Skip to main content

Advertisement

Log in

Effectiveness of treatment with donepezil hydrochloride and changes in regional cerebral blood flow in patients with Alzheimer's disease

  • ORIGINAL ARTICLE
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

Objective

The objective of this study was to elucidate the relationship between the effects of donepezil hydrochloride (donepezil) and cerebral blood flow, and to evaluate the usefulness of cerebral blood flow imaging in assessing and predicting treatment effectiveness.

Methods

The subjects were 29 outpatients (12 men and 17 women; age 50–82 years; mean age 69.2 years), who had received a diagnosis of Alzheimer's disease (AD). Efficacy was evaluated before donepezil administration; after 1 month, 3 months, and 6 months of drug administration; and at 1 year after completion of administration using the Japanese version of the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog), as a measure of cognitive function. The ADAS-cog has been frequently used to evaluate cognitive function in AD patients. Patients whose ADAS-cog scores improved by 3 or more points during the observation period were classified as responders, and those with no improvement were classified as nonresponders. 123I-IMP was used for single photon emission computed tomography cerebral blood flow scintigraphy.

Results

On the basis of ADAS-cog score improvement, 22 of the 29 patients were responders (7 men and 15 women; age 50–82 years; mean age 69.0 years) and seven were nonresponders (5 men and 2 women; age 61–80 years; mean age 70.0 years). The results indicate that a difference in cerebral blood flow responsiveness after 1 month of treatment distinguishes responders from nonresponders. After 1 month, blood flow was significantly decreased in all regions of nonresponders, whereas significant increases in blood flow were seen in the anterior frontal lobe and parietal lobe of responders. At that time point, blood flow in the basal ganglion differed significantly between the two groups, indicating that this difference in responsiveness after 1 month of treatment may distinguish responders from nonresponders.

Conclusions

In cognitive function testing, the group that exhibited a complete response showed improvement primarily in parameters reflecting frontal lobe function. Complete responders also showed significantly greater blood flow increases in the basal ganglion and thalamus early during the treatment period. This indicates that the drug responsiveness of the basal ganglion and thalamus affects frontal lobe function and distinguishes complete responders from patients who do not exhibit such a response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. M Dooley HM Lamb (2000) ArticleTitleDonepezil: a review of its use in Alzheimer's disease Drugs Aging 16 199–226 Occurrence Handle10803860 Occurrence Handle10.2165/00002512-200016030-00005 Occurrence Handle1:CAS:528:DC%2BD3cXisFeqsLo%3D

    Article  PubMed  CAS  Google Scholar 

  2. H Hara A Monsonego K Yuasa K Adachi X Xiao S Takeda et al. (2004) ArticleTitleDevelopment of a safe oral A beta vaccine using recombinant adeno-associated virus vector for Alzheimer's disease J Alzheimers Dis 6 483–8 Occurrence Handle15505369 Occurrence Handle1:CAS:528:DC%2BD2cXoslemtrc%3D

    PubMed  CAS  Google Scholar 

  3. RS Hellman RS Tikofsky BD Collier RG Hoffmann DW Palmer SL Glatt et al. (1989) ArticleTitleAlzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging Radiology 172 183–8 Occurrence Handle2787034 Occurrence Handle1:STN:280:BiaB1MjjvVc%3D

    PubMed  CAS  Google Scholar 

  4. H Iida H Itoh M Nakazawa J Hatazawa H Nishimura Y Onishi et al. (1994) ArticleTitleQuantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT J Nucl Med 35 2019–30 Occurrence Handle7989987 Occurrence Handle1:STN:280:ByqD1c7os1Q%3D

    PubMed  CAS  Google Scholar 

  5. R Takeuchi Y Yonekura H Matsuda J Konishi (2002) ArticleTitleUsefulness of a three-dimensional stereotaxic ROI template for an anatomically standardized 99mTc-ECD-SPET Eur J Nucl Med Imaging 29 331–41 Occurrence Handle10.1007/s00259-001-0715-z Occurrence Handle1:CAS:528:DC%2BD38XhvVCmsrc%3D

    Article  CAS  Google Scholar 

  6. S Minoshima KA Frey RA Koeppe NL Foster DE Kuhl (1995) ArticleTitleA diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18 J Nucl Med 36 1238–48 Occurrence Handle7790950 Occurrence Handle1:STN:280:ByqA3M7gtlM%3D

    PubMed  CAS  Google Scholar 

  7. KJ Friston AP Holmes KJ Worsley JB Poline CD Frith RSJ Frackowiak (1995) ArticleTitleStatistical parametric maps in functional imaging. A general linear approach Hum Brain Mapp 2 189–210 Occurrence Handle10.1002/hbm.460020402

    Article  Google Scholar 

  8. MF Folstein SE Folstein PR McHugh (1975) ArticleTitleMini mental state: a practical method for grading the cognitive state of patients for clinicians J Psychiatr Res 12 189–98 Occurrence Handle1202204 Occurrence Handle10.1016/0022-3956(75)90026-6 Occurrence Handle1:STN:280:CSmD2s7mtVE%3D

    Article  PubMed  CAS  Google Scholar 

  9. WG Rosen RC Mohs KL Davis (1984) ArticleTitleA new rating scale for Alzheimer's disease Am J Psychiatr 141 1356–64 Occurrence Handle6496779 Occurrence Handle1:STN:280:BiqD2cvjvFI%3D

    PubMed  CAS  Google Scholar 

  10. G McKhann D Drachman M Folstein R Katzman D Price EM Stadlan (1984) ArticleTitleClinical 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 Occurrence Handle6610841 Occurrence Handle1:STN:280:BiuB2cnis1M%3D

    PubMed  CAS  Google Scholar 

  11. American Psychiatric Association. Quick reference to the diagnostic criteria from DSM-4. American Psychiatric Association, 1994

  12. The World Health Organization. The ICD-10 classification of mental and behavioral disorders diagnostic criteria for research. World Health Organization, 1993

  13. JT Moroney E Bagiella DW Desmond VC Hachinski PK Molsa L Gustafson et al. (1997) ArticleTitleMeta-analysis of the Hachinski's ischemic score in pathologically verified dementias Neurology 49 1096–105 Occurrence Handle9339696 Occurrence Handle1:STN:280:ByiH2sbmtFE%3D

    PubMed  CAS  Google Scholar 

  14. CP Hughes L Berg WL Danziger LA Coben RL Martin (1982) ArticleTitleA new clinical scale for the staging of dementia Br J Psychiatr 140 566–72 Occurrence Handle1:STN:280:Bi2B2MjpsFI%3D Occurrence Handle10.1192/bjp.140.6.566

    Article  CAS  Google Scholar 

  15. A Homma M Takeda Y Imai F Udaka K Hasegawa M Kameyama et al. (2000) ArticleTitleClinical efficacy and safety of donepezil on cognitive and global function in patients with Alzheimer's disease Dement Geriatr Cogn Disord 11 299–313 Occurrence Handle11044775 Occurrence Handle10.1159/000017259 Occurrence Handle1:CAS:528:DC%2BD3cXotlyrurs%3D

    Article  PubMed  CAS  Google Scholar 

  16. SL Rogers LT Friedhoff (1998) ArticleTitleLong-term efficacy and safety of donepezil in the treatment of Alzheimer's disease, an interim analysis of the results of a US multicentre open label extension study Eur Neuropsychopharmacol 8 67–75 Occurrence Handle9452942 Occurrence Handle10.1016/S0924-977X(97)00079-5 Occurrence Handle1:CAS:528:DyaK1cXmtVemug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  17. SL Rogers RS Doody RD Pratt JR Ieni (2000) ArticleTitleLong-term efficacy and safety of donepezil in the treatment of Alzheimer's disease, final analysis of a US multicentre open-label study Eur Neuropsychopharmacol 10 195–203 Occurrence Handle10793322 Occurrence Handle10.1016/S0924-977X(00)00067-5 Occurrence Handle1:CAS:528:DC%2BD3cXivVGgtro%3D

    Article  PubMed  CAS  Google Scholar 

  18. HP Matthews J Korbey DG Wilkinson J Rowden (2000) ArticleTitleDonepezil in Alzheimer's disease, eighteen month results from Southampton memory clinic Int J Geriatr Psychiatry 15 713–20 Occurrence Handle10960883 Occurrence Handle10.1002/1099-1166(200008)15:8<713::AID-GPS187>3.0.CO;2-I Occurrence Handle1:STN:280:DC%2BD3cvotFGktQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  19. M Evans A Ellis D Watson T Chowdhury (2000) ArticleTitleSustained cognitive improvement following treatment of Alzheimer's disease with donepezil Int J Geriatr Psychiatry 15 50–3 Occurrence Handle10637404 Occurrence Handle10.1002/(SICI)1099-1166(200001)15:1<50::AID-GPS75>3.0.CO;2-M Occurrence Handle1:STN:280:DC%2BD3c7gsFKrsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  20. B Zikopoulos H Barbas (2006) ArticleTitlePrefrontal projections to the thalamic reticular nucleus form a unique circuit for attentional mechanisms J Neurosci 26 7348–61 Occurrence Handle16837581 Occurrence Handle10.1523/JNEUROSCI.5511-05.2006 Occurrence Handle1:CAS:528:DC%2BD28XnsVWntLs%3D

    Article  PubMed  CAS  Google Scholar 

  21. JC Culham KF Valyear (2006) ArticleTitleHuman parietal cortex in action Curr Opin Neurobiol 16 205–12 Occurrence Handle16563735 Occurrence Handle10.1016/j.conb.2006.03.005 Occurrence Handle1:CAS:528:DC%2BD28Xjs1Gku74%3D

    Article  PubMed  CAS  Google Scholar 

  22. Stahl SM. Essential psychopharmacology: neuroscientific basis and practical applications. 2nd ed. American Psychiatric Association; 2000. p. 448–85

  23. JL Cummings M Mega K Gray S Rosenberg-Thompson DA Carusi J Gornbein (1994) ArticleTitleThe Neuropsychiatric inventry: comprehensive assessment of psychopathology in dementia Neurology 44 2308–14 Occurrence Handle7991117 Occurrence Handle1:STN:280:ByqD1czhtFU%3D

    PubMed  CAS  Google Scholar 

  24. F Nobili M Koulibaly P Vitali O Migneco G Mariani K Ebmeier et al. (2002) ArticleTitleBrain perfusion follow-up in Alzheimer's patients during treatment with acetylcholinesterase inhibitors J Nucl Med 43 983–90 Occurrence Handle12163621 Occurrence Handle1:CAS:528:DC%2BD38Xms1Shurc%3D

    PubMed  CAS  Google Scholar 

  25. S Shimizu H Hanyu T Iwamoto K Koizumi K Abe (2006) ArticleTitleSPECT follow-up study of cerebral blood flow changes during Donepezil therapy in patients with Alzheimer's disease J Neuroimaging 16 16–23 Occurrence Handle16483272

    PubMed  Google Scholar 

  26. F Nobili P Vitali M Canfora N Girtler C De Leo G Mariani et al. (2002) ArticleTitleEffects of long-term Donepezil therapy on rCBF of Alzheimer's patients Clin Neurophysiol 113 1241–8 Occurrence Handle12140003 Occurrence Handle10.1016/S1388-2457(02)00110-4 Occurrence Handle1:CAS:528:DC%2BD38XntVGrt7c%3D

    Article  PubMed  CAS  Google Scholar 

  27. S Nakano T Asada H Matsuda M Uno M Takasaki (2001) ArticleTitleDonepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease J Nucl Med 42 1441–5 Occurrence Handle11585854 Occurrence Handle1:CAS:528:DC%2BD38XksVSmtbc%3D

    PubMed  CAS  Google Scholar 

  28. R Ceravolo D Volterrani G Tognoni G Dell'Agnello G Manca L Kiferle et al. (2004) ArticleTitleCerebral perfusional effects of cholinesterase inhibitors in Alzheimer's disease Clin Neuropharmacol 27 166–70 Occurrence Handle15319702 Occurrence Handle10.1097/01.wnf.0000138636.42121.45 Occurrence Handle1:CAS:528:DC%2BD2cXmvVars78%3D

    Article  PubMed  CAS  Google Scholar 

  29. H Hanyu T Shimizu Y Tanaka M Takasaki K Koizumi K Abe (2003) ArticleTitleRegional cerebral blood flow patterns and response to donepezil treatment in patients with Alzheimer's disease Dement Geriat Cogn Disord 15 177–82 Occurrence Handle10.1159/000068785 Occurrence Handle1:CAS:528:DC%2BD3sXitVSjsL8%3D

    Article  CAS  Google Scholar 

  30. RT Staff HG Gemmell MF Shanks AD Murray A Venneri (2000) ArticleTitleChanges in the rCBF images of patients with Alzheimer's disease receiving Donepezil therapy Nucl Mes Commun 21 37–41 Occurrence Handle10.1097/00006231-200001000-00007 Occurrence Handle1:CAS:528:DC%2BD3cXhtlGmsrw%3D

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tsunetaka Yoshida.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoshida, T., Ha-Kawa, S., Yoshimura, M. et al. Effectiveness of treatment with donepezil hydrochloride and changes in regional cerebral blood flow in patients with Alzheimer's disease. Ann Nucl Med 21, 257–265 (2007). https://doi.org/10.1007/s12149-007-0022-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12149-007-0022-2

Key words

Navigation