwise testing resulted in an etiological diagnosis in 80% of patients with a diagnostic accuracy of 0.77, with MRI needed in 77%, and CSF in 37%. When 3) determining DMT eligibility, stepwise testing (100% cCOG, 83% NP, 75% MRI) selected 60% of the patients for confirmatory CSF testing and eventually identified 90% of the potentially eligible patients with AD dementia.</p><p><strong>Conclusions: </strong>Different diagnostic pathways are accurate and efficient depending on the setting. As such, a data-driven tool holds promise for assisting clinicians in selecting tests of added value across different clinical contexts. This becomes especially important with DMT availability, where the need for more efficient diagnostic pathways is crucial to maintain the accessibility and affordability of dementia diagnoses.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"256"},"PeriodicalIF":7.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer's disease, positive for plasma p-tau217.","authors":"Branislav Kovacech, Nicholas C Cullen, Petr Novak, Jozef Hanes, Eva Kontsekova, Stanislav Katina, Vojtech Parrak, Michal Fresser, Jeroen Vanbrabant, Howard H Feldman, Bengt Winblad, Erik Stoops, Eugeen Vanmechelen, Norbert Zilka","doi":"10.1186/s13195-024-01620-7","DOIUrl":"10.1186/s13195-024-01620-7","url":null,"abstract":"<p><strong>Background: </strong>The spread of tau pathology closely correlates with the disease course and cognitive decline in Alzheimer's disease (AD). Tau-targeting immunotherapies are being developed to stop the spread of tau pathology and thus halt disease progression. In this post hoc analysis of the ADAMANT clinical trial, we examined the performance of AADvac1, an active immunotherapy targeting the microtubule-binding region (MTBR) of tau, in a subgroup of participants with elevated plasma p-tau217, indicating AD-related neuropathological changes.</p><p><strong>Methods: </strong>ADAMANT was a 24-month, randomized, placebo-controlled, parallel-group, double-blinded, multicenter, phase 2 clinical trial in subjects with mild AD. The trial participants were randomized 3:2 to receive six doses of AADvac1 or placebo at 4-week intervals, followed by five booster doses at 14-week intervals. The primary outcome was safety. The secondary outcomes were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer's Disease Cooperative Study - Activities of Daily Living score for Mild Cognitive Impairment 18-item version (ADCS-ADL-MCI-18), and immunogenicity. Volumetric MRI, plasma neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) were exploratory outcomes. The inclusion criterion for this post-hoc analysis was a baseline plasma p-tau217 level above the cutoff for AD.</p><p><strong>Results: </strong>Among 196 ADAMANT participants, 137 were positive for plasma p-tau217 (mean age 71.4 years, 59% women). AADvac1 was safe and well tolerated in this subgroup. AADvac1 reduced the rate of accumulation of log-plasma NfL by 56% and that of GFAP by 73%. The treatment differences in the CDR-SB and ADCS-ADL-MCI-18 scores favored AADvac1 but were not statistically significant. AADvac1 had no effect on whole-brain volume but nonsignificantly reduced the loss of brain cortical tissue in several regions. Importantly, the impact on the study outcomes was more pronounced in participants with higher anti-tau antibody levels.</p><p><strong>Conclusions: </strong>These results suggest that AADvac1 tau immunotherapy can reduce plasma biomarkers of neurodegeneration and neuroinflammation. These findings and possible observations on brain atrophy and cognition are hypothesis-generating and warrant further evaluation in a larger clinical trial.</p><p><strong>Trial registration: </strong>EudraCT 2015-000630-30 (primary) and NCT02579252.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"254"},"PeriodicalIF":7.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142694975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontotemporal structure preservation underlies the protective effect of lifetime intellectual cognitive reserve on cognition in the elderly.","authors":"Dandan Wang, Xin Li, Mingxi Dang, Shaokun Zhao, Feng Sang, Zhanjun Zhang","doi":"10.1186/s13195-024-01613-6","DOIUrl":"10.1186/s13195-024-01613-6","url":null,"abstract":"<p><strong>Background: </strong>Cognitive decline with age has heterogeneous, which might be related to the accumulation of protective factors called cognitive reserve, especially intellectual engagement factors over the life course. However, how lifetime intellectual cognitive reserve (LICR) protects cognitive function in the elderly remains unclear. We aimed to examine the relationship between LICR and cognition and the mild cognitive impairment (MCI) risk, as well as the neural mechanism of LICR on cognition.</p><p><strong>Methods: </strong>A total of 5126 participants completed extensive neuropsychological tests, with LICR indicator encompassing early education, midlife occupational complexity, and mental leisure activities after retirement. Confirmatory factor analysis was performed to derive LICR score and cognitive function scores, then the hierarchical regression analysis was used to explore the relationship between LICR and cognitive functions and the risk of MCI. We further explored the macro- and micro-structural preservation underly LICR in 1117 participants. Multiple regressions and tract-based spatial statistics were used to explore the relationship between LICR and gray matter volume and white matter microstructure (FA value). Finally, using the mediation model to explore the relationship of \"LICR-brain-cognition\".</p><p><strong>Result: </strong>The new LICR index, which was more protective than its single indexes, could protect widespread cognitive functions and was associated with a reduction in MCI risk (Odds Ratio, 0.52; 95% CI, 0.47-0.57). For the structure basis of LICR, the higher LICR score was associated with the greater gray matter volume in right fusiform gyrus (t = 4.62, FDR corrected, p < 0.05) and left orbital superior frontal gyrus (t = 4.56, FDR corrected, p < 0.05), and the higher FA values in the frontotemporal related white matter fiber tracts. Furthermore, the right fusiform gyrus partially mediated the relationship between LICR and executive processing ability (β = 0.01, p = 0.02) and general cognitive ability (β = 0.01, p = 0.03).</p><p><strong>Conclusions: </strong>The new comprehensive cognitive reserve index could promote the temporal macro-structural preservation and thus contribute to maintain better cognitive function. These findings highlight the importance of intellectual CR accumulation over the life course in successful cognitive aging and MCI prevention, thereby contributing to improve the quality of life in the elderly.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"255"},"PeriodicalIF":7.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated plasma p-tau231 is associated with reduced generalization and medial temporal lobe dynamic network flexibility among healthy older African Americans.","authors":"Miray Budak, Bernadette A Fausto, Zuzanna Osiecka, Mustafa Sheikh, Robert Perna, Nicholas Ashton, Kaj Blennow, Henrik Zetterberg, Patricia Fitzgerald-Bocarsly, Mark A Gluck","doi":"10.1186/s13195-024-01619-0","DOIUrl":"10.1186/s13195-024-01619-0","url":null,"abstract":"<p><strong>Background: </strong>Phosphorylated tau (p-tau) and amyloid beta (Aβ) in human plasma may provide an affordable and minimally invasive method to evaluate Alzheimer's disease (AD) pathophysiology. The medial temporal lobe (MTL) is susceptible to changes in structural integrity that are indicative of the disease progression. Among healthy adults, higher dynamic network flexibility within the MTL was shown to mediate better generalization of prior learning, a measure which has been demonstrated to predict cognitive decline and neural changes in preclinical AD longitudinally. Recent developments in cognitive, neural, and blood-based biomarkers of AD risk that may correspond with MTL changes. However, there is no comprehensive study on how these generalization biomarkers, long-term memory, MTL dynamic network flexibility, and plasma biomarkers are interrelated. This study investigated (1) the relationship between long-term memory, generalization performance, and MTL dynamic network flexibility and (2) how plasma p-tau231, p-tau181, and Aβ42/Aβ40 influence generalization, long-term memory, and MTL dynamics in cognitively unimpaired older African Americans.</p><p><strong>Methods: </strong>148 participants (Mean_age: 70.88,SD_age: 6.05) were drawn from the ongoing longitudinal study, Pathways to Healthy Aging in African Americans conducted at Rutgers University-Newark. Cognition was evaluated with the Rutgers Acquired Equivalence Task (generalization task) and Rey Auditory Learning Test (RAVLT) delayed recall. MTL dynamic network connectivity was measured from functional Magnetic Resonance Imaging data. Plasma p-tau231, p-tau181, and Aβ42/Aβ40 were measured from blood samples.</p><p><strong>Results: </strong>There was a significant positive correlation between generalization performance and MTL Dynamic Network Flexibility (t = 3.372, β = 0.280, p < 0.001). There were significant negative correlations between generalization performance and plasma p-tau231 (t = -3.324, β = -0.265, p = 0.001) and p-tau181 (t = -2.408, β = -0.192, p = 0.017). A significant negative correlation was found between plasma p-tau231 and MTL Dynamic Network Flexibility (t = -2.825, β = -0.232, p = 0.005).</p><p><strong>Conclusions: </strong>Increased levels of p-tau231 are associated with impaired generalization abilities and reduced dynamic network flexibility within the MTL. Plasma p-tau231 may serve as a potential biomarker for assessing cognitive decline and neural changes in cognitively unimpaired older African Americans.</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"253"},"PeriodicalIF":7.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A digitally supported multimodal lifestyle program to promote brain health among older adults (the LETHE randomized controlled feasibility trial): study design, progress, and first results.","authors":"Anna Rosenberg, Helena Untersteiner, Anna Giulia Guazzarini, Markus Bödenler, Jeroen Bruinsma, Bianca Buchgraber-Schnalzer, Matteo Colombo, Rik Crutzen, Ana Diaz, Dimitrios I Fotiadis, Hannes Hilberger, Simone Huber, Nico Kaartinen, Thomas Kassiotis, Miia Kivipelto, Jenni Lehtisalo, Vasileios S Loukas, Jyrki Lötjönen, Mattia Pirani, Charlotta Thunborg, Sten Hanke, Francesca Mangialasche, Patrizia Mecocci, Elisabeth Stögmann, Tiia Ngandu","doi":"10.1186/s13195-024-01615-4","DOIUrl":"10.1186/s13195-024-01615-4","url":null,"abstract":"<p><strong>Background: </strong>The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) multimodal lifestyle intervention yielded cognitive and other health benefits in older adults at risk of cognitive decline. The two-year multinational randomized controlled LETHE trial evaluates the feasibility of a digitally supported, adapted FINGER intervention among at-risk older adults. Technology is used to complement in-person activities, streamline the intervention delivery, personalize recommendations, and collect digital biomarkers.</p><p><strong>Methods: </strong>Trial includes older adults (60-77 years) with digital readiness/experience with smart devices and increased dementia risk but without substantial cognitive impairment. Participants are enrolled at four sites (Austria, Finland, Italy, Sweden). At baseline, participants were randomized 1:1 ratio to 1) intervention i.e., structured multimodal lifestyle program (including diet, exercise, cognitive training, vascular/metabolic risk management, social stimulation, sleep/stress management) where in-person activities led by professionals are supported with an Android mobile phone application developed by the consortium (the LETHE App); or 2) control i.e., self-guided program (regular health advice; simplified App with no personalized/interactive content). All participants wear smartwatches to gather passive data (e.g., physical activity, sleep). Primary outcomes are retention, adherence, and change in validated dementia risk scores. Secondary outcomes include changes in lifestyle, cognition, stress, sleep, health-related quality of life, and health literacy. Additional outcomes (exploratory) include e.g. participant experiences and dementia-related biomarkers (Alzheimer's disease blood markers, neuroimaging). A sub-study explores the feasibility of novel interactive technology (audio glasses, social robot).</p><p><strong>Results: </strong>Recruitment began in September 2022, and the last participant was randomized in June 2023. In total, 156 individuals were randomized (mean age 69 years, 65% women; balanced recruitment across the four sites). Vascular and lifestyle risk factors were common (e.g., 65% with hypertension, 69% with hypercholesterolemia, 39% physically inactive), indicating successful recruitment of a population with risk reduction potential. Trial will be completed by summer 2025. Retention until the first post-baseline visit at 6 months is high (n = 2 discontinued, retention 98.7%).</p><p><strong>Conclusion: </strong>LETHE provides crucial information about the feasibility of technology and a digitally supported FINGER lifestyle program to promote brain health. Digital tools specifically designed for older adults could offer potential for large-scale, cost-effective prevention programs.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT05565170).</p>","PeriodicalId":7516,"journal":{"name":"Alzheimer's Research & Therapy","volume":"16 1","pages":"252"},"PeriodicalIF":7.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}