Neurophysiological predictors of long term response to AChE inhibitors in AD patients.
BACKGROUND
In vivo evaluation of cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI). SAI is reduced in Alzheimer's disease (AD) and drugs enhancing cholinergic transmission increase SAI.


METHODS
We evaluated whether SAI testing, together with SAI test-retest, after a single dose of the acetylcholinesterase (AChE) inhibitor rivastigmine, might be useful in predicting the response after 1 year treatment with rivastigmine in 16 AD patients.


RESULTS
Fourteen AD patients had pathologically reduced SAI. SAI was increased after administration of a single oral dose of rivastigmine in AD patients with abnormal baseline SAI, but individual responses to rivastigmine varied widely, with SAI change ranging from an increase in inhibition of approximately 50% of test size to no change. Baseline SAI and the increase in SAI after a single dose of rivastigmine were correlated with response to long term treatment. A normal SAI in baseline conditions, or an abnormal SAI in baseline conditions that was not greatly increased by a single oral dose of rivastigmine, were invariably associated with poor response to long term treatment, while an abnormal SAI in baseline conditions in conjunction with a large increase in SAI after a single dose of rivastigmine was associated with good response to long term treatment in most of the patients.


CONCLUSIONS
Evaluation of SAI may be useful for identifying AD patients likely to respond to treatment with AChE inhibitors.
Di Lazzaro
V
V
Institute of Neurology, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy. vdilazzaro@rm.unicatt.it
Oliviero
A
A
Pilato
F
F
Saturno
E
E
Dileone
M
M
Marra
C
C
Ghirlanda
S
S
Ranieri
F
F
Gainotti
G
G
Tonali
P
P
D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D004334:Drug Administration Schedule; D055590:Electromagnetic Phenomena / Q000295:instrumentation; D005500:Follow-Up Studies; D006801:Humans; D009044:Motor Cortex / Q000187:drug effects / Q000473:pathology; D009433:Neural Inhibition / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D009483:Neuropsychological Tests; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D011446:Prospective Studies; D000068836:Rivastigmine; D012720:Severity of Illness Index; D013995:Time
D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000068836:Rivastigmine