Journal of Neurology

, Volume 257, Issue 12, pp 2078–2085

Cortical excitability in very mild Alzheimer’s disease: a long-term follow-up study

Original Communication

Abstract

Measurement of motor cortex excitability using paired-pulse transcranial magnetic stimulation (pTMS) has been proposed for the early diagnosis of Alzheimer’s disease (AD) and could also be useful for monitoring treatment response and disease progression. However, studies conducted at the pre-dementia stage of AD are scarce, very few long-term data are available, and correlations between cortical excitability and cognitive performance have not been addressed. Eleven patients with mild cognitive impairment (MCI) that converted to AD-related dementia and 12 elderly control subjects were selected for this study. Cognitive assessments and pTMS were conducted at baseline in the two groups and also after 4 and 21 months of treatment with donepezil in the AD group. Non-parametric statistics were used to compare cortical excitability between the two study groups at baseline and to analyse disease course in the AD group. Correlation analysis was performed to investigate associations between cortical excitability and cognitive performance. Short-latency intracortical inhibition (SICI) and intracortical facilitation were reduced in AD patients. However, there was high inter-individual variability, and statistical significance was only attained at a 2-ms interstimulus interval (ISI). A trend towards recovery of 2-ms SICI was observed after treatment with donepezil. Baseline cortical excitability at 300 ms was associated with better cognitive performance in AD patients. Although the present results do not support a role for pTMS in the early diagnosis of late-onset AD, a potential role in prediction of treatment response and understanding of disease mechanisms emerged.

Keywords

Cortical excitability Alzheimer’s disease Paired-pulse transcranial magnetic stimulation Mild cognitive impairment 

Supplementary material

415_2010_5663_MOESM1_ESM.doc (133 kb)
Supplementary material 1 (DOC 133 kb)

References

  1. 1.
    De Carvalho M, de Mendonça A, Miranda PC, Garcia C, Luís ML (1997) Magnetic stimulation in Alzheimer’s disease. J Neurol 244:304–307CrossRefPubMedGoogle Scholar
  2. 2.
    Alagona G, Bella R, Ferri R, Carnemolla A, Pappalardo A, Costanzo E, Pennisi G (2001) Transcranial magnetic stimulation in Alzheimer disease: motor cortex excitability and cognitive severity. Neurosci Lett 314:57–60CrossRefPubMedGoogle Scholar
  3. 3.
    Ferreri F, Pauri F, Pasqualetti P, Fini R, Dal Forno G, Rossini PM (2003) Motor cortex excitability in Alzheimer’s disease: a transcranial magnetic stimulation study. Ann Neurol 53:102–108CrossRefPubMedGoogle Scholar
  4. 4.
    Valls-Solé J, Pascual-Leone A, Wassermann EM, Hallett M (1992) Human motor evoked responses to paired transcranial magnetic stimuli. Electroencephalogr Clin Neurophysiol 85:355–364CrossRefPubMedGoogle Scholar
  5. 5.
    Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A et al (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519PubMedGoogle Scholar
  6. 6.
    Abbruzzese G, Trompetto C (2002) Clinical and research methods for evaluating cortical excitability. J Clin Neurophysiol 19:307–321CrossRefPubMedGoogle Scholar
  7. 7.
    Liepert J, Bär KJ, Meske U, Weiller C (2001) Motor cortex disinhibition in Alzheimer’s disease. Clin Neurophysiol 112:1436–1441CrossRefPubMedGoogle Scholar
  8. 8.
    Pierantozzi M, Panella M, Palmieria MG, Kocha G, Giordano A, Marciania MG et al (2004) Different TMS patterns of intracortical inhibition in early onset Alzheimer dementia and frontotemporal dementia. Clin Neurophysiol 115:2410–2418PubMedGoogle Scholar
  9. 9.
    Pepin JL, Bogacz D, de Pasqua V, Delwaide PJ (1999) Motor cortex inhibition is not impaired in patients with Alzheimer’s disease: evidence from paired transcranial magnetic stimulation. J Neurol Sci 170:119–123CrossRefPubMedGoogle Scholar
  10. 10.
    Di Lazzaro V, Oliviero A, Pilato F, Saturno E, Dileone M, Marra C et al (2004) Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 75:555–559CrossRefPubMedGoogle Scholar
  11. 11.
    Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV et al (2001) Current concepts in mild cognitive impairment. Arch Neurol 58:1985–1992CrossRefPubMedGoogle Scholar
  12. 12.
    Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J et al (2007) Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 6:734–746CrossRefPubMedGoogle Scholar
  13. 13.
    Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M et al (2008) Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 148:379–397PubMedGoogle Scholar
  14. 14.
    Raschetti R, Albanese E, Vanacore N, Maggini M (2007) Cholinesterase inhibitors in mild cognitive impairment: a systematic review of randomised trials. PLoS Med 4:e338CrossRefPubMedGoogle Scholar
  15. 15.
    Zaborszky L, Duque A (2000) Local synaptic connections of basal forebrain neurons. Behav Brain Res 115:143–158CrossRefPubMedGoogle Scholar
  16. 16.
    Hughes CP, Berg L, Danziger WL, Coben LA, Martin RL (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140:566–572CrossRefPubMedGoogle Scholar
  17. 17.
    American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders (4th edn, text revision) DSM-IV-TR. American Psychiatric Association, WashingtonCrossRefGoogle Scholar
  18. 18.
    Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMedGoogle Scholar
  19. 19.
    Rosen WG, Mohs RC, Davis KL (1984) A new rating scale for Alzheimer’s disease. Am J Psychiatry 141:1356–1364PubMedGoogle Scholar
  20. 20.
    McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944PubMedGoogle Scholar
  21. 21.
    Rothman KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1:43–46CrossRefPubMedGoogle Scholar
  22. 22.
    Lang N, Hasan A, Sueske E, Paulus W, Nitsche MA (2008) Cortical hypoexcitability in chronic smokers? A transcranial magnetic stimulation study. Neuropsychopharmacology 33:2517–2523CrossRefPubMedGoogle Scholar
  23. 23.
    Di Lazzaro V, Oliviero A, Tonali PA, Marra C, Daniele A, Profice P et al (2002) Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation. Neurology 59:392–397PubMedGoogle Scholar
  24. 24.
    Nardone R, Bergmann J, Kronbichler M, Kunz A, Klein S, Caleri F et al (2008) Abnormal short latency afferent inhibition in early Alzheimer’s disease: a transcranial magnetic demonstration. J Neural Transm 115:1557–1562CrossRefPubMedGoogle Scholar
  25. 25.
    Sakuma K, Murakami T, Nakashima K (2007) Short latency afferent inhibition is not impaired in mild cognitive impairment. Clin Neurophysiol 118:1460–1463CrossRefPubMedGoogle Scholar
  26. 26.
    Scarmeas N, Stern Y (2003) Cognitive reserve and lifestyle. J Clin Exp Neuropsychol 25:625–633CrossRefPubMedGoogle Scholar
  27. 27.
    Pettersson AF, Olsson E, Wahlund LO (2005) Motor function in subjects with mild cognitive impairment and early Alzheimer’s disease. Dement Geriatr Cogn Disord 19:299–304CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • J. Olazarán
    • 1
    • 2
    • 4
  • J. Prieto
    • 3
  • I. Cruz
    • 1
  • A. Esteban
    • 3
  1. 1.Neurology ServiceGregorio Marañón General University HospitalMadridSpain
  2. 2.Neurology ClinicHermanos Sangro Specialties ClinicMadridSpain
  3. 3.Clinical Neurophysiology ServiceGregorio Marañón General University HospitalMadridSpain
  4. 4.Servicio de NeurologíaHGU Gregorio MarañónMadridSpain

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