title: Benzodiazepine Use Attenuates Cortical β-Amyloid and is Not Associated with Progressive Cognitive Decline in Nondemented Elderly Adults: A Pilot Study Using F18-Florbetapir Positron Emission Tomography.
abstract: It is inconclusive as to whether benzodiazepines (BZDs) are related to cognitive deterioration in the elderly populations. Animal studies suggest that γ-aminobutyric acid A receptor agonists, such as BZDs, may prevent Aβ-neurotoxicity and reduce β-amyloid (Aβ). However, no studies have investigated the effects of BZD use on Aβ in humans.
  
  
  
  This cross-sectional, prospective study using Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada on nondemented elderly adults between 55 and 90 years of age assessed cortical Aβ levels by positron emission tomography radiotracer F18-Florbetapir. Changes in global cognitive function and verbal memory performance over 2 years were assessed using scores on Montreal Cognitive Assessment and five domains of Rey Auditory Verbal Learning Test, respectively.
  
  
  
  Previous BZD users (N = 15) had lower cortical Aβ levels in frontal (F(1, 26) = 8.82, p = 0.006), cingulate (F(1, 26) = 8.58, p = 0.007), parietal (F(1, 26) = 7.31, p = 0.012), and temporal (F(1, 26) = 7.67, p = 0.010) regions compared with matched BZD nonusers (N = 15), after controlling for history of psychiatric disorders and antidepressant use. Also, no differences were found in global cognitive function and changes in cortical Aβ over 2 years between continuous BZD users (N = 15) andthe matched nonuser group (N = 15).
  
  
  
  Previous BZD use was associated with lower cortical Aβ levels in nondemented elderly control subjects. Future studies with larger samples are required to replicate our findings.
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Jun Ku
authors.initials: JK
authors.lastname: Chung
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Shinagawa
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Plitman
authors.affiliation: Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec, Canada.
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group-Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: ariel.graff@camh.ca.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001569:Benzodiazepines / Q000627:therapeutic use*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D005026:Ethylene Glycols; D005260:Female; D005462:Fluorine Radioisotopes; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005026:Ethylene Glycols; D005462:Fluorine Radioisotopes; D001569:Benzodiazepines; C545186:florbetapir
keywords: Alzheimer disease; GABA-A; benzodiazepine; cognition; function; β-amyloid