Related Experiment Video
Updated: Aug 20, 2025
Transcranial Pulse Stimulation for Alzheimer's Patients
Published on: April 4, 2025
Preliminary Evidence that Memantine Enhances Prepulse Effects on Startle Magnitude and Latency in Patients with
Neal R Swerdlow1,2, Yash B Joshi1,2, Joyce Sprock1,2
1Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, CA, USA.
Background:
The uncompetitive NMDA antagonist, memantine (MEM), enhances prepulse inhibition of startle (PPI) across species. MEM is used to treat Alzheimer's disease (AD); conceivably, its acute impact on PPI might be used to predict a patient's sensitivity to MEM's therapeutic effects.
Objective:
To begin to test this possibility, we studied MEM effects on PPI and related measures in AD patients.
Methods:
18 carefully screened individuals with AD (mean age = 72.8 y; M:F=9 : 9) completed double-blind order-balanced testing with MEM (placebo versus 20 mg), assessing acoustic startle magnitude, habituation, PPI, and latency.
Results:
Fifteen out of 18 participants exhibited reliable startle responses. MEM did not significantly impact startle magnitude or habituation. Compared to placebo responses, PPI was significantly increased after MEM (p < 0.04; d = 0.40); this comparison reached a large effect size for the 60 ms interval (d = 0.62), where maximal MEM effects on PPI were previously detected. Prepulses reduced peak startle latency ("latency facilitation") and this effect was amplified after MEM (p = 0.03; d = 0.41; for 60 ms intervals, d = 0.69). No effects of MEM were detected on cognition, nor were MEM effects on startle associated with cognitive or clinical measures.
Conclusion:
MEM enhances prepulse effects on startle magnitude and latency in AD; these changes in PPI and latency facilitation with MEM suggest that these measures can be used to detect an AD patient's neural sensitivity to acute MEM challenge. Studies in progress will determine whether such a "biomarker" measured at the outset on treatment can predict sensitivity to MEM's therapeutic effects.
Insights
Memantine (MEM) enhances prepulse inhibition of startle (PPI) and latency facilitation in Alzheimer's disease (AD) patients. These findings suggest MEM's effects on startle measures may predict therapeutic sensitivity.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Memantine (MEM), an uncompetitive NMDA antagonist, is used to treat Alzheimer's disease (AD).
- MEM has been shown to enhance prepulse inhibition of startle (PPI) across species.
- Acute effects of MEM on PPI could potentially predict patient response to therapy.
Purpose of the Study:
- To investigate the effects of memantine on PPI and related startle measures in patients with Alzheimer's disease.
- To explore the potential of using MEM-induced changes in PPI as a biomarker for therapeutic sensitivity in AD.
Main Methods:
- 18 individuals with AD underwent double-blind, placebo-controlled testing with memantine (20 mg).
- Assessments included acoustic startle magnitude, habituation, PPI, and latency.
- Data were analyzed for significant differences between memantine and placebo conditions.
Main Results:
- Memantine significantly increased PPI (p < 0.04) and amplified latency facilitation (p = 0.03) in AD patients.
- The effect on PPI was particularly pronounced at the 60 ms interval (d = 0.62).
- No significant impact on startle magnitude or habituation was observed; cognitive effects were not detected.
Conclusions:
- Memantine enhances prepulse effects on startle magnitude and latency in Alzheimer's disease patients.
- These observed changes in PPI and latency facilitation suggest potential as biomarkers for neural sensitivity to acute memantine.
- Further research is ongoing to determine if these "biomarker" measures can predict therapeutic response to memantine in AD.
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