Article
Neuroimaging
Breton M. Asken, William G. Mantyh, Renaud La Joie, Amelia Strom, Kaitlin B. Casaletto, Adam M. Staffaroni, Alexandra C. Apple, Cutter A. Lindbergh, Leonardo Iaccarino, Michelle You, Harli Grant, Corrina Fonseca, Charles Windon, Kyan Younes, Jeremy Tanner, Gil D. Rabinovici, Joel H. Kramer, Raquel C. Gardner
Summary: In clinically normal older adults, a history of mTBI is not associated with higher cortical A beta burden and does not interact with A beta burden to affect cognition. However, remote mTBI may be linked to a faster rate of A beta accumulation.
BRAIN IMAGING AND BEHAVIOR
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jarith L. Ebenau, Denise Visser, Sander C. J. Verfaillie, Tessa Timmers, Mardou S. S. A. van Leeuwenstijn, Mara ten Kate, Albert D. Windhorst, Frederik Barkhof, Philip Scheltens, Niels D. Prins, Ronald Boellaard, Wiesje M. van der Flier, Bart N. M. van Berckel
Summary: This study investigated the associations between cerebral blood flow (CBF), amyloid burden, and cognition in cognitively normal individuals with subjective cognitive decline (SCD). The results suggest that amyloid accumulation and decrease in rCBF are two parallel disease processes without a fixed order, and both provide unique predictive information for cognitive decline, with each process enhancing the other longitudinally.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Clinical Neurology
Michelle E. Farrell, Kathryn Papp, Rachel F. Buckley, Heidi I. L. Jacobs, Aaron P. Schultz, Michael J. Properzi, Patrizia Vannini, Bernard J. Hanseeuw, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling
Summary: This study demonstrates that the emergence of AD pathology detected by PET is associated with declining processing speeds and memory retrieval in clinically normal older adults. These cognitive measures may be useful in determining the effectiveness of early interventions in preserving cognitive function.
Article
Neurosciences
Yong-Bo Zheng, Jie Sun, Le Shi, Si-Zhen Su, Xuan Chen, Qian-Wen Wang, Yue-Tong Huang, Yi-Jie Wang, Xi-Mei Zhu, Jian-Yu Que, Na Zeng, Xiao Lin, Kai Yuan, Wei Yan, Jia-Hui Deng, Jie Shi, Yan-Ping Bao, Lin Lu
Summary: This study found no significant association between caffeine consumption and brain amyloid positivity in older adults. However, caffeine consumption may be inversely associated with amyloid positivity among males. Further research is needed to explore the mechanisms underlying the relationship between caffeine consumption and brain amyloid positivity.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Geriatrics & Gerontology
Gillian Coughlan, Brennan DeSouza, Peter Zhukovsky, Michael Hornberger, Cheryl Grady, Rachel F. Buckley
Summary: This study investigated the association between cerebrospinal fluid biomarkers (p-tau and β-amyloid) and spatial cognition in clinically normal older adults. The results showed significant correlations between these biomarkers and spatial cognition scores on two tasks. Lower entorhinal cortical volume was associated with poorer performance on both tasks and accounted for 18%-22% of the direct association between p-tau and spatial cognition scores. The degeneration of the entorhinal cortex plays a significant mediating role in the association between p-tau and spatial assessments in cognitively normal adults.
NEUROBIOLOGY OF AGING
(2023)
Article
Psychiatry
Pratishtha Chatterjee, Steve Pedrini, Erik Stoops, Kathryn Goozee, Victor L. Villemagne, Prita R. Asih, Inge M. W. Verberk, Preeti Dave, Kevin Taddei, Hamid R. Sohrabi, Henrik Zetterberg, Kaj Blennow, Charlotte E. Teunissen, Hugo M. Vanderstichele, Ralph N. Martins
Summary: The study found that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD, indicating that astrocytic damage or activation may start from the pre-symptomatic stage of the disease and is associated with brain Aβ load. The potential of plasma GFAP to contribute to a diagnostic blood biomarker panel, along with plasma Aβ 1-42/Aβ 1-40 ratios, for cognitively normal older adults at risk of AD was highlighted by the observations from the present study.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Clinical Neurology
Laura M. Van der Kall, Thanh Truong, Samantha C. Burnham, Vincent Dore, Rachel S. Mulligan, Svetlana Bozinovski, Fiona Lamb, Pierrick Bourgeat, Jurgen Fripp, Stephanie Schultz, Yen Y. Lim, Simon M. Laws, David Ames, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Olivier Salvado, Joanne Robertson, Paul Maruff, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe
Summary: The study found that in cognitively normal older individuals, the level of beta-amyloid is related to the risk of progression to mild cognitive impairment or dementia. Higher levels of beta-amyloid were associated with increased risk of developing cognitive decline, indicating a potential biomarker for dementia risk assessment and preclinical AD trial design.
Article
Geriatrics & Gerontology
Steve Pedrini, Pratishtha Chatterjee, Akinori Nakamura, Michelle Tegg, Eugene Hone, Stephanie R. Rainey-Smith, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Naoki Kaneko, Sam L. Gardener, Kevin Taddei, Binosha Fernando, Ian Martins, Prashant Bharadwaj, Hamid R. Sohrabi, Colin L. Masters, Belinda Brown, Ralph N. Martins
Summary: This study aimed to evaluate the relationship between habitual physical activity levels and brain amyloid deposition and AD-related blood biomarkers. The results showed that higher levels of physical activity were associated with lower brain amyloid deposition and plasma protein levels. There were also differences in the blood biomarker ratios between APOE ε4 carriers and non-carriers.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Clinical Neurology
Rowan Saloner, Emily W. Paolillo, Kevin J. Wojta, Corrina Fonseca, Eva Q. Gontrum, Argentina Lario-Lago, Gil D. Rabinovici, Jennifer S. Yokoyama, Jessica E. Rexach, Joel H. Kramer, Kaitlin B. Casaletto
Summary: This study examined the sex-dependent associations of variation in the SNAP-25 gene with cognitive and neuroimaging outcomes in Alzheimer's disease. The results showed that female C-allele carriers had better verbal memory, lower A beta-PET positivity rates, and larger temporal volumes compared to T/T homozygotes. The findings suggest that genetic variation in SNAP-25 may influence female-specific resistance to Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(2023)
Article
Multidisciplinary Sciences
Prokopis C. Prokopiou, Nina Engels-Dominguez, Kathryn Papp, Matthew R. Scott, Aaron P. Schultz, Christoph Schneider, Michelle E. Farrell, Rachel F. Buckley, Yakeel T. Quiroz, Georges El Fakhri, Dorene M. Rentz, Reisa A. Sperling, Keith A. Johnson, Heidi I. L. Jacobs
Summary: Cortical Alzheimer's Disease neuropathology is associated with cognitive decline, and the functional properties of the locus coeruleus (LC) can be used to identify individuals at risk for the disease.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Emma L. Twait, Britt Min, Magdalena Beran, Jet M. J. Vonk, Mirjam I. Geerlings
Summary: This systematic review and meta-analysis investigated the relationship between amyloid burden and white matter hyperintensities (WMH) in older adults without cognitive impairment. The findings revealed an association between amyloid pathology and WMH in cerebrospinal fluid (CSF) and positron emission tomography (PET), but the relationship in plasma remains unclear. Further studies should explore the relationship between plasma amyloid-beta and WMH to identify at-risk individuals in preclinical stages.
AGEING RESEARCH REVIEWS
(2023)
Article
Medicine, General & Internal
Andrea Sturchio, Alok K. Dwivedi, Christina B. Young, Tarja Malm, Luca Marsili, Jennifer S. Sharma, Abhimanyu Mahajan, Emily J. Hill, Samir El Andaloussi, Kathleen L. Poston, Fredric P. Manfredsson, Lon S. Schneider, Kariem Ezzat, Alberto J. Espay
Summary: The study found that high soluble Aβ42 levels are associated with normal cognition and hippocampal volume despite increasing brain amyloidosis, suggesting that preserving high soluble Aβ42 levels could be important for maintaining cognitive function and hippocampal health.
Article
Neurosciences
Jinghang Li, Elizabeth J. Mountz, Akiko Mizuno, Ashti M. Shah, Andrea Weinstein, Ann D. Cohen, William E. Klunk, Beth E. Snitz, Howard J. Aizenstein, Helmet T. Karim
Summary: This study found that genetic risk of Alzheimer's disease (AD) and markers of AD are associated with neural asymmetry during working memory and executive function processing. Individuals with higher genetic risk of AD showed lower asymmetry in angular gyrus activation, while individuals with higher education showed lower asymmetry in mediodorsal thalamus activation.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Geriatrics & Gerontology
Lok-Kin Yeung, Christiane Hale, Batool Rizvi, Kay Igwe, Richard P. Sloan, Lawrence S. Honig, Scott A. Small, Adam M. Brickman
Summary: The study found that the volume of the anterolateral entorhinal cortex (alERC) is associated with verbal memory retention and certain aspects of neuropsychological test performance, potentially related to cognitive impairments in Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2021)
Article
Geriatrics & Gerontology
Wei Xu, Chen-Chen Tan, Xi-Peng Cao, Lan Tan
Summary: The study found that PGRN and neuroinflammatory markers increased over the course of Alzheimer's disease, and neuroinflammation can modulate the association of PGRN with amyloid pathologies. Neuroinflammatory markers significantly modulated the relationship between amyloid burden and CSF PGRN, which could predict cognitive decline and lower AD risk in certain groups.
NEUROBIOLOGY OF AGING
(2021)
Review
Clinical Neurology
Harald Hampel, Leslie M. Shaw, Paul Aisen, Christopher Chen, Alberto Lleo, Takeshi Iwatsubo, Atsushi Iwata, Masahito Yamada, Takeshi Ikeuchi, Jianping Jia, Huali Wang, Charlotte E. Teunissen, Elaine Peskind, Kaj Blennow, Jeffrey Cummings, Andrea Vergallo
Summary: The article discusses the necessity and inconsistency of lumbar puncture in the diagnosis of Alzheimer's disease, highlighting the importance of lumbar puncture in early diagnosis and treatment.
ALZHEIMERS & DEMENTIA
(2022)
Article
Cardiac & Cardiovascular Systems
Kenichiro Sato, Atsushi Iwata, Masanori Kurihara, Tatsuo Mano, Tatsushi Toda
Summary: The study found significantly higher reporting odds ratios (ROR) for stress cardiomyopathy (TTS) following the use of certain adrenergic drugs, predominantly in women and patients in their 70s. The results suggest a potential association of taking midodrine or droxidopa with the development of TTS.
JOURNAL OF CARDIOLOGY
(2022)
Article
Clinical Neurology
K. V. Papp, H. Rofael, A. E. Veroff, M. C. Donohue, S. Wang, C. Randolph, E. Grober, H. R. Brashear, G. Novak, K. Ernstrom, R. Raman, P. S. Aisen, R. Sperling, G. Romano, D. Henley
Summary: Cognitive composites are commonly used in Alzheimer's disease secondary prevention trials. This study found that individuals with A beta+ status performed worse on cognitive composites, but the effect size was generally small. Memory tests and speed of processing exhibited the largest A beta+/- effect sizes.
JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Michael S. Rafii, Reisa A. Sperling, Michael C. Donohue, Jin Zhou, Claire Roberts, Michael C. Irizarry, Shobha Dhadda, Gopalan Sethuraman, Lynn D. Kramer, Chad J. Swanson, David Li, Stephen Krause, Robert A. Rissman, Sarah Walter, Rema Raman, Keith A. Johnson, Paul S. Aisen
Summary: The AHEAD 3-45 Study aims to investigate the feasibility of intervention therapy before the clinical symptoms of Alzheimer's disease appear, and utilizes innovative approaches to accelerate the screening process for selecting suitable participants.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Philip S. Insel, Christina B. Young, Paul S. Aisen, Keith A. Johnson, Reisa A. Sperling, Elizabeth C. Mormino, Michael C. Donohue
Summary: The rates of tau accumulation in cognitively unimpaired older adults are subtle and vary in magnitude and spatial patterns. The degree of regional accumulation also likely depends on the amyloid-beta-dependent accumulation. Therefore, it is important to evaluate the pattern and consistency of tau accumulation across multiple cohorts and its relationship with amyloid burden to design optimal tau endpoints for clinical trials.
Article
Clinical Neurology
Harald Hampel, Aya Elhage, Leslie M. Shaw, Paul Aisen, Christopher Chen, Alberto Lleo, Takeshi Iwatsubo, Atsushi Iwata, Masahito Yamada, Takeshi Ikeuchi, Jianping Jia, Huali Wang, Charlotte E. Teunissen, Elaine Peskind, Kaj Blennow, Jeffrey Cummings, Andrea Vergallo
Summary: This article is a summary of the safe use of lumbar puncture in diagnosing Alzheimer's disease and other forms of dementia. Despite the low risk of complications, there may be reluctance among physicians and patients to recommend or undergo this procedure. Patient education, specialist training, and new methods for patient safety are important factors in supporting the widespread use of lumbar puncture in Alzheimer's disease.
NEURODEGENERATIVE DISEASE MANAGEMENT
(2022)
Article
Clinical Neurology
Roos J. Jutten, Kathryn Papp, Suzanne Hendrix, Noel Ellison, Jessica B. Langbaum, Michael C. Donohue, Jason Hassenstab, Paul Maruff, Dorene M. Rentz, John Harrison, Jeffrey Cummings, Philip Scheltens, Sietske A. M. Sikkes
Summary: Using the right outcome measure is crucial in clinical trials. However, there has been relatively less progress in the evolution of clinical outcome assessments (COAs) for the early stages of Alzheimer's disease (AD). This paper aims to provide guidance for the design and evaluation of COAs for use in early AD trials and proposes a framework for assessing clinically meaningful changes. Recommendations are also given to facilitate the implementation of more effective cognitive outcome measures in AD trials.
ALZHEIMERS & DEMENTIA
(2023)
Letter
Geriatrics & Gerontology
Keiko Hatano, Yasushi Nishina, Kazutomi Kanemaru, Atsushi Iwata
GERIATRICS & GERONTOLOGY INTERNATIONAL
(2022)
Article
Clinical Neurology
Monica Rivera Mindt, Ozioma Okonkwo, Michael W. Weiner, Dallas P. Veitch, Paul Aisen, Miriam Ashford, Godfrey Coker, Michael C. Donohue, Kenneth M. Langa, Garrett Miller, Ronald Petersen, Rema Raman, Rachel Nosheny
Summary: The poor generalizability of clinical research data due to the enrollment of highly educated, non-Latinx White participants hampers the development of therapies for Alzheimer's disease (AD). Black and Latinx older adults have a greater risk for dementia, yet it is unclear how health-care disparities and sociocultural factors influence potential AD therapies and prognosis. Low enrollment of under-represented populations may be attributable to several factors including greater exclusion due to higher rates of comorbidities, lower access to AD clinics, and the legacy of unethical treatment in medical research. This perspective outlines solutions tested in the Brain Health Registry (BHR) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), including culturally-informed digital research methods, community-engaged research strategies, leadership from under-represented communities, and the reduction of exclusion criteria based on comorbidities. Our successes demonstrate that it is possible to increase the inclusion and engagement of under-represented populations into US-based clinical studies, thereby increasing the generalizability of their results.
ALZHEIMERS & DEMENTIA
(2023)
Article
Pharmacology & Pharmacy
Michael C. Donohue, Oliver Langford, Philip S. Insel, Christopher H. van Dyck, Ronald C. Petersen, Suzanne Craft, Gopalan Sethuraman, Rema Raman, Paul S. Aisen
Summary: Mixed model repeated measures (MMRM) is commonly used in clinical trials for analyzing continuous outcomes over time. However, categorizing time as a categorical variable can lead to bias and exclusion of valuable information. In this study, a constrained longitudinal data analysis with natural cubic splines is proposed as an alternative to MMRM, showing better precision and power in clinical trial datasets and simulation scenarios.
PHARMACEUTICAL STATISTICS
(2023)
Article
Cell Biology
Harald Hampel, Rhoda Au, Soeren Mattke, Wiesje M. M. van der Flier, Paul Aisen, Liana Apostolova, Christopher Chen, Min Cho, Susan De Santi, Peng Gao, Atsushi Iwata, Ricky Kurzman, Andrew J. J. Saykin, Stefan Teipel, Bruno Vellas, Andrea Vergallo, Huali Wang, Jeffrey Cummings
Summary: This Perspective discusses the reconceptualization of Alzheimer's disease as a clinical and biological construct and proposes a new framework for clinical care pathways that incorporates biomarker-guided and digitally facilitated decision-making algorithms. The challenges and potential solutions for this transformation are addressed.
Article
Clinical Neurology
Kensaku Kasuga, Masataka Kikuchi, Tamao Tsukie, Kazushi Suzuki, Ryoko Ihara, Atsushi Iwata, Norikazu Hara, Akinori Miyashita, Ryozo Kuwano, Takeshi Iwatsubo, Takeshi Ikeuchi
Summary: The AT(N) classification aids in understanding the significance of Alzheimer's disease continuum biology in various populations, as it can categorize individuals based on different biomarkers.
BMJ NEUROLOGY OPEN
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Kenji Ishibashi, Yoshiharu Miura, Tetsuro Tago, Jun Toyohara, Mana Higashihara, Atsushi Iwata, Kenji Ishii
Summary: This study examined the distribution pattern of F-18-THK5351 in the healthy brain and found that its uptake largely reflects the concentrations of MAO-B under normal conditions.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Cell Biology
Takayuki Kondo, Norikazu Hara, Satoshi Koyama, Yuichiro Yada, Kayoko Tsukita, Ayako Nagahashi, Takeshi Ikeuchi, Kenji Ishii, Takashi Asada, Tetsuaki Arai, Ryo Yamada, Haruhisa Inoue
Summary: This study identified 24 significant genome-wide loci associated with alterations in amyloid beta production in Alzheimer's disease through a cellular dissection of polygenicity approach. The findings improve the predictions of amyloid positivity in the brains and cerebrospinal fluid of patients with Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Naoki Watanabe, Masaki Nakano, Yachiyo Mitsuishi, Norikazu Hara, Tatsuo Mano, Atsushi Iwata, Shigeo Murayama, Toshiharu Suzuki, Takeshi Ikeuchi, Masaki Nishimura
Summary: The study revealed that the downregulation of FAM3C in the AD brain may be a risk factor for A beta accumulation and eventually AD development. Transcriptional mechanisms involving SP1, EBF1, SMAD1, and KLF6 were identified as factors influencing the expression of FAM3C, with reduced nuclear levels of SP1 and EBF1 in AD brains contributing to the observed transcriptional downregulation.
HUMAN MOLECULAR GENETICS
(2022)