Benzodiazepine Use Attenuates Cortical β-Amyloid and is Not Associated with Progressive Cognitive Decline in Nondemented Elderly Adults: A Pilot Study Using F 18-Florbetapir Positron Emission Tomography

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Benzodiazepines / therapeutic use*
  • Case-Control Studies
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / metabolism
  • Cognitive Dysfunction / epidemiology*
  • Cross-Sectional Studies
  • Ethylene Glycols
  • Female
  • Fluorine Radioisotopes
  • Follow-Up Studies
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / metabolism
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / metabolism
  • Humans
  • Male
  • Neuropsychological Tests
  • Parietal Lobe / diagnostic imaging
  • Parietal Lobe / metabolism
  • Pilot Projects
  • Positron-Emission Tomography
  • Prospective Studies
  • Regression Analysis
  • Risk Factors
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / metabolism

Substances

  • Amyloid beta-Peptides
  • Aniline Compounds
  • Ethylene Glycols
  • Fluorine Radioisotopes
  • Benzodiazepines
  • florbetapir