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Am J Geriatr Psychiatry. 2016 Nov;24(11):1028-1039. doi: 10.1016/j.jagp.2016.04.013. Epub 2016 May 4.

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.

Author information

1
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.
2
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.
3
Department of Psychiatry, The Jikei University School of Medicine, Tokyo, Japan.
4
Cerebral Imaging Centre, Douglas Mental Health Institute, McGill University, Montreal, Quebec, Canada; Department of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec, Canada.
5
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.
6
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.
7
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.
8
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.

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; GABA-A; benzodiazepine; cognition; function; β-amyloid

PMID:
27538351
DOI:
10.1016/j.jagp.2016.04.013
[Indexed for MEDLINE]

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