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

Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective 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. Methods 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. Results 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). Conclusion 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.

Original languageEnglish
Pages (from-to)1028-1039
Number of pages12
JournalAmerican Journal of Geriatric Psychiatry
Volume24
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1

Fingerprint

Benzodiazepines
Amyloid
Positron-Emission Tomography
Cognition
Aminobutyrates
Verbal Learning
Cognitive Dysfunction
florbetapir
Neuroimaging
Antidepressive Agents
Canada
Psychiatry
Alzheimer Disease
Research Design
Cross-Sectional Studies
Prospective Studies
Population

Keywords

  • Alzheimer disease
  • benzodiazepine
  • cognition
  • function
  • GABA-A
  • β-amyloid

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

@article{cf2f3d253fc74ed99dc13ab51e0352a2,
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 = "Objective 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. Methods 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. Results 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). Conclusion 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.",
keywords = "Alzheimer disease, benzodiazepine, cognition, function, GABA-A, β-amyloid",
author = "{Alzheimer's Disease Neuroimaging Initiative} and Chung, {Jun Ku} and Shinichiro Nakajima and Shunichiro Shinagawa and Eric Plitman and Chakravarty, {M. Mallar} and Yusuke Iwata and Fernando Caravaggio and Pollock, {Bruce G.} and Philip Gerretsen and Ariel Graff-Guerrero",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.jagp.2016.04.013",
language = "English",
volume = "24",
pages = "1028--1039",
journal = "American Journal of Geriatric Psychiatry",
issn = "1064-7481",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Benzodiazepine Use Attenuates Cortical β-Amyloid and is Not Associated with Progressive Cognitive Decline in Nondemented Elderly Adults

T2 - A Pilot Study Using F18-Florbetapir Positron Emission Tomography

AU - Alzheimer's Disease Neuroimaging Initiative

AU - Chung, Jun Ku

AU - Nakajima, Shinichiro

AU - Shinagawa, Shunichiro

AU - Plitman, Eric

AU - Chakravarty, M. Mallar

AU - Iwata, Yusuke

AU - Caravaggio, Fernando

AU - Pollock, Bruce G.

AU - Gerretsen, Philip

AU - Graff-Guerrero, Ariel

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Objective 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. Methods 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. Results 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). Conclusion 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.

AB - Objective 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. Methods 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. Results 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). Conclusion 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.

KW - Alzheimer disease

KW - benzodiazepine

KW - cognition

KW - function

KW - GABA-A

KW - β-amyloid

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U2 - 10.1016/j.jagp.2016.04.013

DO - 10.1016/j.jagp.2016.04.013

M3 - Article

VL - 24

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EP - 1039

JO - American Journal of Geriatric Psychiatry

JF - American Journal of Geriatric Psychiatry

SN - 1064-7481

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