Summary.
In this study 11 patients with mild Alzheimer’s disease (AD) were treated with the cholinesterase inhibitor rivastigmine (mean dose 8.6 ± 1.3’mg) for 12 months and underwent positron emission tomography (PET) studies of cerebral glucose metabolism (CMRglc) and neuropsychological testing at baseline and after 12 months. An untreated group of 10 AD patients served as control group. While the untreated AD patients showed a significant decline of CMRglc in the temporo-parietal and frontal cortical regions after 12 months follow-up the rivastigmine-treated patients showed no decline in CMRglc in corresponding cortical brain regions. Furthermore, a significant dose-related increase in CMRglc was recorded in the right frontal association region after 12 months rivastigmine treatment. A positive correlation was observed between changes in CMRglc and several cognitive tests in patients receiving higher doses (10.5–12’mg) of rivastigmine. These results suggest a stabilization effect of rivastigmine on CMRglc in mild AD patients receiving long-term rivastigmine treatment.
Similar content being viewed by others
References
GE Alexander K Chen P Pietrini SI Rapoport EM Reiman (2002) ArticleTitleLongitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer’s disease treatment studies. Am J Psychiatry 159 738–745 Occurrence Handle10.1176/appi.ajp.159.5.738 Occurrence Handle11986126
MT Alkire RJ Haier SJ Barker NK Shah JC Wu YJ Kao (1995) ArticleTitleCerebral metabolism during propofol anesthesia in humans studied with positron emission tomography. Anesthesiology 82 393–403 Occurrence Handle1:CAS:528:DyaK2MXksFantrk%3D Occurrence Handle7856898
O Almkvist T Darreh-Shori E Stefanova R Spiegel A Nordberg (2004) ArticleTitlePreserved cognitive function after 12 months of treatment with rivastigmine in mild Alzheimer’s disease in comparison with untreated AD and MCI patients. Eur J Neurol 11 253–261 Occurrence Handle10.1046/j.1468-1331.2003.00757.x Occurrence Handle1:STN:280:DC%2BD2c7mvFSlsg%3D%3D Occurrence Handle15061827
JL Andersson (1997) ArticleTitleHow to estimate global activity independent of changes in local activity. Neuroimage 6 237–244 Occurrence Handle10.1006/nimg.1997.0302 Occurrence Handle1:STN:280:DyaK1c7hs12rsA%3D%3D Occurrence Handle9453855
JL Andersson L Thurfjell (1997) ArticleTitleImplementation and validation of a fully automatic system for intra- and interindividual registration of PET brain scans. J Comput Assist Tomogr 21 136–144 Occurrence Handle10.1097/00004728-199701000-00027 Occurrence Handle1:STN:280:ByiC2srht1I%3D Occurrence Handle9022786
L Bäckman Y Forsell (1994) ArticleTitleEpisodic memory functioning in a community-based sample of old adults with major depression: utilization of cognitive support. J Abnorm Psychol 103 361–370 Occurrence Handle8040505
R Cabeza ND Anderson S Houle JA Mangels L Nyberg (2000) ArticleTitleAge-related differences in neural activity during item and temporal-order memory retrieval: a positron emission tomography study. J Cogn Neurosci 12 197–206 Occurrence Handle1:STN:280:DC%2BD3c3jtl2rsg%3D%3D Occurrence Handle10769316
T Darreh-Shori O Almkvist ZZ Guan A Garlind B Strandberg AL Svensson H Soreq E Hellström-Lindahl A Nordberg (2002) ArticleTitleSustained cholinesterase inhibition in AD patients receiving rivastigmine for 12 months. Neurology 59 563–572 Occurrence Handle1:CAS:528:DC%2BD38XntlSrtr4%3D Occurrence Handle12196650
RS Doody JC Stevens C Beck RM Dubinsky JA Kaye L Gwyther RC Mohs LJ Thal PJ Whitehouse ST DeKosky JL Cummings (2001) ArticleTitlePractice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56 1154–1166 Occurrence Handle1:STN:280:DC%2BD3MzntFantw%3D%3D Occurrence Handle11342679
H Engler PO Lundberg K Ekbom I Nennesmo A Nilsson M Bergström H Tsukada P Hartvig B Langström (2003) ArticleTitleMultitracer study with positron emission tomography in Creutzfeldt-Jakob disease. Eur J Nucl Med Mol Imaging 30 85–95 Occurrence Handle1:CAS:528:DC%2BD38XpsV2iu7o%3D Occurrence Handle12483414
M Farlow R Anand J Messina SuffixJr R Hartman J Veach (2000) ArticleTitleA 52-week study of the efficacy of rivastigmine in patients with mild to moderately severe Alzheimer’s disease. Eur Neurol 44 236–241 Occurrence Handle10.1159/000008243 Occurrence Handle1:CAS:528:DC%2BD3cXovVeksrY%3D Occurrence Handle11096224
MF Folstein SE Folstein PR McHugh (1975) ArticleTitle“Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12 189–198 Occurrence Handle10.1016/0022-3956(75)90026-6 Occurrence Handle1:STN:280:CSmD2s7mtVE%3D Occurrence Handle1202204
K Friston A Holmes K Worsley J Poline C Frith R Frackowiak (1997) ArticleTitleStatistical parameteric maps in functional imaging: a general linear approach. Hum Brain Mapping 2 189–210
KJ Friston CD Frith PF Liddle RS Frackowiak (1991) ArticleTitleComparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 11 690–699 Occurrence Handle1:STN:280:By6B28fhslw%3D Occurrence Handle2050758
A Gjedde K Wienhard WD Heiss G Kloster NH Diemer K Herholz G Pawlik (1985) ArticleTitleComparative regional analysis of 2-fluorodeoxyglucose and methylglucose uptake in brain of four stroke patients. With special reference to the regional estimation of the lumped constant. J Cereb Blood Flow Metab 5 163–178 Occurrence Handle1:STN:280:BiqC1c3ptVQ%3D Occurrence Handle3872872
CL Grady JV Haxby NL Schlageter G Berg SI Rapoport (1986) ArticleTitleStability of metabolic and neuropsychological asymmetries in dementia of the Alzheimer type. Neurology 36 1390–1392 Occurrence Handle1:STN:280:BiiD3MrivVc%3D Occurrence Handle3762951
T Greitz C Bohm S Holte L Eriksson (1991) ArticleTitleA computerized brain atlas: construction anatomical content and some applications. J Comput Assist Tomogr 15 26–38 Occurrence Handle1:STN:280:By6C3c%2FltlA%3D Occurrence Handle1987199
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 Geriatr Cogn Disord 15 177–182 Occurrence Handle10.1159/000068785 Occurrence Handle1:CAS:528:DC%2BD3sXitVSjsL8%3D Occurrence Handle12626849
K Herholz R Adams J Kessler B Szelies M Grond W Heiss (1990) ArticleTitleCriteria for the diagnosis of Alzheimer’s disease with Positron Emission Tomography. Dementia 1 156–164
K Herholz A Nordberg E Salmon D Perani J Kessler R Mielke M Halber V Jelic O Almkvist F Collette M Alberoni A Kennedy S Hasselbalch F Fazio WD Heiss (1999) ArticleTitleImpairment of neocortical metabolism predicts progression in Alzheimer’s disease. Dement Geriatr Cogn Disord 10 494–504 Occurrence Handle10.1159/000017196 Occurrence Handle1:CAS:528:DC%2BD3cXjtFGh Occurrence Handle10559566
R Hunter DJ Wyper J Patterson MT Hansen GM Goodwin (1991) ArticleTitleCerebral pharmacodynamics of physostigmine in Alzheimer’s disease investigated using single-photon computerised tomography. Br J Psychiatry 158 351–357 Occurrence Handle1:STN:280:By6B2c3psFY%3D Occurrence Handle2036533
Y Karaman F Erdogan E Koseoglu T Turan AO Ersoy (2005) ArticleTitleA 12-month study of the efficacy of rivastigmine in patients with advanced moderate Alzheimer’s disease. Dement Geriatr Cogn Disord 19 51–56 Occurrence Handle10.1159/000080972 Occurrence Handle1:CAS:528:DC%2BD2cXhtVOjs7nL Occurrence Handle15383747
Lezak M (1995) Neuropsychological assessment, 3rd edn. Oxford University Press, New York
Luria A (1966) Higher cortical functions in man. Basic Books, New York
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 34 939–944 Occurrence Handle1:STN:280:BiuB2cnis1M%3D Occurrence Handle6610841
MS Mega JL Cummings SM O’Connor ID Dinov E Reback J Felix DL Masterman ME Phelps GW Small AW Toga (2001) ArticleTitleCognitive and metabolic responses to metrifonate therapy in Alzheimer disease. Neuropsychiatry Neuropsychol Behav Neurol 14 63–68 Occurrence Handle1:STN:280:DC%2BD3M3lvVKhsA%3D%3D Occurrence Handle11234910
MS Mega ID Dinov L Lee SM O’Connor DM Masterman B Wilen F Mishkin AW Toga JL Cummings (2000) ArticleTitleOrbital and dorsolateral frontal perfusion defect associated with behavioral response to cholinesterase inhibitor therapy in Alzheimer’s disease. J Neuro psychiatr Clin Neurosci 12 209–218 Occurrence Handle1:CAS:528:DC%2BD3MXitlKgtbw%3D
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 1441–1445 Occurrence Handle1:CAS:528:DC%2BD38XksVSmtbc%3D Occurrence Handle11585854
T Nariai JJ DeGeorge Y Lamour SI Rapoport (1991) ArticleTitleIn vivo brain incorporation of [1–14C] arachidonate in awake rats, with or without cholinergic stimulation, following unilateral lesioning of nucleus basalis magnocellularis. Brain Res 559 1–9 Occurrence Handle10.1016/0006-8993(91)90279-5 Occurrence Handle1:CAS:528:DyaK3MXlvF2msLg%3D Occurrence Handle1723641
F Nobili M Koulibaly P Vitali O Migneco G Mariani K Ebmeier A Pupi PH Robert G Rodriguez J Darcourt (2002a) ArticleTitleBrain perfusion follow-up in Alzheimer’s patients during treatment with acetylcholinesterase inhibitors. J Nucl Med 43 983–990 Occurrence Handle1:CAS:528:DC%2BD38Xms1Shurc%3D
F Nobili P Vitali M Canfora N Girtler C De Leo G Mariani A Pupi G Rodriguez (2002b) ArticleTitleEffects of long-term Donepezil therapy on rCBF of Alzheimer’s patients. Clin Neurophysiol 113 1241–1248 Occurrence Handle10.1016/S1388-2457(02)00110-4 Occurrence Handle1:CAS:528:DC%2BD38XntVGrt7c%3D
Nordberg A (2000) The effect of cholinesterase inhibitors studied with brain imaging. In: Giacobini E (ed) Cholinesterases and cholinesterase inhibitors. Martin Dunitz, London, pp 237–247
CS Patlak RG Blasberg JD Fenstermacher (1983) ArticleTitleGraphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3 1–7 Occurrence Handle1:STN:280:BiyC3cbjtlI%3D Occurrence Handle6822610
SG Potkin R Anand K Fleming G Alva D Keator D Carreon J Messina JC Wu R Hartman JH Fallon (2001) ArticleTitleBrain metabolic and clinical effects of rivastigmine in Alzheimer’s disease. Int J Neuropsychopharmacol 4 223–230 Occurrence Handle10.1017/S1461145701002528 Occurrence Handle1:CAS:528:DC%2BD3MXnvVCktb0%3D Occurrence Handle11602028
G Rodriguez P Vitali M Canfora P Calvini N Girtler C De Leo A Piccardo F Nobili (2004) ArticleTitleQuantitative EEG and perfusional single photon emission computed tomography correlation during long-term donepezil therapy in Alzheimer’s disease. Clin Neurophysiol 115 39–49 Occurrence Handle10.1016/S1388-2457(03)00321-3 Occurrence Handle1:CAS:528:DC%2BD2cXptlWi Occurrence Handle14706467
SA Rombouts F Barkhof CS Van Meel P Scheltens (2002) ArticleTitleAlterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 73 665–671 Occurrence Handle10.1136/jnnp.73.6.665 Occurrence Handle1:STN:280:DC%2BD38nnvVGktw%3D%3D Occurrence Handle12438467
M Signorini E Paulesu K Friston D Perani A Colleluori G Lucignani F Grassi V Bettinardi RS Frackowiak F Fazio (1999) ArticleTitleRapid assessment of regional cerebral metabolic abnormalities in single subjects with quantitative and nonquantitative [18F]FDG PET: a clinical validation of statistical parametric mapping. Neuroimage 9 63–80 Occurrence Handle10.1006/nimg.1998.0381 Occurrence Handle1:STN:280:DyaK1M7hvFGisg%3D%3D Occurrence Handle9918728
Talairach J, Tournoux P (1988) A co-planar stereotactic atlas of the human brain. G Thieme, Stuttgart
L Thurfjell C Bohm E Bengtsson (1995) ArticleTitleCBA – an atlas-based software tool used to facilitate the interpretation of neuroimaging data. Comput Methods Programs Biomed 47 51–71 Occurrence Handle10.1016/0169-2607(95)01629-8 Occurrence Handle1:STN:280:BymD2MzptVQ%3D Occurrence Handle7554863
L Tune PJ Tiseo J Ieni C Perdomo RD Pratt JR Votaw RD Jewart JM Hoffman (2003) ArticleTitleDonepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24-week, double-blind, placebo-controlled study. Am J Geriatr Psychiatry 11 169–177 Occurrence Handle12611746
Wechsler D (1981) Wechsler Adult Intelligence Scale, revised: Manual. Psychological Corporation, New York
A Vennerica MF Shanks RT Staff SJ Pestell KE Forbes HG Gemmell AD Murray (2002) ArticleTitleCerebral blood flow and cognitive responses to rivastigmine treatment in Alzheimer’s disease. Neuroreport 13 83–87 Occurrence Handle11924899
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Stefanova, E., Wall, A., Almkvist, O. et al. Longitudinal PET evaluation of cerebral glucose metabolism in rivastigmine treated patients with mild Alzheimer’s disease. J Neural Transm 113, 205–218 (2006). https://doi.org/10.1007/s00702-005-0312-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-005-0312-6