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
N1 - Funding Information:
Mr. Chung received Canada Graduate Scholarship Master's award from the Canadian Institutes of Health Research (CIHR). Dr. Nakajima has received fellowship grants from the CIHR, Japan Society for the Promotion of Science, and Nakatomi Foundation and manuscript fees from Dainippon Sumitomo Pharma and Kyowa Hakko Kirin. Dr. Iwata has received manuscript fees from Dainippon Sumitomo Pharma and Wiley Japan within the past 3 years. Mr. Plitman received CIHR funds and an Ontario Gradudate Scholarship. Dr. Gerretsen has received Centre for Addiction and Mental Health CIHR and Ontario Mental Health Foundation fellowships. Ariel Graff-Guerrero has received a grant from the CIHR (MOP-97946). These grant agencies did not influence study design, data acquisition and analysis, or journal selection for submission. Other authors have nothing to disclose.
Publisher Copyright:
© 2016 American Association for Geriatric Psychiatry
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 - GABA-A
KW - benzodiazepine
KW - cognition
KW - function
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
C2 - 27538351
AN - SCOPUS:84992209043
SN - 1064-7481
VL - 24
SP - 1028
EP - 1039
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 11
ER -