Article
Clinical Neurology
Jing Wang, Siu Ping Lam, Bei Huang, Yaping Liu, Jihui Zhang, Mandy W. M. Yu, Jessie C. C. Tsang, Li Zhou, Steven W. H. Chau, Ngan Yin Chan, Joey W. Y. Chan, Carlos H. Schenck, Shirley X. Li, Vincent C. T. Mok, Karen Ka Yan Ma, Anne Yin Yan Chan, Yun Kwok Wing
Summary: Rapid eye movement (REM) sleep behaviour disorder (RBD) is an early and specific prodrome of a-synucleinopathies like Parkinson's disease (PD). It is unclear whether RBD occurring in the context of psychiatric disorders (psy-RBD) is merely a benign side effect of antidepressant treatment or has an underlying a-synucleinopathy. This study found that patients with psy-RBD have a familial predisposition to a-synucleinopathy.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Sonia Monge-Garcia, Maria-Salud Garcia-Ayllon, Jose Sanchez-Paya, Ruth Gasparini-Berenguer, Maria-Angeles Cortes-Gomez, Javier Saez-Valero, Jose-Antonio Monge-Argiles
Summary: This study evaluated the diagnostic validity of alpha-synuclein (AS) levels in the cerebrospinal fluid (CSF) as a predictor of psychotic symptoms (PS) in patients with mild cognitive impairment. The results showed that AS levels were able to differentiate between the psychotic and non-psychotic groups, achieving at least 80% sensitivity.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Simon Kang Seng Ting, Seyed Ehsan Saffari, Shahul Hameed, Hui Jin Chiew, Kok Pin Ng, Adeline S. L. Ng
Summary: In clinical practice, it is important to note that memory symptoms, although associated with a higher risk of AD diagnosis, are prominent in prodromal DLB. Psychosis is infrequent, and non-amnestic MCI is not necessarily associated with a higher risk of DLB diagnosis. A careful clinical approach is key to improve the diagnosis of prodromal DLB.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2023)
Article
Neuroimaging
Shubir Dutt, Yanrong Li, Mara Mather, Daniel A. Nation
Summary: The study found that in individuals with mild cognitive impairment, smaller midbrain and locus coeruleus volumes were associated with poorer attention and executive function, with the relationship between locus coeruleus volume and executive abilities remaining significant in those with Alzheimer's disease biomarkers. Brainstem volumes did not show significant correlation with memory processes in the study.
BRAIN IMAGING AND BEHAVIOR
(2021)
Article
Clinical Neurology
Tong Luo, Yun-Feng Tu, Shan Huang, Yuan-Yuan Ma, Qing-Hua Wang, Yan-Jiang Wang, Jun Wang
Summary: This study aimed to investigate the longitudinal impact of type 2 diabetes mellitus (T2DM) on the prodromal and dementia stages of Alzheimer's disease (AD), focusing on diabetes duration and other comorbidities. The study found that a longer duration of T2DM (≥5 years) was significantly associated with an increased risk of incident prodromal AD, but not with the risk of progression to AD dementia. The APOE e4 allele and comorbid coronary artery disease (CAD) further increased the risk of incident prodromal AD in patients with T2DM.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Review
Psychiatry
Giada Benasi, Giovanni A. Fava, Jenny Guidi
Summary: This systematic review examines prodromal symptoms of unipolar depression, finding that a distinct symptomatology exists before the onset of depression, characterized by anxiety, tension, irritability, and somatic complaints. The duration of the prodromal phase varies across studies, but remains consistent within individuals across different depressive episodes.
PSYCHOTHERAPY AND PSYCHOSOMATICS
(2021)
Article
Geriatrics & Gerontology
Chao Ren, Fen Wang, Kai-Jie He, Yu-Ting Zhang, Ling-Xi Li, Jin-Bao Zhang, Jing Chen, Cheng-Jie Mao, Chun-Feng Liu
Summary: Early-life stress can have long-term effects on human health, including the development of neurodegenerative diseases like Parkinson's disease. In this study, the researchers used a maternal separation model to explore the contribution of early-life stress to Parkinson's disease. They discovered behavioral, histochemical, neuromorphological, and transcriptional changes in rats that were separated from their mothers, providing new insights into the pathogenesis and potential therapies for Parkinson's disease related to depression.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Article
Clinical Neurology
Paola Salvatore, Ross J. Baldessarini, Harimandir K. Khalsa, Mauricio Tohen
Summary: The study analyzed psychopathological details of prodromes leading to first-lifetime psychotic episodes and found that these features could predict and distinguish final diagnoses of MDD, BD-I, and SzAffD. The findings highlight the value of early psychopathology in predicting final diagnoses of major affective and schizoaffective disorders.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Article
Cell Biology
Lorissa Lamoureux, Felecia M. Marottoli, Kuei Y. Tseng, Leon M. Tai
Summary: The study evaluated the role of APOE genotype in modulating seizures, finding that APOE4 is associated with higher incidence of tonic-clonic seizures and that FAD mutations impact seizure activity in a paradigm dependent manner.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
S. Hayley, F. Vahid-Ansari, H. Sun, P. R. Albert
Summary: Parkinson's disease is a complex illness influenced by environmental factors and genetic vulnerability. Many studies focus on the disease's motor symptoms and overlook the debilitating non-motor features that occur early in the disease process. Comorbid psychiatric features, such as clinical depression, anxiety, and sleep disorders, are believed to emerge before prominent motor deficits. This review explores the prodromal stage of PD, the unfolding of early neuropsychiatric pathology, and later motor disturbances, as well as the complexity captured by animal models of PD.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Leonardo Biscetti, Marco Lupidi, Elisa Luchetti, Paolo Eusebi, Ramkailash Gujar, Andrea Vergaro, Carlo Cagini, Lucilla Parnetti
Summary: This study compared retinal thickness and perfusion index in MCI-AD patients and cognitively healthy controls. Results showed a significant reduction in retinal vascular density and length in MCI-AD patients, but a higher fractal dimension, suggesting potential for early AD detection with OCT-A.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Health Care Sciences & Services
Mandana Fallahpour, Heather Fritz, Charlotta Thunborg, Ulrika Akenine, Miia Kivipelto
Summary: This study examined and described the active everyday lives of individuals with prodromal Alzheimer's disease. The findings identified key elements of participation quality that are important for rehabilitation and improving the quality of participation among individuals with cognitive impairments.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2022)
Article
Health Care Sciences & Services
Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti
Summary: Early diagnosis of Alzheimer's disease is crucial in disease management. Blood-based biomarkers, such as U-p53(2D3A8+), show promise as additional candidate biomarkers for AD diagnosis. Machine learning algorithms combining U-p53(2D3A8+) plasma levels with other markers can accurately predict AD likelihood risk and classify patients with aMCI who will develop AD.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Surgery
Fangyan Liu, Mei Duan, Huiqun Fu, Guoguang Zhao, Ying Han, Fei Lan, Zara Ahmed, Guanglei Cao, Zheng Li, Daqing Ma, Tianlong Wang
Summary: This study investigated gut microbiota and intestinal barrier function changes in elderly patients with either normal cognition or a prodromal Alzheimer disease phenotype after orthopedic surgery. The results showed that surgery exacerbated the preexisting microbiota dysbiosis and intestinal barrier dysfunction in prodromal Alzheimer disease patients, potentially leading to further cognitive deterioration.
Article
Clinical Neurology
Anders Gustavsson, Lars Lau Raket, Mathias Lilja, Loes Rutten-Jacobs, Hanna Fues Wahl, Marloes Bagijn, Erik Stomrud, Oskar Hansson, Sebastian Palmqvist
Summary: The study found that participants with prodromal AD (A beta-positive MCI) reported better health utility, while health utility in preclinical AD (A beta-positive CU) was similar to controls in the Swedish BioFINDER study.
ALZHEIMERS & DEMENTIA
(2021)
Article
Psychology, Clinical
Arthur Montalto, Haeme R. P. Park, Leanne M. Williams, Mayuresh S. Korgaonkar, Miranda R. Chilver, Javad Jamshidi, Peter R. Schofield, Justine M. Gatt
Summary: The study found that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention. This possibly suggests a pattern of 'neural efficiency' in people who may be more resilient to trauma.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Clinical Neurology
Haiyan Liu, Nicolas R. Barthelemy, Vitaliy Ovod, James G. Bollinger, Yingxin He, Samir L. Chahin, Brendan Androff, Randall J. Bateman, Brendan P. Lucey
Summary: Sleep deprivation increases cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels, while decreasing plasma levels. These findings suggest that sleep loss affects plasma biomarkers of Alzheimer's disease and should be taken into account when interpreting individual plasma biomarkers.
ALZHEIMERS & DEMENTIA
(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)
Review
Geriatrics & Gerontology
Krista L. Lanctot, Zahinoor Ismail, Kritleen K. Bawa, Jeffrey L. Cummings, Masud Husain, Moyra E. Mortby, Philippe Robert
Summary: This narrative review discusses the clinical features of apathy and depression in individuals with neurocognitive disorders, aiming to differentiate the two syndromes based on clinical presentation, diagnostic criteria, neuropathological features, and response to treatments.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Christopher H. van Dyck, Chad J. Swanson, Paul Aisen, Randall J. Bateman, Christopher Chen, Michelle Gee, Michio Kanekiyo, David Li, Larisa Reyderman, Sharon Cohen, Lutz Froelich, Sadao Katayama, Marwan Sabbagh, Bruno Vellas, David Watson, Shobha Dhadda, Michael Irizarry, Lynn D. Kramer, Takeshi Iwatsubo
Summary: Lecanemab, a humanized monoclonal antibody, reduced amyloid markers and showed improvement in cognition and function in early Alzheimer's disease patients. However, it also resulted in adverse events. Longer trials are needed to determine its efficacy and safety in early Alzheimer's disease.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Biology
Peter R. Millar, Brian A. Gordon, Patrick H. Luckett, Tammie L. S. Benzinger, Carlos Cruchaga, Anne M. Fagan, Jason J. Hassenstab, Richard J. Perrin, Suzanne E. Schindler, Ricardo F. Allegri, Gregory S. Day, Martin R. Farlow, Hiroshi Mori, Georg Nuebling, Randall J. Bateman, John C. Morris, Beau M. Ances
Summary: Estimates of 'brain-predicted age' quantify apparent brain age compared to normative trajectories of neuroimaging features. The brain age gap (BAG) between predicted and chronological age is elevated in symptomatic Alzheimer disease (AD) but has not been well explored in presymptomatic AD. Prior studies have typically modeled BAG with structural MRI, but more recently other modalities, including functional connectivity (FC) and multimodal MRI, have been explored.
Article
Pharmacology & Pharmacy
Jeffrey Cummings
Summary: Two anti-amyloid monoclonal antibodies, lecanemab (Leqembi) and aducanumab (Aduhelm), have been approved in the USA for the treatment of Alzheimer's disease. These breakthrough agents slow the clinical decline of AD by targeting the disease's basic biological processes, supporting the amyloid hypothesis and amyloid as a target for drug development. Monoclonal antibodies bring about a new era in AD therapy and open doors for the development of treatments for various neurodegenerative disorders.
Review
Psychology, Clinical
Mary Sano, Jeffrey Cummings, Stefanie Auer, Sverre Bergh, Corinne E. Fischer, Debby Gerritsen, George Grossberg, Zahinoor Ismail, Krista Lanctot, Maria I. Lapid, Jacobo Mintzer, Rebecca Palm, Paul B. Rosenberg, Michael Splaine, Kate Zhong, Carolyn W. Zhu
Summary: This article summarizes the use and validation of the provisional consensus definition of agitation in cognitive disorders published by the International Psychogeriatric Association (IPA) in 2015. It presents a finalized definition based on the review of academic literature, clinical guidelines, expert surveys, and patient and family advocates' experiences. The article also discusses the development of diagnostic tools and strategies for dissemination and integration of the definition into precision diagnosis and agitation interventions.
INTERNATIONAL PSYCHOGERIATRICS
(2023)
Review
Psychology, Clinical
Jeffrey Cummings, Mary Sano, Stefanie Auer, Sverre Bergh, Corinne E. Fischer, Debby Gerritsen, George Grossberg, Zahinoor Ismail, Krista Lanctot, Maria I. Lapid, Jacobo Mintzer, Rebecca Palm, Paul B. Rosenberg, Michael Splaine, Kate Zhong, Carolyn W. Zhu
Summary: The IPA Agitation Work Group develops an algorithm for reducing and preventing agitation, which emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches, and shared decision-making. The algorithm includes different treatment choices for different levels of agitation.
INTERNATIONAL PSYCHOGERIATRICS
(2023)
Review
Biochemistry & Molecular Biology
Ramakrishna Nirogi, Pradeep Jayarajan, Anil Shinde, Abdul Rasheed Mohammed, Venkata Ramalingayya Grandhi, Vijay Benade, Vinod Kumar Goyal, Renny Abraham, Venkat Jasti, Jeffrey Cummings
Summary: Serotonin-6 (5-HT6) receptor, a G-protein-coupled receptor, plays a key role in the regulation of various functions in the nervous system. Clinical studies have shown that 5-HT6 receptor antagonists have potential in treating cognitive deficits associated with Alzheimer's disease (AD) and neuropsychiatric symptoms in dementia. However, the outcomes of phase 3 trials for these antagonists have been disappointing. Masupirdine, a selective 5-HT6 receptor antagonist, has shown promise in reducing agitation/aggression-like behaviors in animal models and may have potential benefits for agitation and psychosis in AD, but further trials are needed.
Review
Pharmacology & Pharmacy
Jeffrey L. Cummings, Amanda M. Leisgang Osse, Jefferson W. Kinney
Summary: Novel agents targeting non-amyloid, non-tau proteins in Alzheimer's Disease (AD) account for 70% of the drugs currently in clinical trials. Inflammation and synaptic plasticity/neuroprotection are the most common categories for novel therapies in AD research. Multiple categories, including APOE4 effects, lipids and lipoprotein receptors, neurogenesis, and oxidative stress, are being evaluated. Biomarkers are evolving in parallel with new targets and novel agents, providing a means of supporting disease modification. The identification and development of novel targets offer an important opportunity for advancing new AD treatments.
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
Cell Biology
Jinbin Xu, Huifangjie L. Farsad, Yiran Hou, Kia Barclay, Ben Anthony Lopez, Shinnosuke Yamada, Ibrahim Olabayode Saliu, Yiming Shi, William C. Knight, Randall J. Bateman, Tammie L. S. Benzinger, Jason J. Yi, Qingyun Li, Ting Wang, Joel S. Perlmutter, John C. Morris, Guoyan Zhao
Summary: Zhao et al. discovered evolutionarily conserved astrocyte and microglia subpopulations shared across multiple brain regions, revealing similarities and differences in AD and PD glia and regional variance linked to AD pathology and neurodegeneration. Their analysis identified commonalities between AD and PD astrocytes and unique transcriptomic changes in microglia for each disorder. They also delineated undescribed subpopulations of medium spiny neurons (MSNs) and provided neuronal transcriptomic profiles suggesting disease-specific changes and selective vulnerability.
Correction
Neurosciences
Jigyasha Timsina, Duber Gomez-Fonseca, Lihua Wang, Anh Do, Dan Western, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, Rachel L. Henson, Elizabeth Herries, Chengjie Xiong, Suzanne E. Schindler, Anne M. Fagan, Randall J. Bateman, Martin Farlow, John C. Morris, Richard J. Perrin, Krista Moulder, Jason Hassenstab, Jonathan Voeglein, Jasmeer Chhatw, Hiroshi Mori, Yun Ju Sung, Carlos Cruchaga
JOURNAL OF ALZHEIMERS DISEASE
(2023)