Review
Geriatrics & Gerontology
Syuichi Tetsuka
Summary: Depression and dementia are common neuropsychiatric disorders in older adults, with distinct differences in their presentation, diagnosis, and treatment approaches. It is crucial to differentiate between the two in clinical practice to provide appropriate care. Early recognition of common symptoms and prompt diagnosis of depression in dementia patients are essential for effective treatment.
Article
Biochemistry & Molecular Biology
Pratishtha Chatterjee, Yeo-Jin Cheong, Atul Bhatnagar, Kathryn Goozee, Yunqi Wu, Matthew McKay, Ian J. Martins, Wei L. F. Lim, Steve Pedrini, Michelle Tegg, Victor L. Villemagne, Prita R. Asih, Preeti Dave, Tejal M. Shah, Cintia B. Dias, Stephanie J. Fuller, Heidi Hillebrandt, Sunil Gupta, Eugene Hone, Kevin Taddei, Henrik Zetterberg, Kaj Blennow, Hamid R. Sohrabi, Ralph N. Martins
Summary: The study identified associations between plasma neurofilament light chain, a marker of neurodegeneration, and plasma metabolites, suggesting a link between neurodegeneration and biological pathways associated with Alzheimer's disease pathology. Further validation in independent cohorts is needed to explore the potential of these metabolites as prognostic markers for neurodegenerative diseases.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Clinical Neurology
Yi-Ming Huang, Ya-Hui Ma, Pei-Yang Gao, Zhi-Bo Wang, Liang-Yu Huang, Jia-Hui Hou, Lan Tan, Jin-Tai Yu
Summary: This study analyzed the link between plasma B2M and CSF AD biomarkers as well as cognition. The results showed that B2M levels were associated with cognitive impairment and changes in AD biomarkers. This suggests that B2M could be a potential biomarker for preclinical AD.
ALZHEIMERS RESEARCH & THERAPY
(2023)
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
Geriatrics & Gerontology
Zhichao Hao, Nicole Ruggiano, Qingyi Li, Yuqi Guo, Xiaofu Pan
Summary: Urban elderly NDs patients are more likely to suffer from depression, while elderly NDs patients who live with family members, self-assess their health as fair, or believe their health status remains the same are less likely to have depression.
AGING & MENTAL HEALTH
(2022)
Review
Psychology, Clinical
Harry Costello, Jonathan P. Roiser, Robert Howard
Summary: Depression in dementia is common and has negative effects on patients and carers. Antidepressants are widely used but lack evidence of efficacy, and may be harmful. More research is needed to understand why antidepressants are ineffective in dementia and to find new treatment targets. Clinicians continue to prescribe antidepressants, but novel approaches are needed to identify effective treatments for depression in dementia.
PSYCHOLOGICAL MEDICINE
(2023)
Review
Geriatrics & Gerontology
Erica Ercolano, Leonardo Bencivenga, Maria Emiliana Palaia, Giovanni Carbone, Francesco Scognamiglio, Giuseppe Rengo, Grazia Daniela Femminella
Summary: There is substantial evidence supporting a direct correlation between cognitive impairment, Alzheimer's disease, and sleep disorders, particularly obstructive sleep apnea. Obstructive sleep apnea may be considered a modifiable risk factor for cognitive dysfunction. Recent research focuses on examining the relationship and underlying mechanisms between obstructive sleep apnea and Alzheimer's disease biomarkers, as well as evaluating the potential benefits of obstructive sleep apnea therapy on cognitive function.
Article
Neurosciences
Ya-Hui Ma, Ya-Yu Wang, Lan Tan, Wei Xu, Xue-Ning Shen, Hui-Fu Wang, Xiao-He Hou, Xi-Peng Cao, Yan-Lin Bi, Qiang Dong, Jiu-Long Yang, Jin-Tai Yu
Summary: The study found that social networks were closely associated with multiple AD pathological indicators, especially in high-risk populations, suggesting that social networks may have an impact on the metabolism of multiple AD pathologies.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Neurosciences
Wen-Jie Cai, Yan Tian, Ya-Hui Ma, Qiang Dong, Lan Tan, Jin-Tai Yu
Summary: Anxiety is associated with amyloid-beta deposition and neurodegeneration in non-dementia elderly, while anxiety in MCI patients predicts conversion to dementia. Anxiety may have a selective role in predicting disease progression in the early phase of AD.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Geriatrics & Gerontology
Brendan L. McNeish, Iva Miljkovic, Xiaonan Zhu, Peggy M. Cawthon, Anne B. Newman, Bret Goodpaster, Kristine Yaffe, Caterina Rosano
Summary: This study found a positive association between serum myostatin levels and the amyloid burden in Alzheimer's disease. The association was significant in white men and women, but not in black men or women. Further investigation is needed to understand the role of myostatin in AD pathogenesis and its influence on different racial groups.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Geriatrics & Gerontology
Jessica M. Collins, Edward Hill, Aidan Bindoff, Anna E. King, Jane Alty, Mathew J. Summers, James C. Vickers
Summary: This study found that both early and mid-life education significantly influenced serum BDNF levels. Serum BDNF levels decreased with age, were lower in males compared to females, and the impact of the BDNF Val66Met genotype was small and non-significant.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Geriatrics & Gerontology
Sumika M. Lin, Marcus K. Borges, Alaise S. S. de Siqueira, Marina M. Biella, Wilson Jacob-Filho, Matteo Cesari, Richard C. Oude Voshaar, Ivan Aprahamian
Summary: The study found that the use of SSRI, depression, or frailty among older adults is associated with an increased risk of falls. SSRI usage is independently linked to falls, particularly in frail-depressed patients, alternative depression treatment strategies other than SSRIs should be considered.
AGING & MENTAL HEALTH
(2021)
Article
Geriatrics & Gerontology
Ginny Natale, Sean A. P. Clouston, Dylan M. Smith
Summary: This study examined the association between major stroke, probable Alzheimer's disease (AD), mixed AD, and C-reactive protein (CRP) levels in older adults, with and without depression. The findings revealed that participants with mixed AD had higher CRP levels compared to unimpaired participants, and those with mixed AD without depression had even higher CRP levels. Additionally, depressed adults with major stroke had lower CRP levels. These results suggest a potential link between inflammation and AD and the impact of depression on CRP levels.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Neurosciences
Lin-Lin Li, Ya-Hui Ma, Yan-Lin Bi, Fu-Rong Sun, Hao Hu, Xiao-He Hou, Wei Xu, Xue-Ning Shen, Qiang Dong, Lan Tan, Jiu-Long Yang, Jin-Tai Yu
Summary: The study found that elevated serum uric acid levels were associated with increased brain amyloid deposition in preclinical Alzheimer's disease, indicating a potential detrimental role of uric acid in AD pathology. Additionally, individuals with amyloid pathology had higher concentrations of uric acid, suggesting a possible link between uric acid levels and AD progression.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Chengjie Xiong, Jingqin Luo, Suzanne E. Schindler, Anne M. Fagan, Tammie Benzinger, Jason Hassenstab, Joyce E. Balls-Berry, Folasade Agboola, Elizabeth Grant, Krista L. Moulder, John C. Morris
Summary: This study found racial differences in the longitudinal changes of Alzheimer's disease biomarkers, with slower deposition of amyloid and different patterns of change in cerebrospinal fluid amyloid beta (Aβ)42 between Blacks and Whites. Additionally, the increase in cerebrospinal fluid total tau and phosphorylated tau181 was lower in Blacks compared to Whites.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Jonathan Voeglein, Nicolai Franzmeier, John C. Morris, Marianne Dieterich, Eric McDade, Mikael Simons, Oliver Preische, Anna Hofmann, Jason Hassenstab, Tammie L. Benzinger, Anne Fagan, James M. Noble, Sarah B. Berman, Neill R. Graff-Radford, Bernardino Ghetti, Martin R. Farlow, Jasmeer P. Chhatwal, Stephen Salloway, Chengjie Xiong, Celeste M. Karch, Nigel Cairns, Richard J. Perrin, Gregory Day, Ralph Martins, Raquel Sanchez-Valle, Hiroshi Mori, Hiroyuki Shimada, Takeshi Ikeuchi, Kazushi Suzuki, Peter R. Schofield, Colin L. Masters, Alison Goate, Virginia Buckles, Nick C. Fox, Patricio Chrem, Ricardo Allegri, John M. Ringman, Igor Yakushev, Christoph Laske, Mathias Jucker, Gunter Hoglinger, Randall J. Bateman, Adrian Danek, Johannes Levin
Summary: Autosomal dominant Alzheimer's disease (ADAD) has distinct neurological examination findings that are useful for estimating prognosis and guiding clinical care and therapeutic trial designs.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Patrick H. Luckett, Charlie Chen, Brian A. Gordon, Julie Wisch, Sarah B. Berman, Jasmeer P. Chhatwal, Carlos Cruchaga, Anne M. Fagan, Martin R. Farlow, Nick C. Fox, Mathias Jucker, Johannes Levin, Colin L. Masters, Hiroshi Mori, James M. Noble, Stephen Salloway, Peter R. Schofield, Adam M. Brickman, William S. Brooks, David M. Cash, Michael J. Fulham, Bernardino Ghetti, Clifford R. Jack, Jonathan Voeglein, William E. Klunk, Robert Koeppe, Yi Su, Michael Weiner, Qing Wang, Daniel Marcus, Deborah Koudelis, Nelly Joseph-Mathurin, Lisa Cash, Russ Hornbeck, Chengjie Xiong, Richard J. Perrin, Celeste M. Karch, Jason Hassenstab, Eric McDade, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances
Summary: This study analyzed 19 biomarkers of Alzheimer's disease using hierarchical clustering and feature selection, and found that amyloid and tau measures were the primary predictors. Emerging biomarkers of neuronal integrity and inflammation showed weaker predictive ability.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Sarah M. Hartz, Jessica Mozersky, Suzanne E. Schindler, Erin Linnenbringer, Junwei Wang, Brian A. Gordon, Cyrus A. Raji, Krista L. Moulder, Tim West, Tammie L. S. Benzinger, Carlos Cruchaga, Jason J. Hassenstab, Laura J. Bierut, Chengjie Xiong, John C. Morris
Summary: In this study, the authors developed and validated an adaptive tool to compute the absolute risks of Alzheimer's disease (AD) dementia, using demographic factors, clinical and cognitive variables, and biomarkers. This approach provides improved accuracy and communication of AD risk among cognitively unimpaired older adults.
ALZHEIMERS & DEMENTIA
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Anne M. Smith, Nancy A. Obuchowski, Norman L. Foster, Gregory Klein, P. David Mozley, Adriaan A. Lammertsma, Richard L. Wahl, John J. Sunderland, Jean-Luc Vanderheyden, Tammie L. S. Benzinger, Paul E. Kinahan, Dean F. Wong, Eric S. Perlman, Satoshi Minoshima, Dawn Matthews
Summary: Standardized approach in acquiring amyloid PET images increases their value as disease and drug response biomarkers. The Quantitative Imaging Biomarkers Alliance amyloid PET biomarker committee developed and validated a profile to characterize and reduce the variability of SUVRs, increasing statistical power for these assessments.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Clinical Neurology
Jessica Nicosia, Andrew J. Aschenbrenner, David A. Balota, Martin J. Sliwinski, Marisol Tahan, Sarah Adams, Sarah S. Stout, Hannah Wilks, Brian A. Gordon, Tammie L. S. Benzinger, Anne M. Fagan, Chengjie Xiong, Randall J. Bateman, John C. Morris, Jason Hassenstab
Summary: This study confirms the reliability and validity of the ARC smartphone application as a feasible tool for assessing cognitive changes associated with early stages of Alzheimer's disease in older adults. The ARC tasks are reliable and correlated with conventional cognitive measures and AD biomarker burden. The intensive 7-day cycle of ARC testing was feasible and well tolerated by older adult participants, receiving favorable ratings.
JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
(2023)
Article
Clinical Neurology
Pratishtha Chatterjee, Lisa Vermunt, Brian A. Gordon, Steve Pedrini, Lynn Boonkamp, Nicola J. Armstrong, Chengjie Xiong, Abhay K. Singh, Yan Li, Hamid R. Sohrabi, Kevin Taddei, Mark Molloy, Tammie L. S. Benzinger, John C. Morris, Celeste Karch, Sarah Berman, Jasmeer Chhatwal, Carlos Cruchaga, Neill R. Graff-Radford, Gregory S. Day, Martin Farlow, Nick Fox, Alison Goate, Jason Hassenstab, Jae-Hong Lee, Johannes Levin, Eric McDade, Hiroshi Mori, Richard Perrin, Raquel Sanchez-Valle, Peter R. Schofield, Allan Levey, Mathias Jucker, Colin L. Masters, Anne M. Fagan, Randall J. Bateman, Ralph N. Martins, Charlotte Teunissen
Summary: This study found that plasma GFAP levels increase a decade before symptom onset in AD and are associated with Aβ load, neurodegeneration, and cognitive decline.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Chengjie Xiong, Lena M. McCue, Virginia Buckles, Elizabeth Grant, Folasade Agboola, Dean Coble, Randall J. Bateman, Anne M. Fagan, Tammie L. S. Benzinger, Jason Hassenstab, Suzanne E. Schindler, Eric McDade, Krista Moulder, Brian A. Gordon, Carlos Cruchaga, Gregory S. Day, Takeshi Ikeuchi, Kazushi Suzuki, Ricardo F. Allegri, Jonathan Voeglein, Johannes Levin, John C. Morris
Summary: This study compared biomarkers of late-onset Alzheimer's disease (LOAD) and autosomal dominant AD (ADAD). The results showed that at baseline, ADAD mutation carriers (MCs) had lower CSF A beta 42 levels and higher levels of total and phosphorylated tau-181, and PiB uptake compared to LOAD participants with a positive family history (FH+). Longitudinally, MCs had a similar increase in PiB uptake to FH+, but a much faster decline in hippocampal volume, and were the only group showing cognitive decline.
ALZHEIMERS & DEMENTIA
(2023)
Letter
Clinical Neurology
P. M. Cogswell, C. R. Jack Jr, J. A. Barakos, F. Barkhof, T. S. Benzinger, C. A. Raji, T. Y. Poussaint, V. K. Ramanan, C. T. Whitlow
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Article
Clinical Neurology
F. Rahmani, S. Jindal, C. A. Raji, W. Wang, A. Nazeri, G. G. Perez-Carrillo, M. M. Miller-Thomas, P. Graner, B. Marechal, A. Shah, M. Zimmermann, C. D. Chen, S. Keefe, P. LaMontagne, T. L. S. Benzinger
Summary: Auto volumetric analysis of brain MRI provides quantitative assessment of brain atrophy. In this study, the performance of AI-Rad Companion brain MRI software was compared to FreeSurfer pipeline. The results showed strong correlation, moderate consistency, and poor agreement in volume measurements between the two tools. The AI-Rad Companion tool had high specificity and sensitivity in detecting volumetric abnormalities compared to the FreeSurfer pipeline. There was no difference in the compatibility of radiologic and clinical impressions between the two tools.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Article
Clinical Neurology
Kanta Horie, Yan R. Li, Nicolas Barthelemy, Brian Gordon, Jason Hassenstab, Tammie L. S. M. Benzinger, Anne C. Fagan, John M. Morris, Celeste Karch, Chengjie Xiong, Ricardo Allegri, Patricio Chrem Mendez, Takeshi Ikeuchi, Kensaku Kasuga, James Noble, Martin Farlow, Jasmeer Chhatwal, Gregory R. Day, Peter R. Schofield, Colin Masters, Johannes Levin, Mathias Jucker, Jae-Hong Lee, Jee Hoon Roh, Chihiro Sato, Pallavi Sachdev, Akihiko Koyama, Larisa J. Reyderman, Randall Bateman, Eric McDade
Summary: Identifying cerebrospinal fluid measures of the microtubule binding region of tau (MTBR-tau) species that reflect tau aggregation could provide fluid biomarkers that track Alzheimer's disease related neurofibrillary tau pathological changes.
ANNALS OF NEUROLOGY
(2023)
Article
Chemistry, Medicinal
Lin Qiu, Hao Jiang, Charles Zhou, Jinzhi Wang, Yanbo Yu, Haiyang Zhao, Tianyu Huang, Robert Gropler, Joel S. Perlmutter, Tammie L. S. Benzinger, Zhude Tu
Summary: S1PR1 receptor is a potential therapeutic and diagnostic target in neurological disorders, and researchers have designed, synthesized and evaluated novel F-18 S1PR1 radioligands. Compound 6h, with high potency and selectivity for S1PR1, showed promising results in imaging S1PR1 in the brain through positron emission tomography (PET) studies. Overall, [F-18]6h is a promising radioligand for S1PR1 imaging and worth further investigation in translational clinical studies for brain disorders in humans.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Clinical Neurology
Ganesh M. Babulal, Ling Chen, David B. Carr, Ann M. Johnson, Joshua S. Shimony, Jason Doherty, Samantha Murphy, Alexis Walker, Hailee Domash, Russ Hornbeck, Sarah Keefe, Shaney Flores, Cyrus A. Raji, John C. Morris, Beau M. Ances, Tammie L. S. Benzinger
Summary: This study found that older drivers with mild or moderate cortical atrophy and aging-related changes experienced a decrease in the number of monthly trips, particularly within a one-to-five-mile range from their residence, over a two-and-a-half-year period. Drivers with cerebral small vessel disease (CSVD) showed a larger reduction in daily driving behaviors compared to those without CSVD, indicating it as an early neurobehavioral marker for functional decline. The findings suggest that magnetic resonance imaging can be used to identify high-risk elderly drivers to ensure driving safety and community mobility.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Matthew R. Brier, Zhuocheng Li, Maria Ly, Helmet T. Karim, Leda Liang, Weixin Du, John E. McCarthy, Anne H. Cross, Tammie L. S. Benzinger, Robert T. Naismith, Salim Chahin
Summary: Brain age, quantified using machine learning applied to structural MRI, is a clinically relevant biomarker that correlates with and predicts increasing disability in patients with multiple sclerosis (MS).
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Cell Biology
Nicolas R. Barthelemy, Benjamin Saef, Yan Li, Brian A. Gordon, Yingxin He, Kanta Horie, Erik Stomrud, Gemma Salvado, Shorena Janelidze, Chihiro Sato, Vitaliy Ovod, Rachel L. Henson, Anne M. Fagan, Tammie L. S. Benzinger, Chengjie Xiong, John C. Morris, Oskar Hansson, Randall J. Bateman, Suzanne E. Schindler
Summary: CSF tau phosphorylation at T217 and T205 sites is a better marker for Alzheimer's disease pathology than current tests.
Article
Chemistry, Medicinal
Lin Qiu, Hao Jiang, Charles Zhou, Jinzhi Wang, Yanbo Yu, Haiyang Zhao, Tianyu Huang, Robert Gropler, Joel S. Perlmutter, Tammie L. S. Benzinger, Zhude Tu
Summary: This study reported the design, synthesis, and evaluation of novel F-18 S1PR1 radioligands. Compound 6h showed high selectivity and potency for S1PR1 and exhibited favorable brain washout pharmacokinetics in PET study. [18F]6h is a promising radioligand for imaging S1PR1 and worthy of further clinical investigation in brain disorders.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)