Article
Clinical Neurology
Priyanka Gorijala, M. Muaaz Aslam, Lam-Ha T. Dang, L. Xicota, Maria V. Fernandez, Yun Ju Sung, Kang-Hsien Fan, Eleanor Feingold, Ezequiel I. Surace, Jasmeer P. Chhatwal, Christy L. Hom, Sigan L. Hartley, Jason Hassenstab, Richard J. Perrin, Mark Mapstone, Shahid H. Zaman, Beau M. Ances, M. Ilyas Kamboh, Joseph H. Lee, Carlos Cruchaga
Summary: This study investigates the influence of Alzheimer's disease genetic architecture on Down syndrome status, cognitive measures, and cerebrospinal fluid biomarkers. The results suggest that the AD genetic architecture influences cognitive and CSF phenotypes in DS adults, supporting common pathways that influence memory decline in both traits.
ALZHEIMERS & DEMENTIA
(2023)
Article
Geriatrics & Gerontology
Devashi Paliwal, Tim W. McInerney, Judy Pa, Russell H. Swerdlow, Simon Easteal, Shea J. Andrews
Summary: Research shows a link between mitochondrial dysfunction and the pathogenesis of Alzheimer's disease. This study utilized polygenic risk scores to assess disease risk associated with biological pathways and found associations between the nuclear-encoded mitochondrial genome, three mitochondrial pathways, and increased AD risk. Therapeutic strategies targeting these pathways may have the potential to modify AD pathogenesis.
NEUROBIOLOGY OF AGING
(2021)
Article
Nutrition & Dietetics
Simon W. So, Kendra M. Fleming, Joshua P. Nixon, Tammy A. Butterick
Summary: Obesity, a known risk factor for Alzheimer's disease, increases microglial activation and inflammation. In this study, we found that a high fat diet led to neuroinflammation and cognitive decline in mice. The activation of brain microglia in obesity exacerbated AD pathology and increased the accumulation of amyloid beta plaques. Our results showed that a high fat diet decreased locomotor activity and increased anxiety-like behavior and behavioral despair. It also led to memory deficits and increased microgliosis and Aβ deposition in a young adult AD mouse model.
Article
Clinical Neurology
Jori Tomassen, Anouk den Braber, Sven J. van der Lee, Lianne M. Reus, Elles Konijnenberg, Stephen F. Carter, Maqsood Yaqub, Bart N. M. van Berckel, Lyduine E. Collij, Dorret I. Boomsma, Eco J. C. de Geus, Philip Scheltens, Karl Herholz, Betty M. Tijms, Pieter Jelle Visser
Summary: This study investigated the associations between APOE genotype, AD-Polygenic Risk Scores (AD-PRS), amyloid-beta pathology, and cognitive decline in cognitively unimpaired older individuals. The results showed that APOE genotype was related to memory and language decline only in individuals with abnormal amyloid-beta. Additionally, other genetic risk variants contributed to memory decline independently of amyloid-beta status in initially cognitively unimpaired older individuals.
Article
Neurosciences
Dandan Wang, Kai Xu, Mingxi Dang, Feng Sang, Kewei Chen, Zhanjun Zhang, Xin Li
Summary: Understanding the relationship between amyloid-beta accumulation and cognition is important for studying the pathology of Alzheimer's disease. This study examined the regional accumulation of amyloid-beta and its relationship with various cognitive functions. The results showed that amyloid-beta accumulation was mainly found in the frontoparietal cortex, calcarine fissure, and surrounding cortex and temporal pole regions. Support vector machine analysis indicated that episodic memory-related regions had better classification performance during the progression of Alzheimer's disease. Assessing regional changes in amyloid, particularly in the frontoparietal regions, can help in the early detection of cognitive decline related to amyloid.
Article
Neurosciences
Nicholas J. Schork, Jeremy A. Elman
Summary: By studying specific pathways associated with Alzheimer's disease, we can gain a better understanding of the disease's progression and risk factors. Pathway-specific polygenic risk scores may not have significant predictive power, but they can be useful in studying other complex diseases.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Clinical Neurology
Emma S. Luckett, Yasmina Abakkouy, Mariska Reinartz, Katarzyna Adamczuk, Jolien Schaeverbeke, Sare Verstockt, Steffi De Meyer, Koen Van Laere, Patrick Dupont, Isabelle Cleynen, Rik Vandenberghe
Summary: This study found that specific AD polygenic risk scores are associated with amyloid accumulation in the asymptomatic phase of Alzheimer's disease.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Geriatrics & Gerontology
Gyihyaon Yun, Hye Jin Kim, Hyug-Gi Kim, Kyung Mi Lee, Il Ki Hong, Sang Hoon Kim, Hak Young Rhee, Geon-Ho Jahng, Sung Sang Yoon, Key-Chung Park, Kyo Seon Hwang, Jin San Lee
Summary: The study found significant differences in plasma A beta (42/40) levels between the normal control group and Alzheimer's disease group, which best predicted the amyloid PET positivity. Higher levels of plasma A beta (42/40) were negatively correlated with verbal and visual memory performance.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Hakon Grydeland, Donatas Sederevicius, Yunpeng Wang, David Bartres-Faz, Lars Bertram, Valerija Dobricic, Sandra Duzel, Klaus P. Ebmeier, Ulman Lindenberger, Lars Nyberg, Sara Pudas, Claire E. Sexton, Cristina Sole-Padulles, Oystein Sorensen, Kristine B. Walhovd, Anders M. Fjell
Summary: This study found that poor sleep quality is associated with rapid decline in hippocampal microstructure and memory decay, especially in the presence of A beta accumulation. The results were not explained by genetic risk factors, suggesting that poor sleep efficiency may be a risk marker for AD.
Article
Clinical Neurology
Hakon Grydeland, Donatas Sederevicius, Yunpeng Wang, David Bartres-Faz, Lars Bertram, Valerija Dobricic, Sandra Duezel, Klaus P. Ebmeier, Ulman Lindenberger, Lars Nyberg, Sara Pudas, Claire E. Sexton, Cristina Sole-Padulles, Oystein Sorensen, Kristine B. Walhovd, Anders M. Fjell
Summary: The study found that poor sleep quality and low sleep efficiency were associated with a faster decline in hippocampal microstructure, especially in the presence of A beta accumulation. The decline in hippocampal integrity mediated the relationship between sleep efficiency and memory decay.
Article
Clinical Neurology
Jaeyoon Chung, Nathan Sahelijo, Toru Maruyama, Junming Hu, Rebecca Panitch, Weiming Xia, Jesse D. Mez, Thor J. Stein, Andrew J. Saykin, Haruko Takeyama, Lindsay A. Farrer, Paul K. Crane, Kwangsik Nho, Gyungah R. Jun
Summary: This study investigates the use of polygenic risk scores (PRSs) integrated with AD brain transcriptome profiles to explain clinical and neuropathological heterogeneity in AD. The findings indicate that two gene modules (M6 and M9) associated with NPs and NFTs are linked to language and visuospatial functioning, matching clinical subtypes and brain atrophy at specific regions.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Yuqing Sun, Meng Wang, Yuxin Zhao, Ke Hu, Yong Liu, Bing Liu
Summary: This study explored the potential of using specific polygenic risk scores (PRSs) as predictors of tau pathology and cognitive decline in non-demented individuals. The results showed that higher PRS was associated with elevated tau levels, greater rates of tau level changes, and memory impairment mediated by increased tau levels.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Neurosciences
Heba A. Ahmed, Saifudeen Ismael, Mohd Salman, Patrick Devlin, Michael P. McDonald, Francesca-Fang Liao, Tauheed Ishrat
Summary: Alzheimer's disease (AD) always coexists with vascular cognitive impairment (VCI), and vascular lesions can worsen the cognitive decline caused by AD. There is currently no satisfactory treatment for this irreversible neurodegenerative disease, emphasizing the need for safe and effective therapies. This study investigated the effects of long-term treatment with C21, an AT2R agonist, on mixed pathology cognitive impairment using a unique mouse model that combines AD and VCI. The results showed that C21 treatment preserved cognitive function, maintained cerebral blood flow, and reduced AD pathology.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Geriatrics & Gerontology
QinJie Li, Feng-Feng Pan, Qi Huang, Chun-Yi Zac Lo, Fang Xie, QiHao Guo
Summary: This study aimed to investigate metamemory alterations across the Alzheimer's continuum, the association between metamemory and cognition, and the relationship between cortical thickness in specific regions of interest and metamemory scores. Results showed that individuals with subjective cognitive decline (SCD) exhibited significantly higher degrees of confidence (DOC) in the A beta+ subgroup, and there was an increasing trend of overconfidence with cognitive decline across the AD spectrum.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Editorial Material
Genetics & Heredity
Clement A. Adebamowo, Adebowale Adeyemo, Adeyinka Ashaye, Onoja M. Akpa, Tinashe Chikowore, Ananyo Choudhury, Yasmina J. Fakim, Segun Fatumo, Neil Hanchard, Michael Hauser, Braxton Mitchell, Nicola Mulder, Solomon F. Ofori-Acquah, Mayowa Owolabi, Michele Ramsay, Bamidele Tayo, Archana Bhavani VasanthKumar, Yuji Zhang, Sally N. Adebamowo
Summary: The CARDINAL study site is a well-powered resource that aims to develop, refine, and validate methods for researching polygenic risk scores, taking into account local ancestry, to improve risk prediction in diverse populations.
Article
Clinical Neurology
Tingting Wang, Kevin Huynh, Corey Giles, Natalie A. Mellett, Thy Duong, Anh Nguyen, Wei Ling Florence Lim, Alex A. T. Smith, Gavriel Olshansky, Gemma Cadby, Joseph Hung, Jennie Hui, John Beilby, Gerald F. Watts, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Ashley Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Kevin Taddei, Vincent Dore, Juergen Fripp, Matthias Arnold, Gabi Kastenmueller, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Ralph N. Martins, Eric K. Moses, Rima Kaddurah-Daouk, Peter J. Meikle
Summary: The APOE genotype is strongly associated with late-onset Alzheimer's disease, with specific lipid species mediating up to 30% and 10% of the treatment effect of APOE epsilon 2 and epsilon 4, respectively. Plasma lipid species represent a potential therapeutic target for Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(2022)
Article
Geriatrics & Gerontology
Amy Woodfield, Tenielle Porter, Israa Gilani, Siti Noordin, Qiao-Xin Li, Steven Collins, Ralph N. Martins, Paul Maruff, Colin L. Masters, Christopher C. Rowe, Victor L. Villemagne, Vincent Dore, Philip Newsholme, Simon M. Laws, Giuseppe Verdile
Summary: Insulin resistance is implicated in Alzheimer's disease biomarker progression and cognitive decline. Cerebrospinal fluid (CSF) tau does not directly influence the association between insulin resistance and cognition, but CSF Aβ42 moderates the relationship between them.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Pratishtha Chatterjee, Steve Pedrini, James D. Doecke, Rohith Thota, Victor L. Villemagne, Vincent Dore, Abhay K. Singh, Penghao Wang, Stephanie Rainey-Smith, Christopher Fowler, Kevin Taddei, Hamid R. Sohrabi, Mark P. Molloy, David Ames, Paul Maruff, Christopher C. Rowe, Colin L. Masters, Ralph N. Martins
Summary: This study investigated the changes in several blood biomarkers across the AD continuum and their associations with cognitive decline and brain Aβ-PET load. The results showed that plasma Aβ1-42/Aβ1-40 ratio decreased, p-tau181 and GFAP increased in predicting the β-amyloid positive/negative status across the AD continuum.
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
Behavioral Sciences
Kelsey R. Sewell, Stephanie R. Rainey-Smith, Victor L. Villemagne, Jeremiah Peiffer, Hamid R. Sohrabi, Kevin Taddei, David Ames, Vincent Dore, Paul Maruff, Simon M. Laws, Colin L. Masters, Christopher C. Rowe, Ralph N. Martins, Kirk Erickson, Belinda M. Brown
Summary: The study suggests that physical activity may play a moderating role in the relationship between sleep, cognitive function, and brain A beta burden.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Review
Nutrition & Dietetics
Carolina B. Castro, Cintia B. Dias, Heidi Hillebrandt, Hamid R. Sohrabi, Pratishtha Chatterjee, Tejal M. Shah, Stephanie J. Fuller, Manohar L. Garg, Ralph N. Martins
Summary: This systematic review and meta-analysis examined the effects of medium-chain fatty acid (MCFA) supplementation on circulating ketone bodies and cognition in individuals with cognitive decline and Alzheimer's disease. The results showed that MCFA supplementation increases blood ketone levels and enhances brain energy metabolism. However, the effects on cognition varied and further research is needed to determine if MCFA-mediated increase in brain energy metabolism can improve cognition.
Article
Multidisciplinary Sciences
Nicholas W. G. Murray, Petra L. L. Graham, Paul F. F. Sowman, Greg Savage
Summary: Episodic memory deficits are common in aging and neurodegenerative disorders. Transcranial electrical stimulation (TES) is a promising tool for memory enhancement, but the optimal stimulation parameters are not yet determined. In a double-blind, randomized, sham-controlled study, applying TES over the left temporal lobe resulted in a decrease in word recall and an increase in memory errors compared to sham stimulation.
SCIENTIFIC REPORTS
(2023)
Article
Psychology, Educational
Thomas B. McGuckian, Peter H. Wilson, Rich D. Johnston, Shahin Rahimi-Golkhandan, Jan Piek, Dido Green, Jeffrey M. Rogers, Paul Maruff, Bert Steenbergen, Scott Ruddock
Summary: This longitudinal study examined the development of children's complex executive function (EF) using the Groton Maze Learning Task (GMLT). A total of 147 children (61 males, ages 5.5-11 years) were recruited from six multicultural primary schools in Melbourne and Perth, Australia. The study spanned from 2010 to 2012, with assessments on the GMLT conducted every 6 months. Growth curve models indicated a quadratic growth trajectory in each measure of error, reflecting visuospatial memory, executive control, and complex EF. The ability to apply rules for action, a key aspect of complex EF, developed rapidly during early-to-mid childhood.
Article
Neurosciences
Pratishtha Chatterjee, Vincent Dore, Steve Pedrini, Natasha Krishnadas, Rohith Thota, Pierrick Bourgeat, Milos D. Ikonomovic, Stephanie R. Rainey-Smith, Samantha C. Burnham, Christopher Fowler, Kevin Taddei, Rachel Mulligan, David Ames, Colin L. Masters, Jurgen Fripp, Christopher C. Rowe, Ralph N. Martins, Victor L. Villemagne
Summary: Astrocyte reactivity is associated with the elevation of plasma glial fibrillary acidic protein (GFAP) and monoamine oxidase-B (MAO-B) in Alzheimer's disease. The association between plasma GFAP and regional F-18-SMBT-1 PET is dependent on brain β-amyloid (Aβ) load.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Psychology, Clinical
Lisa Bransby, Emily Rosenich, Rachel F. Buckley, Nawaf Yassi, Matthew P. Pase, Paul Maruff, Yen Ying Lim
Summary: This study aimed to determine the frequency and co-occurrence of modifiable dementia risk factors (MDRFs) in a large sample of middle-aged adults. The results showed that most individuals reported MDRFs in two or more domains, and these multidomain MDRFs were related to poorer cognition.
Review
Behavioral Sciences
Andrea Brown, Sarah K. Salo, Greg Savage
Summary: This narrative synthesis summarizes the cognitive profiles of frontal variant Alzheimer's disease (fvAD) and highlights the need for further investigation into differential diagnostic markers, such as executive dysfunction and behavioral symptoms. It also reveals some similarities between fvAD and typical AD, which may guide future research in disease diagnosis.
Article
Clinical Neurology
John J. Alam, Paul Maruff, Susan R. Doctrow, Hui-May Chu, Jennifer Conway, Stephen N. Gomperts, Charlotte Teunissen
Summary: This study evaluates the relationship between plasma tau phosphorylated at residue 181 (ptau181), a biomarker of Alzheimer disease (AD) copathology, and the treatment effects of the p38 alpha kinase inhibitor neflamapimod in patients with dementia with Lewy bodies (DLB). The results suggest that DLB patients with lower pretreatment ptau181 levels may show better treatment response to neflamapimod, with improvement in attention, cognitive assessment, and daily functioning. Plasma biomarkers of AD copathology should be considered as stratification variables in DLB clinical trials.
Review
Neurosciences
Matin Ramezani, Malika Fernando, Shaun Eslick, Prita R. Asih, Sina Shadfar, Ekanayaka M. S. Bandara, Heidi Hillebrandt, Silochna Meghwar, Maryam Shahriari, Pratishtha Chatterjee, Rohith Thota, Cintia B. Dias, Manohar L. Garg, Ralph N. Martins
Summary: Alzheimer's disease is the most common form of dementia, characterized by cognitive dysfunction and behavioral changes. Pathological markers and neural damage in AD are associated with altered brain energy metabolism. The ketogenic diet has been shown to increase ketone body production, improving brain energy metabolism and potentially affecting AD biomarkers and neuroinflammation.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Geriatrics & Gerontology
Jun Yuan, Steve Pedrini, Rohith Thota, James Doecke, Pratishtha Chatterjee, Hamid R. Sohrabi, Charlotte E. Teunissen, Inge M. W. Verberk, Erik Stoops, Hugo Vanderstichele, Bruno P. Meloni, Christopher Mitchell, Stephanie Rainey-Smith, Kathryn Goozee, Andrew Chi Pang Tai, Nicholas Ashton, Henrik Zetterberg, Kaj Blennow, Junjie Gao, Delin Liu, Frank Mastaglia, Charles Inderjeeth, Minghao Zheng, Ralph N. Martins
Summary: This study investigated the association between plasma SOST levels and brain amyloid-beta load in older individuals. The results showed that plasma SOST levels were higher in individuals with brain amyloid-beta load, and the combination of plasma SOST and Aβ 42/Aβ40 ratio improved the predictive accuracy for preclinical Alzheimer's disease.
