Summary
Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxis, and executive functions. The rCBF measured by99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N=12) and AD2 (N=23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.
Similar content being viewed by others
References
Albert MS, Duffy FH, McAnulty GB (1990) Electrophysiologic comparisons between two groups of patients with Alzheimer's disease. Arch Neurol 47: 857–863
Borkowski JG, Benton AL, Spreen O (1967) Word fluency and brain damage. Neuropsychologia 5: 135–140
Burns A, Philpot M, Costa D, Ell P, Levy R (1989) The investigation of Alzheimer's disease with single photon emission tomography. J Neurol Neurosurg Psychiatry 52: 248–253
Byrne EJ, Arie T (1994) Tetrahydroaminoacridine and Alzheimer's disease. For the few, but we don't know which few. BMJ 308: 868–869
Chui HC, Teng EL, Henderson VW, Moy AC (1985) Clinical subtypes of dementia of the Alzheimer type. Neurology 35: 1544–1550
Drachman DA, O'Donnell BF, Lew RA, Swearer JM (1990) The prognosis of Alzheimer's disease ‘How far’ rather than ‘how fast’ best predicts the course. Arch Neurol 47: 851–856
Eagger SA, Levy R, Sahakian BJ (1991) Tacrine in Alzheimer's disease. Lancet 337: 989–992
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-Mental State”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatry Res 12: 189–198
Friedland RP, Budinger TF, Ganz E, Yano Y, Mathis CA, Koss B, Ober BA, Huesman RH, Derenzo SE (1983) Regional metabolic alterations in dementia of the Alzheimer type: positron emission tomography with [18F]fluorodeoxyglucose. J Comput Assist Tomogr 7: 590–598
Frlich L, Eilles C, Ihl R, Maurer K, Lancjik M (1989) Stage-dependent reductions of regional cerebral blood flow measured by HMPAO-SPECT in dementia of Alzheimer type. Psychiatry Res 29: 347–350
Geaney DP, Soper N, Shepstone BJ, Cowen PJ (1990) Effect of central cholinergic stimulation on regional cerebral blood flow in Alzheimer's disease. Lancet 335: 1484–1487
Gemmell H, Sharp O, Besson J (1987) Differential diagnosis of dementia using the cerebral blood flow agent99mTC HMPAO: a SPECT study. J Comput Assist Tomogr 11: 398–402
Goodglass H, Kaplan E (1972) The assessment of aphasia and related disorders. Lea and Febiger, Philadelphia
Habert MO, Spampinato U, Mas JL, Piketty ML, Bourdel MC, de Recordo J, Rondot P, Askienazy S (1991) A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia. Eur J Nucl Med 18: 3–11
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56–62
Helkala E-L, Laulumaa V, Soininen H, Riekkinen PJ (1988) Recall and recognition memory in patients with Alzheimer's and Parkinson's diseases. Ann Neurol 24: 214–217
Helkala EL, Laulumaa V, Soininen H, Partanen J, Riekkinen PJ (1991) Different patterns of cognitive decline related to normal and deteriorating EEG in three year follow-up study of patients with Alzheimer's disease. Neurology 41: 528–532
Hunter R, McLuskie R, Wyper D, Patterson J, Christie JE, Brooks DN, McCullock J, Fink G, Goodwin GM (1989) The pattern of function-related regional cerebral blood flow investigated by single photon emission tomography with99mTc-HMPAO in patients with presenile Alzheimer's disease and Korsakoff's psychosis. Psychol Med 19: 847–855
Jagust WJ, Reed BR, Seab JP, Budinger TF (1990) Alzheimer's disease. Age at onset and single-photon emission computed tomographic patterns of regional cerebral blood flow. Arch Neurol 47: 628–633
Kaplan E, Goodglass H, Weintraub S (1983) The Boston naming test. Lea and Febiger, Philadephia
Knesevich JW, Toro FR, Morris JC, LaBarge E (1985) Afasia, family history, and longitudinal course of senile dementia of the Alzheimer type. Psychiatry Res 14: 255–263
Kuikka J, Tenhunen-Eskelinen M, Jurvelin J, Kiiliänen H (1993) Physical performance of the Siemens MultiSPECT 3 gamma camera. Nucl Med Commun 14: 490–497
Martin A, Brouwers P, Lalonde F, Cox C, Teleska P, Fedio P (1986) Towards behavioral typology of Alzheimer's patients. J Clin Exp Neuropsychol 8: 594–610
Mayeux R, Stern Y, Spanton S (1985) Heterogeneity in dementia of the Alzheimer type: evidence of subgroups. Neurology 35: 453–461
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: 939–944
Mesulam MM (1981) A cortical network for directed attention and unilateral neglect. Ann Neurol 10: 309–325
Neary D, Snowden JS, Shields RA, Shields RS, Burjan AWI, Northen B, MacDermott N, Prescott MC, Testa HJ (1987) Single photon emission tomography using99mTc-HM-PAO in the investigation dementia. J Neurol Neurosurg Psychiatry 50: 1101–1109
Nelson HE (1976) A modified card sorting test sensitive to frontal lobe defects. Cortex 12: 313–324
O'Brien JT, Eagger S, Syed GMS, Sahakian BJ, Levy R (1992) A study of regional cerebral blood flow and cognitive performance in Alzheimer's disease. J Neurol Neurosurg Psychiatry 55: 1182–1187
Perani D, Di Piero V, Vallar G, Cappa S, Messa C, Bottini G, Berti A, Passafiume D, Scarlato G, Gerundini P, Lenzi GL, Fazio F (1988) Technetium-99m HM-PAO-SPECT study of regional cerebral perfusion in early Alzheimer's disease. J Nucl Med 29: 1507–1514
Reisberg B, Schneck MK, Ferris SH (1983) The brief cognitive rating scale (BCRS): findings in primary degenerative dementia (PDD). Psychopharmacol Bull 19: 734–739
Reitan RM (1958) Validity of the Trail Making test as an indicator of organic brain damage. Percept Mot Skills 8: 271–276
Rosen WG, Terry RD, Fuld PA, Katzman R, Beck A (1980) Pathological verification of ischemic score in differentiation of dementias. Ann Neurol 17: 486–488
Rossor M, Iversen L, Reynolds G (1984) Neurochemical characteritics of early and late onset types of Alzheimer's disease. BMJ 288: 961–964
Rossor MN (1993) Molecular pathology of Alzheimer's disease. J Neurol Neurosurg Psychiatry 56: 583–586
Russell EW (1975) A multiple scoring method for the assessment of complex memory functions. J Cons Clin Psychol 43: 800–809
Soininen H, Helkala EL, Laulumaa V, Soikkeli R, Hartikainen P, Riekkinen PJ (1992a) Cognitive profile of Alzheimer patients with extrapyramidal signs: a longitudinal study. J Neural Transm [P-D Sect] 4: 241–254
Soininen H, Laulumaa V, Helkala EL, Hartikainen P, Riekkinen PJ (1992b) Extrapyramidal signs in Alzheimer's disease: a 3-year follow-up study. J Neural Transm [P-D Sect] 4: 107–119
Stern Y, Hesdorffer D, Sano M, Mayeux R (1990) Measurement and prediction of functional capacity in Alzheimer's disease. Neurology 40: 8–14
Webster DD (1968) Clinical analysis of the disability on Parkinson's disease. Mod Treat 5: 257–262
Wechsler D (1945) A standardised memory scale for clinical use. J Psychol 19: 87–95
Wechsler D (1981) WAIS-R Manual. Psychological Corporation, New York
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Soininen, H., Helkala, E.L., Kuikka, J. et al. Regional cerebral blood flow measured by99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease. J Neural Transm Gen Sect 9, 95–109 (1995). https://doi.org/10.1007/BF02259652
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02259652