Alison Headley1, Andres De Leon-Benedetti1, Chuanhui Dong1, Bonnie Levin1, David Loewenstein1, Christian Camargo1, Tatjana Rundek1, Henrik Zetterberg1, Kaj Blennow1, Clinton B Wright1, Xiaoyan Sun2. 1. From the Department of Neuroscience (A.H.), University of California San Diego, La Jolla; Department of Neurology (A.D.L.-B., C.D., B.L., C.C., T.R., X.S.), Evelyn F. McKnight Brain Institute (B.L., C.C., T.R., X.S.), and Psychiatry and Behavioral Sciences (D.L.), University of Miami Miller School of Medicine, FL; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University Gothenburg, Molndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute (H.Z.), London; and National Institute of Neurological Disorders and Stroke (C.B.W.), Bethesda, MD. 2. From the Department of Neuroscience (A.H.), University of California San Diego, La Jolla; Department of Neurology (A.D.L.-B., C.D., B.L., C.C., T.R., X.S.), Evelyn F. McKnight Brain Institute (B.L., C.C., T.R., X.S.), and Psychiatry and Behavioral Sciences (D.L.), University of Miami Miller School of Medicine, FL; Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University Gothenburg, Molndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute (H.Z.), London; and National Institute of Neurological Disorders and Stroke (C.B.W.), Bethesda, MD. XXS356@med.miami.edu.
Abstract
OBJECTIVE: To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). METHODS: Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. RESULTS: High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ42) were controlled for in these analyses. CONCLUSIONS: High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD.
OBJECTIVE: To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). METHODS: Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. RESULTS: High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ42) were controlled for in these analyses. CONCLUSIONS: High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD.
Authors: Laura E Gibbons; Adam C Carle; R Scott Mackin; Danielle Harvey; Shubhabrata Mukherjee; Philip Insel; S McKay Curtis; Dan Mungas; Paul K Crane Journal: Brain Imaging Behav Date: 2012-12 Impact factor: 3.978
Authors: Hlin Kvartsberg; Flora H Duits; Martin Ingelsson; Niels Andreasen; Annika Öhrfelt; Kerstin Andersson; Gunnar Brinkmalm; Lars Lannfelt; Lennart Minthon; Oskar Hansson; Ulf Andreasson; Charlotte E Teunissen; Philip Scheltens; Wiesje M Van der Flier; Henrik Zetterberg; Erik Portelius; Kaj Blennow Journal: Alzheimers Dement Date: 2014-12-19 Impact factor: 21.566
Authors: Jesse Mez; Shubhabrata Mukherjee; Timothy Thornton; David W Fardo; Emily Trittschuh; Sheila Sutti; Richard Sherva; John S Kauwe; Adam C Naj; Gary W Beecham; Alden Gross; Andrew J Saykin; Robert C Green; Paul K Crane Journal: Neurobiol Aging Date: 2016-02-21 Impact factor: 4.673
Authors: Alberto Garrido-García; Raquel de Andrés; Amanda Jiménez-Pompa; Patricia Soriano; Diego Sanz-Fuentes; Elena Martínez-Blanco; F Javier Díez-Guerra Journal: Mol Neurobiol Date: 2019-04-24 Impact factor: 5.590
Authors: Silke Kern; Jeremy A Syrjanen; Kaj Blennow; Henrik Zetterberg; Ingmar Skoog; Margda Waern; Clinton E Hagen; Argonde C van Harten; David S Knopman; Clifford R Jack; Ronald C Petersen; Michelle M Mielke Journal: JAMA Neurol Date: 2019-02-01 Impact factor: 18.302
Authors: Kaitlin Blackstone Casaletto; Henrik Zetterberg; Kaj Blennow; Ann Brinkmalm; William Honer; Julie A Schneider; David A Bennett; Nina Djukic; Michelle You; Sophia Weiner-Light; Corrina Fonseca; Bruce L Miller; Joel Kramer Journal: Neurology Date: 2021-05-04 Impact factor: 11.800
Authors: Andrew P Merluzzi; Nicholas M Vogt; Derek Norton; Erin Jonaitis; Lindsay R Clark; Cynthia M Carlsson; Sterling C Johnson; Sanjay Asthana; Kaj Blennow; Henrik Zetterberg; Barbara B Bendlin Journal: Alzheimers Dement (N Y) Date: 2019-04-12