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JOURNAL ARTICLE
Junfang Zhang, Haijuan Chen, Jie Wang, Qi Huang, Xiaomeng Xu, Wenjing Wang, Wei Xu, Yihui Guan, Jun Liu, Joanna M Wardlaw, Yulei Deng, Fang Xie, Binyin Li
INTRODUCTION: We investigated the association between white matter hyperintensities (WMH) and regional cortical thickness, amyloid and tau deposition, and synaptic density in the WMH-connected cortex using multimodal images. METHODS: We included 107 participants (59 with Alzheimer's disease [AD]; 27 with mild cognitive impairment; 21 cognitively normal controls) with amyloid beta (Aβ) positivity on amyloid positron emission tomography (PET). The cortex connected to WMH was identified using probabilistic tractography...
April 22, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Gazi Saadmaan, Maria Carolina Dalmasso, Alfredo Ramirez, Mikko Hiltunen, Nina Kemppainen, Jenni Lehtisalo, Francesca Mangialasche, Tiia Ngandu, Juha Rinne, Hilkka Soininen, Ruth Stephen, Miia Kivipelto, Alina Solomon
INTRODUCTION: We assessed a genetic risk score for Alzheimer's disease (AD-GRS) and apolipoprotein E (APOE4) in an exploratory neuroimaging substudy of the FINGER trial. METHODS: 1260 at-risk older individuals without dementia were randomized to multidomain lifestyle intervention or health advice. N = 126 participants underwent magnetic resonance imaging (MRI), and N = 47 positron emission tomography (PET) scans (Pittsburgh Compund B [PiB], Fluorodeoxyglucose) at baseline; N = 107 and N = 38 had repeated 2-year scans...
April 22, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Takashi Sakurai, Taiki Sugimoto, Hiroyasu Akatsu, Takehiko Doi, Yoshinori Fujiwara, Akihiro Hirakawa, Fumie Kinoshita, Masafumi Kuzuya, Sangyoon Lee, Nanae Matsumoto, Koichiro Matsuo, Makoto Michikawa, Akinori Nakamura, Susumu Ogawa, Rei Otsuka, Kenji Sato, Hiroyuki Shimada, Hiroko Suzuki, Hiroyuki Suzuki, Hajime Takechi, Shinya Takeda, Kazuaki Uchida, Hiroyuki Umegaki, Satomu Wakayama, Hidenori Arai
INTRODUCTION: We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI). METHODS: Participants aged 65-85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months. RESULTS: Of 531 participants, 406 completed the trial...
April 22, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Katheryn A Q Cousins, Jeffrey S Phillips, Sandhitsu R Das, Kyra O'Brien, Thomas F Tropea, Alice Chen-Plotkin, Leslie M Shaw, Ilya M Nasrallah, Dawn Mechanic-Hamilton, Corey T McMillan, David J Irwin, Edward B Lee, David A Wolk
INTRODUCTION: We investigate pathological correlates of plasma phosphorylated tau 181 (p-tau181 ), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) across a clinically diverse spectrum of neurodegenerative disease, including normal cognition (NormCog) and impaired cognition (ImpCog). METHODS: Participants were NormCog (n = 132) and ImpCog (n = 461), with confirmed β-amyloid (Aβ+/-) status (cerebrospinal fluid, positron emission tomography, autopsy) and single molecule array plasma measurements...
April 21, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Mateus Rozalem Aranha, Victor Montal, Hilde van den Brink, Jordi Pegueroles, Maria Carmona-Iragui, Laura Videla, Lucia Maure Blesa, Bessy Benejam, Javier Arranz, Sílvia Valldeneu, Isabel Barroeta, Susana Fernández, Laia Ribas, Daniel Alcolea, Sofía González-Ortiz, Núria Bargalló, Geert Jan Biessels, Rafael Blesa, Alberto Lleó, Artur Martins Coutinho, Cláudia Costa Leite, Alexandre Bejanin, Juan Fortea
BACKGROUND: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS...
April 21, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
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No abstract text is available yet for this article.
April 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Niccolo' Tesi, Sven van der Lee, Marc Hulsman, Natasja M van Schoor, Martijn Huisman, Yolande Pijnenburg, Wiesje M van der Flier, Marcel Reinders, Henne Holstege
BACKGROUND: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD. METHODS: Genome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians...
April 18, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Jie Wang, Qi Huang, Kun He, Junpeng Li, Tengfei Guo, Yang Yang, Zengping Lin, Songye Li, Greet Vanderlinden, Yiyun Huang, Koen Van Laere, Yihui Guan, Qihao Guo, Ruiqing Ni, Binying Li, Fang Xie
INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18 F]SynVesT-1 and [18 F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability...
April 18, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Robin B Brown, Daniel J Tozer, Laurence Loubière, Eric L Harshfield, Young T Hong, Tim D Fryer, Guy B Williams, Martin J Graves, Franklin I Aigbirhio, John T O'Brien, Hugh S Markus
INTRODUCTION: Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood-brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability. We determined whether minocycline had a similar effect in patients with SVD. METHODS: MINERVA was a single-center, phase II, randomized, double-blind, placebo-controlled trial...
April 17, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Lisa C Silbert, Natalie E Roese, Victoria Krajbich, Justin Hurworth, David Lahna, Daniel L Schwartz, Hiroko H Dodge, Randall L Woltjer
INTRODUCTION: Age-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes. METHODS: Brain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants who came to autopsy underwent post mortem (PM) 7 tesla MRI with targeted histopathological sampling of WMHs and NAWM...
April 17, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Doris Patricia Molina-Henry, Rema Raman, Andy Liu, Oliver Langford, Keith Johnson, Leona K Shum, Crystal M Glover, Shobha Dhadda, Michael Irizarry, Gustavo Jimenez-Maggiora, Joel B Braunstein, Kevin Yarasheski, Venky Venkatesh, Tim West, Philip B Verghese, Robert A Rissman, Paul Aisen, Joshua D Grill, Reisa A Sperling
INTRODUCTION: In trials of amyloid-lowering drugs for Alzheimer's disease (AD), differential eligibility may contribute to under-inclusion of racial and ethnic underrepresented groups. We examined plasma amyloid beta 42/40 and positron emission tomography (PET) amyloid eligibility for the ongoing AHEAD Study preclinical AD program (NCT04468659). METHODS: Univariate logistic regression models were used to examine group differences in plasma and PET amyloid screening eligibility...
April 17, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Chandrama Ahmed, Hendrik J Greve, Carla Garza-Lombo, Jamie A Malley, James A Johnson, Adrian L Oblak, Michelle L Block
INTRODUCTION: Ozone (O3 ) is an air pollutant associated with Alzheimer's disease (AD) risk. The lung-brain axis is implicated in O3 -associated glial and amyloid pathobiology; however, the role of disease-associated astrocytes (DAAs) in this process remains unknown. METHODS: The O3 -induced astrocyte phenotype was characterized in 5xFAD mice by spatial transcriptomics and proteomics. Hmgb1fl/fl LysM-Cre+ mice were used to assess the role of peripheral myeloid cell high mobility group box 1 (HMGB1)...
April 16, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Danielle C Lopez, Zachary J White, Stephanie E Hall
INTRODUCTION: Alzheimer's disease (AD) is characterized by cognitive impairments; however, heightened anxiety often accompanies and, in some cases, exacerbates cognitive its. The present study aims to understand the influence of multiple variables on anxiety-like behavior in TgF344-AD rats and determine whether anxiety impacts memory performance. METHODS: An elevated plus maze was used to assess anxiety-like behavior in the established colony (n = 107)...
April 16, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Maurice Pasternak, Saira S Mirza, Nicholas Luciw, Henri J M M Mutsaerts, Jan Petr, David Thomas, David Cash, Martina Bocchetta, Maria Carmela Tartaglia, Sara B Mitchell, Sandra E Black, Morris Freedman, David Tang-Wai, Ekaterina Rogaeva, Lucy L Russell, Arabella Bouzigues, John C van Swieten, Lize C Jiskoot, Harro Seelaar, Robert Laforce, Pietro Tiraboschi, Barbara Borroni, Daniela Galimberti, James B Rowe, Caroline Graff, Elizabeth Finger, Sandro Sorbi, Alexandre de Mendonça, Chris Butler, Alex Gerhard, Raquel Sanchez-Valle, Fermin Moreno, Matthis Synofzik, Rik Vandenberghe, Simon Ducharme, Johannes Levin, Markus Otto, Isabel Santana, Antonio P Strafella, Bradley J MacIntosh, Jonathan D Rohrer, Mario Masellis
INTRODUCTION: Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. METHODS: We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non-carrier controls...
April 16, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Jiang Chen, Zhi Zhang, Ying Liu, Lili Huang, Yi Liu, Dan Yang, Xinyu Bao, Pinyi Liu, Yuhan Ge, Qingqing Li, Xin Shu, Lushan Xu, Yun Stone Shi, Xiaolei Zhu, Yun Xu
INTRODUCTION: Cognitive decline progresses with age, and Nr4a1 has been shown to participate in memory functions. However, the relationship between age-related Nr4a1 reduction and cognitive decline is undefined. METHODS: Nr4a1 expressions were evaluated by quantitative PCR and immunochemical approaches. The cognition of mice was examined by multiple behavioral tests. Patch-clamp experiments were conducted to investigate the synaptic function. RESULTS: NR4A1 in peripheral blood mononuclear cells decreased with age in humans...
April 11, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Zarui A Melikyan, Claudia H Kawas, Annlia Paganini-Hill, Luohua Jiang, Syed Bukhari, Thomas J Montine, Bryce A Mander, María M Corrada
INTRODUCTION: We investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest-old (age 90+) participants of The 90+ Study. METHODS: Participants self-reported sleep duration and underwent neuropathologic evaluation. We categorized sleep duration as < 7, 7 to 8 = reference, > 8 hours and dichotomized neuropathologic changes as present/absent. We estimated odds ratio (OR) and 95% confidence intervals (CI) using logistic regression...
April 11, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#17
JOURNAL ARTICLE
Ronald L Simons, Mei Ling Ong, Man-Kit Lei, Steven R H Beach, Yue Zhang, Robert Philibert, Michelle M Mielke
INTRODUCTION: Recent evidence suggests that exposure to the stress of racism may increase the risk of dementia for Black Americans. METHODS: The present study used 17 years of data from a sample of 255 Black Americans to investigate the extent to which exposure to racial discrimination predicts subsequent changes in serum Alzheimer's Disease Research Center (ADRC) biomarkers: serum phosphorylated tau181(p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)...
April 10, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#18
JOURNAL ARTICLE
Andrew J Petkus, Xinhui Wang, Diana Younan, Lauren E Salminen, Susan M Resnick, Stephen R Rapp, Mark A Espeland, Margaret Gatz, Keith F Widaman, Ramon Casanova, Helena Chui, Ryan T Barnard, Sarah A Gaussoin, Joseph S Goveas, Kathleen M Hayden, Victor W Henderson, Bonnie C Sachs, Santiago Saldana, Aladdin H Shadyab, Sally A Shumaker, Jiu-Chiuan Chen
INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories...
April 9, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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JOURNAL ARTICLE
Shoichiro Sato, Naohisa Hatakeyama, Shinji Fujikoshi, Sadao Katayama, Hideaki Katagiri, John R Sims
INTRODUCTION: Donanemab, a monoclonal antibody directed against an insoluble, modified, N-terminal truncated form of amyloid beta, demonstrated efficacy and safety in patients with early, symptomatic Alzheimer's disease (AD) in the phase 3 TRAILBLAZER-ALZ 2 trial. Here, we report clinical outcomes, biomarkers, and safety results for the Japanese subpopulation. METHODS: TRAILBLAZER-ALZ 2 (N = 1736) was conducted in eight countries, including Japan (enrollment June 2020-November 2021; database lock April 2023)...
April 6, 2024: Neurology and Therapy
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JOURNAL ARTICLE
Michelle M Dunk, Stephen R Rapp, Kathleen M Hayden, Mark A Espeland, Ramon Casanova, JoAnn E Manson, Aladdin H Shadyab, Robert Wild, Ira Driscoll
INTRODUCTION: Apolipoprotein E4 (APOE4) carriers' tendency toward hypercholesterolemia may contribute to Alzheimer's disease (AD) risk through oxysterols, which traverse the blood-brain barrier. METHODS: Relationships between baseline plasma oxysterols, APOE status, serum lipids, and cognitive impairment risk were examined in 328 postmenopausal women from the Women's Health Initiative Memory Study. Women were followed for 25 years or until incident dementia or cognitive impairment...
April 4, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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