J Neurol Neurosurg Psychiatry 76:1064-1069 doi:10.1136/jnnp.2004.051334
  • Paper

Neurophysiological predictors of long term response to AChE inhibitors in AD patients

  1. V Di Lazzaro1,
  2. A Oliviero1,
  3. F Pilato1,
  4. E Saturno1,
  5. M Dileone1,
  6. C Marra1,
  7. S Ghirlanda2,
  8. F Ranieri1,
  9. G Gainotti1,
  10. P Tonali1
  1. 1Institute of Neurology, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy
  2. 2Department of Psychology, Università di Bologna, Viale Berti-Pichat 5, Bologna, Italy
  1. Correspondence to:
 Vincenzo Di Lazzaro
 Istituto di Neurologia, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy;
  • Received 5 August 2004
  • Accepted 26 November 2004
  • Revised 26 November 2004


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 ∼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.


  • This work was supported by the Ministero della Sanità (Programma di ricerca finalizzata – Malattia di Alzheimer, 2000 – Regione Lazio Assessorato per le Politiche della Sanità and Programma di ricerca finalizzata – Memoria ed apprendimento motorio dalla fisiopatologia cellulare del danno neurale sperimentale alle nuove tecniche diagnostiche 2003).

  • Competing interests: none declared

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