Skip to main content
SpringerLink
Log in

A Meta-Analysis of Structural and Functional Brain Imaging in Dementia of the Alzheimer's Type: A Neuroimaging Profile

  • Published:
Neuropsychology Review Aims and scope Submit manuscript

Abstract

We conducted a quantitative review of the imaging literature using meta-analytic methodology to characterize further the magnitude of hippocampal deficit in probable Alzheimer's disease (AD) and to determine whether other neuroanatomic structures in AD can better discriminate the disease from normal aging. Additionally, we parceled the discriminability of neuroanatomic structures by duration of disease to determine those structures most sensitive to AD in its early and late stages. One hundred twenty-one studies published between 1984 and 2000 met criteria for inclusion in the present analysis. In total, structural (i.e., CT and MRI) and functional (i.e., SPECT and PET) neuroimaging results from 3511 patients with AD, and 1632 normal healthy controls were recorded across meta-analyses. Our results include neuroimaging profiles for both early onset and longer duration patients with AD. In sum, these profiles yield a signature of diagnostic markers in both cortical and subcortical neuroanatomic areas. This signature is consistent with the clinical phenomenology of Alzheimer's dementia and should aid in the positive identification of AD.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Similar content being viewed by others

REFERENCES

  • Akiyama, H., Harrop, R., McGeer, P. L., Peppard, R., and McGeer, E. G. (1989). Crossed cerebellar and uncrossed basal ganglia and thalamic diaschisis in Alzheimer's disease. Neurology 39: 541–548.

    Google Scholar 

  • Alavi, A., Newberg, A. B., Souder, E., and Berlin, J. A. (1993). Quantitative analysis of PET and MRI data in normal aging and Alzheimer's disease: Atrophy weighted total brain metabolism and absolute whole brain metabolism as reliable discriminators. J. Nucl. Med. 34: 1681–1687.

    Google Scholar 

  • Azari, N. P., Pettigrew, K. D., Schapiro, M. B., Haxby, J. V., Grady, C. L., Pietrini, P., et al. (1993). Early detection of Alzheimer's disease: Astatistical approach using positron emission tomographic data. J. Cereb. Blood Flow Metab. 13: 438–447.

    Google Scholar 

  • Baron, J. C., Chetelat, G., Desgranges, B., Perchey, G., Landeau, B., de la Sayette, V., et al. (2001). In vivo mapping of gray matter loss with voxel based morphometry in mild Alzheimer's disease. Neuroimage 14: 298–309.

    Google Scholar 

  • Barta, P. E., Powers, R. E., Aylward, E. H., Chase, G. A., Harris, G. J., Rabins, P. V., et al. (1997). Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls. Psychiatry Res. 68: 65–75.

    Google Scholar 

  • Bartzokis, G., Sultzer, D., Mintz, J., Holt, L. E., Marx, P., Phelan, C. K., et al. (1994). In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI. Biol. Psychiatry 35: 480–487.

    Google Scholar 

  • Beasley, C. M., Nilsson, M. E., Koke, S. C., and Gonzales, J. S. (2000). Efficacy, adverse events, and treatment discontinuations in fluox-etine clinical studies of major depression: A meta-analysis of the 20-mg/day dose. J. Clin. Psychiatry 61: 722–728.

    Google Scholar 

  • Besson, J. A. O., Crawford, J. R., Parker, D. M., and Smith, F. W. (1989). Magnetic resonance imaging in Alzheimer's disease, multi-infarct dementia, alcoholic dementia and Korsakoff's psychosis. Acta Psychiatr. Scand. 80: 451–458.

    Google Scholar 

  • Biegon, A., Eberling, J. L., Richardson, B. C., Roos, M. S., Wong, S. T. S., Reed, B. R., et al. (1994). Human corpus callosum in aging and Alzheimer's disease: A magnetic resonance imaging study. Neurobiol. Aging 15: 393–397.

    Google Scholar 

  • Blin, J., Piercey, M., Giuffra, M. E., Mouradian, M. M., and Chase, T. N. (1994). Metabolic effects of scopolamine and physostigmine in human brain measured by positron emission tomography. J. Neu-rol. Sci. 123: 44–51.

    Google Scholar 

  • Bondi, M. W., and Monsch, A. U. (1998). The role of memory assessment in the preclinical detection of dementia. In: Troster, A. I. (ed.), Memory in Neurodegenerative Disease: Biological, Cognitive, and Clinical Perspectives, Cambridge University Press, Cambridge, MA, pp. 278–289.

    Google Scholar 

  • Braak, H., and Braak, E. (1991). Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. (Berl.) 82: 239–259.

    Google Scholar 

  • Braak, H., and Braak, E. (1997). Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol. Aging 18: 351–357.

    Google Scholar 

  • Braak, E., Griffing, K., Arai, K., Bohl, J., Bratzke, H., and Braak, H. (1999). Neuropathology of Alzheimer's disease: What is new since A.Alzheimer? Eur. Arch. Psychiatry Clin. Neurosci. 249: S14-S22.

    Google Scholar 

  • Brown, G. G., Levine, S. R., Gorell, J. M., Pettegrew, J. W., Gdowski, J. W., Bueri, J. A., et al. (1989). In vivo 31 P NMR profiles of Alzheimer's disease and multiple subcortical infarct dementia. Neurology 39: 1423–1427.

    Google Scholar 

  • Buchpiguel, C. A., Alavi, J. B., Alavi, A., and Kenyon, L. C. (1995). PET versus SPECT in distinguishing radiation necrosis from tumor recurrence in the brain. J. Nucl. Med. 36: 159–164.

    Google Scholar 

  • Burns, A., Philpot, M. P., Costa, D. C., and Levy, R. (1989). The in-vestigation of Alzheimer's disease with single photon emission tomography. J. Neurol. Neurosurg. Psychiatry 52: 248–253.

    Google Scholar 

  • Burns, A., Jacoby, R., Philpot, M., and Levy, R. (1991). Computerised tomography in Alzheimer's disease: Methods of scan analysis, comparison with normal controls, and clinical/radiological associations. Br. J. Psychiatry 159: 609–614.

    Google Scholar 

  • Charletta, D. A., Bennett, D. A., and Wilson, R. S. (1993). Computed tomography and magnetic resonance imaging. In: Parks, R. W., Zec, R. F., and Wilson, R. S. (eds.), Neuropsychology of Alzheimer's Disease and Other Dementias, Oxford University Press, New York, pp. 534–564.

    Google Scholar 

  • Chawluk, J. B., Dann, R., Alavi, A., Hurtig, H. I., Gur, R. E., Resnick, S., et al. (1990). The effect of focal cerebral atrophy in positron emission tomographic studies of aging and dementia. Int. J. Radiat. Appl. Instr. 17: 797–804.

    Google Scholar 

  • Cohen, J. (1988). Statistical Power Analysis for the Behavioral Sciences (2nd Ed.), Erlbaum, Hillsdale, NJ.

    Google Scholar 

  • Cooper, H. (1979). Statistically combining independent studies: A meta-analysis of sex differences in conformity research. J. Pers. Soc. Psychol. 37: 131–146.

    Google Scholar 

  • Cooper, H., and Hedges, L. V. (1994). The Handbook of Research Synthesis, Russell Sage Foundation, New York.

    Google Scholar 

  • Costa, D. C., Ell, P. J., Philpot, M., and Levy, R. (1988). CBF tomograms with [99mTc-HM-PAO] in patients with dementia (Alzheimer type and HIV) and Parkinson's disease-Initial results. J. Cereb. Blood Flow Metab. 8: S109-S115.

    Google Scholar 

  • Cuénod, C.-A., Denys, A., Michot, J.-L., Jehenson, P., Forette, F., Kaplan, D., et al. (1993). Amygdala atrophy in Alzheimer's disease: An in vivo magnetic resonance imaging study. Arch. Neurol. 50: 941–945.

    Google Scholar 

  • Cummings, J. L., and Benson, D. F. (1992). Dementia: A Clinical Approach, Butterworth-Heinemann, Boston.

    Google Scholar 

  • Currant, S. M., Murray, C. M., Van Beck, M., Dougall, N., O'Carroll, R. E., Austin, M.-P., et al. (1993). A single photon emission computerized tomography study of regional brain function in elderly patients with major depression and with Alzheimer-type dementia. Br. J. Psychiatry 163: 155–165.

    Google Scholar 

  • Dalgalarrondo, F. H., Riecher-Rössler, A., Geiger-Kabisch, C., and Hentschel, F. (1994). Organic factors and the clinical features of late paranoid psychosis: A comparison with Alzheimer's disease and normal ageing. Acta Psychiatr. Scand. 89: 335–340.

    Google Scholar 

  • Damasio, H., and Damasio, A. R. (1989). Lesion Analysis in Neuropsychology, Oxford University Press, New York.

    Google Scholar 

  • DeCarli, C., Haxby, J. V., Gillette, J. A., Teichberg, D., Rapoport, S. I., and Schapiro, M. B. (1992). Longitudinal changes in lateral ven-tricular volume in patients with dementia of the Alzheimer type. Neurology 42: 2029–2036.

    Google Scholar 

  • DeCarli, C., Murphy, D. G. M., McIntosh, A. R., Teichberg, D., Schapiro, M. B., and Horwitz, B. (1995). Discriminant analysis of MRI measures as a method to determine the presence of dementia of the Alzheimer type. Psychiatry Res. 57: 119–130.

    Google Scholar 

  • DeCarli, C., Grady, C. L., Clark, C. M., Katz, D. A., Brady, D. R., Murphy, D. G. M., et al. (1996). Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter. J. Neurol. Neurosurg. Psychiatry 60: 158–167.

    Google Scholar 

  • De Leon, M. J., George, A. E., Reisberg, B., Kluger, A., Stylopoulos, L. A., Miller, J. D., et al. (1989). Alzheimer's disease: Longitudinal CT studies of ventricular change. Am. J. Roentgenol. 152: 1257–1262.

    Google Scholar 

  • De Leon, M. J., Convit, A., De Santi, S., Bobinski, M., George, A. E., Wisniewski, H. M., et al. (1997). Contribution of structural neu-roimaging to the early diagnosis of Alzheimer's disease. Int. Psy-chogeriatr. 9: 183–190.

    Google Scholar 

  • Deutsch, G., and Tweedy, J. R. (1987). Cerebral blood flow in severity-matched Alzheimer and multi-infarct patients. Neurology 37: 431–438.

    Google Scholar 

  • Duara, R., Barker, W. W., Chang, J., Yoshii, F., Loewenstein, D. A., and Pascal, S. (1992). Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease. J. Cereb. Blood Flow Metab. 12: 927–934.

    Google Scholar 

  • Erkinjuntti, T., Lee, D. H., Gao, F., Steenhuis, R., Eliasziw, M., Fry, R., et al. (1993). Temporal lobe atrophy on magnetic resonance imaging in the diagnosis of early Alzheimer's disease. Arch. Neurol. 50: 305–310.

    Google Scholar 

  • Fazekas, F., Alavi, A., Chawluk, J. B., Zimmerman, R. A., Hackney, D., Bilaniuk, L., et al. (1989). Comparison of CT, MR, and PET in Alzheimer's dementia and normal aging. J. Nucl. Med. 30: 1607–1615.

    Google Scholar 

  • Folstein, M. F., Folstein, S. E., and McHugh, P. R. (1975). Mini-mental state. J. Psychiatr. Res. 12: 189–198.

    Google Scholar 

  • Förstl, H., Burns, A., Jacoby, R., Eagger, S., and Levy, R. (1991a). Quantitative CT scan analysis in senile dementia of the Alzheimer type: II. Radioattenuation of grey and white matter. Int. J. Geriatr. Psychiatry 6: 715–719.

    Google Scholar 

  • Förstl, H., Burns, A., Jacoby, R., Eagger, S., and Levy, R. (1991b). Quantitative CT scan analysis in senile dementia of the Alzheimer type: I. Computerized planimetry of cerebrospinal fluid areas. Int. J. Geriatr. Psychiatry 6: 709–713.

    Google Scholar 

  • Fox, N. C., Crum, W. R., Scahill, R. I., Stevens, J. M., Janssen, J. C., and Rossor, M. N. (2001). Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images. Lancet 358: 201–205.

    Google Scholar 

  • Friedland, R. P., Jagust, W. J., Huesman, R. H., Koss, E., Knittel, B., Mathis, C. A., et al. (1989). Regional cerebral glucose transport and utilization in Alzheimer's disease. Neurology 39: 1427–1434.

    Google Scholar 

  • Frisoni, G. B., Beltramello, A., Geroldi, C., Weiss, C., Bianchetti, A., and Trabucchi, M. (1996). Brain atrophy in frontotemporal dementia. J. Neurol. Neurosurg. Psychiatry 61: 157–165.

    Google Scholar 

  • Frisoni, G. B., Laakso, M. P., Beltramello, A., Geroldi, C., Bianchetti, A., Soininen, H., et al. (1999). Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer's disease. Neurology 52: 91–100.

    Google Scholar 

  • Fukuyama, H., Ogawa, M., Yamauchi, H., Yamaguchi, S., Kimura, J., Yenokura, Y., et al. (1994). Altered cerebral energy metabolism in Alzheimer's disease: A PET study. J. Nucl. Med. 35: 1–6.

    Google Scholar 

  • Gloaguen, V., Cottraux, J., Cucherat, M., and Blackburn, I. M. (1998). A meta-analysis of the effects of cognitive therapy in depressed patients. J. Affect. Disord. 49: 59–72.

    Google Scholar 

  • Goto, I., Taniwaki, T., Hosokawa, S., Otsuka, M., Ichiya, Y., and Ichimiya, A. (1993). Positron emission tomographic (PET) studies in dementia. J. Neurol. Sci. 114: 1–6.

    Google Scholar 

  • Gould, R. A., Mueser, K. T., Bolton, E., Mays, V., and Goff, D. (2001). Cognitive therapy for psychosis in schizophrenia: An effect size analysis. Schizophr. Res. 48: 335–342.

    Google Scholar 

  • Grady, C. L., and Craik, F. I. (2000). Changes in memory processing with age. Curr. Opin. Neurobiol. 10: 224–231.

    Google Scholar 

  • Grady, C. L., Haxby, J. V., Horwitz, B., Gillette, J., Salerno, J. A., Gonzalez-Aviles, A., et al. (1993). Activation of cerebral blood flow during a visuoperceptual task in patients with Alzheimer-type dementia. Neurobiol. Aging 14: 35–44.

    Google Scholar 

  • Greene, J. D. W., Miles, K., and Hodges, J. R. (1996). Neuropsychology of memory and SPECT in the diagnosis and staging of dementia of Alzheimer type. J. Neurol. 243: 175–190.

    Google Scholar 

  • Grundman, M., Corey-Bloom, J., Jernigan, T., Archibald, S., and Thal, L. J. (1996). Low body weight in Alzheimer's disease is associated with mesial temporal cortex atrophy. Neurology 46: 1585–1591.

    Google Scholar 

  • Guze, B. H., Hofman, J. M., Maziotta, J. C., Baxter, L. R., Jr., and Phelps, M. E. (1992). Positron emission tomography and familial Alzheimer's disease: A pilot study. J. Am. Geriatr. Soc. 40: 120–123.

    Google Scholar 

  • Hampel, H., Teipel, S. J., Alexander, G. E., Horwitz, B., Teichberg, D., Schapiro, M. B., et al. (1998). Corpus callosum atrophy is a possible indicator of region-and cell type-specific neuronal degeneration in Alzheimer disease. Arch. Neurol. 55: 193–198.

    Google Scholar 

  • Harris, G. J., Lewis, R. F., Satlin, A., English, C. D., Scott, T. M., Yurgelun-Todd, D. A., et al. (1996). Dynamic susceptibility contrast MRI of regional blood volume in Alzheimer's disease. Am. J. Psychiatry 153: 721–724.

    Google Scholar 

  • Haxby, J. V., Grady, C. L., Koss, E., Horwitz, B., Schapiro, M., Friedland, R. P., et al. (1988). Heterogenous anterior-posterior metabolic patterns in dementia of the Alzheimer type. Neurology 38: 1853–1863.

    Google Scholar 

  • Haxby, J. V., Grady, C. L., Koss, E., Horwitz, B., Heston, L., Schapiro, M., et al. (1990). Longitudinal study of cerebral metabolic asymetries and associated neuropsychological patterns in early dementia of the Alzheimer type. Arch. Neurol. 47: 753–760.

    Google Scholar 

  • Hedges, L. V., and Olkin, I. (1985). Statistical Methods for Meta-Analysis, Academic Press, New York.

    Google Scholar 

  • Hellman, R. S., Tikofsky, R. S., Collier, B. D., Hoffmann, R. G., Palmer, D. W., Glatt, S. L., et al. (1989). Alzheimer disease: Quantitative analysis of I-123-iodoamphetamine SPECT brain imaging. Radiology 172: 183–188.

    Google Scholar 

  • Honig, L. S., and Mayeux, R. (2001). Natural history of Alzheimer's disease. Aging 13: 171–182.

    Google Scholar 

  • Hunter, J. E., and Schmidt, F. L. (1990). Methods of Meta-Analysis, Sage, Newbury Park, CA.

    Google Scholar 

  • Ishii, K., Imamura, T., Sasaki, M., Yamaji, S., Sakamoto, S., Kitagaki, H., et al. (1998). Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease. Neurology 51: 125–130.

    Google Scholar 

  • Jack, C. R., Petersen, R. C., Xu, Y. C., Waring, S. C., O'Brien, P. C., Tangalos, E. G., et al. (1997). Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease. Neurology 49: 786–794.

    Google Scholar 

  • Jack, C. R., Jr., Petersen, R. C., Xu, Y., O'Brien, P. C., Smith, G. E., Ivnik, R. J., et al. (1998). Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. Neurology 51: 993–999.

    Google Scholar 

  • Jagust, W. J., Johnson, K. A., and Holman, B. L. (1995). SPECT perfusion imaging in the diagnosis of dementia. J. Neuroimaging 5: S45-S52.

    Google Scholar 

  • Johnson, K. A., Homan, B. L., Mueller, S. P., Rosen, T. J., English, R., Nagel, J. S., et al. (1988). Single photon emission computed tomography in Alzheimer's disease: Abnormal iofetamine I 123 uptake reflects dementia severity. Arch. Neurol. 45: 392–396.

    Google Scholar 

  • Johnson, K. A., Holman, L., Rosen, T. J., Nagel, J. S., English, R. J., and Growdon, J. H. (1990). Iofetamine I 123 single photon emission computed tomography is accurate in the diagnosis of Alzheimer's disease. Arch. Intern. Med. 150: 752–756.

    Google Scholar 

  • Juottonen, K., Laakso, M. P., Partanen, K., and Soininen, H. (1999). Comparative MRanalysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease. Am. J. Neuroradiol. 20: 139–144.

    Google Scholar 

  • Karbe, H., Kertesz, A., Davis, J., Kemp, B. J., Prato, F. S., and Nicholson, R. L. (1994). Quantification of functional deficit in Alzheimer's disease using a computer-assisted mapping program for 99m Tc-HMPAO SPECT. Neuroradiology 36: 1–6.

    Google Scholar 

  • Kawabata, K., Tachibana, H., Sugita, M., and Fukuchi, M. (1993). A comparative I-123 SPECT study in Binswanger's disease and Alzheimer's disease. Clin. Nucl. Med. 18: 329–336.

    Google Scholar 

  • Kido, D. K., Caine, E. D., LeMay, M., Ekholm, S., Booth, H., and Panzer, R. (1989). Temporal lobe atrophy in patients with Alzheimer disease: A CT study. Am. J. Neuroradiol. 10: 551–555.

    Google Scholar 

  • Kidron, D., Black, S. E., Stanchev, P., Buck, B., Szalai, J. P., Parker, J., et al. (1997). Quantitative MR volumetry in Alzheimer's disease: Topographic markers and the effects of sex and education. Neurology 49: 1504–1512.

    Google Scholar 

  • Killiany, R. J., Moss, M. B., Albert, M. S., Sandor, T., Tieman, J., and Jolesz, F. (1993). Temporal lobe regions on magnetic reso-nance imaging identify patients with early Alzheimer's disease. Arch. Neurol. 50: 949–954.

    Google Scholar 

  • Koeppe, R. A., Mangner, T., Betz, A. L., Sulkin, B. L., Allen, R., Kollros, P., et al. (1990). Use of [11 C] aminocyclohexanecarboxy-late for the measurement of amino acid uptake and distribution volume in human brain. J. Cereb. Blood Flow Metab. 10: 727–739.

    Google Scholar 

  • Krasuski, J. S., Alexander, G. E., Horwitz, B., Daly, E. M., Murphy, D. G. M., Rapoport, S. I., et al. (1998). Volumes of medial temporal lobe structures in patients with Alzheimer's disease and mild cognitive impairment (and in healthy controls). Biol. Psychiatry 43: 60–68.

    Google Scholar 

  • Kumar, A., Schapiro, M. B., Grady, C., Haxby, J. V., Wagner, E., Salerno, J. A., et al. (1991). High-resolution PET studies in Alzheimer's disease. Neuropsychopharmacology 4: 35–46.

    Google Scholar 

  • Kuwabara, Y., Ichiya, Y., Otsuka, M., Masuda, K., Ichimiya, A., and Fujishima, M. (1992). Cerebrovascular responsiveness to hypercapnia in Alzheimer's dementia and vascular dementia of the Binswanger type. Stroke 23: 594–598.

    Google Scholar 

  • Laakso, M. P., Partanen, K., Riekkinen, P., Jr., Lehtovirta, M., Helkala, E.-L., Hallikainen, M., et al. (1996). Hippocampal volumes in Alzheimer's disease, Parkinson's disease with and without dementia, and in vascular dementia: An MRI study. Neurology 46: 678–681.

    Google Scholar 

  • Lachner, G., and Engel, R. R. (1994). Differentiation of dementia and depression by memory tests. A meta-analysis. J. Nerv. Ment. Dis. 182: 34–39.

    Google Scholar 

  • Lehéricy, S., Baulac, M., Chiras, J., Piérot, L., Martin, N., Pillon, B., et al. (1994). Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease. Am. J. Neuroradiol. 15: 927–937.

    Google Scholar 

  • Lehtovirta, M., Soininen, H., Laakso, M. P., Partanen, K., Helisalmi, S., Mannermaa, A., et al. (1996). SPECT and MRI analysis in Alzheimer's disease: Relation to apolipoprotein E 4 allele. J. Neu-rol. Neurosurg. Psychiatry 60: 644–649.

    Google Scholar 

  • Lehtovitra, M., Kuikka, J., Helisalmi, S., Hartikainen, P., Mannermaa, A., Ryynänen, M., et al. (1998). Longitudinal SPECT study in Alzheimer's disease: Relation to apolipoprotein E polymorphism. J. Neurol. Neurosurg. Psychiatry 64: 742–746.

    Google Scholar 

  • Lipsey, M. W., and Wilson, D. B. (1993). The efficacy of psychological, educational, and behavioral treatment. Am. Psychol. 12: 1181–1209.

    Google Scholar 

  • Loewenstein, D. A., Barker, W. W., Chang, J.-Y., Apicella, A., Yoshii, F., Kothari, P., et al. (1989). Predominant left hemispere metabolic dysfunction in dementia. Arch. Neurol. 46: 146–152.

    Google Scholar 

  • Luxenberg, J. S., Haxby, J. V., Creasey, H., Sundaram, M., and Rapoport, S. I. (1987). Rate of ventricular enlargement in dementia of the Alzheimer type correlates with rate of neuropsychological deterioration. Neurology 37: 1135–1140.

    Google Scholar 

  • Lyoo, I. K., Satlin, A., Lee, C. K., and Renshaw, P. F. (1997). Regional atrophy of the corpus callosum in subjects with Alzheimer's disease and multi-infarct dementia. Psychiatry Res. 74: 63–72.

    Google Scholar 

  • Matsuda, H. (2001). Cerebral blood flow and metabolic abnormalities in Alzheimer's disease. Ann. Nucl. Med. 15: 85–92.

    Google Scholar 

  • McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., and Stadlin, E. M. (1984). Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 34: 939–944.

    Google Scholar 

  • Mega, M. S., Thompson, P. M., Toga, A. W., and Cummings, J. L. (2000). Brain mapping in dementia. In: Mazziotta, J. C., Toga, A. W., and Frackowiak, R. S. J. (eds.), Brain Mapping: The Disorders, Academic Press, San Diego, CA, pp. 218–248.

    Google Scholar 

  • Meltzer, C. C., Zubieta, J. K., Brandt, J., Tune, L. E., Mayberg, H. S., and Frost, J. J. (1996). Regional hypometabolism in Alzheimer's disease as measured by positron emission tomography after correction for effects of partial volume averaging. Neurology 47: 454–461.

    Google Scholar 

  • Mentis, M. J. (2000). Positron emission tomography and single photon emission computed tomography imaging in Alzheimer's disease. Neurologist 6: 28–43.

    Google Scholar 

  • Mentis, M. J., Weinstein, E. A., Horwitz, B., McIntosh, A. R., Pietrini, P., Alexander, G. E., et al. (1995). Abnormal brain glu-cose metabolism in the delusional misidentification syndromes: A positron emission tomography study in Alzheimer disease. Biol. Psychiatry 38: 438–449.

    Google Scholar 

  • Mentis, M. J., Horwitz, B., Grady, C. L., Alexander, G. E., VanMeter, J. W., Maisog, J. M., et al. (1996). Visual cortical dysfunction in Alzheimer's disease evaluated with a temporally graded "stress test" during PET. Am. J. Psychiatry 153: 32–40.

    Google Scholar 

  • Messa, C., Perani, D., Lucignani, G., Zerorini, A., Zito, F., Rizzo, G., et al. (1994). High-resolution technetium-99m-HMPAO SPECT in patients with probably Alzheimer's disease: Comparison with fluorine-18-FDG PET. J. Nucl. Med. 35: 210–216.

    Google Scholar 

  • Meyer, M., Koeppe, R. A., Frey, K. A., Foster, N. L., and Kuhl, D. E. (1995). Positron emission tomography measures of benzodiazepine binding in Alzheimer's disease. Arch. Neurol. 52: 314–317.

    Google Scholar 

  • Mielke, R., Herholz, K., Grond, M., Kessler, J., and Heiss, W.-D. (1991). Differences of regional cerebral glucose metabolism be-tween presenile and senile dementia of Alzheimer type. Neurobiol. Aging 13: 93–98.

    Google Scholar 

  • Mielke, R., Pietrzyk, U., Jacobs, A., Fink, G. R., Ichimiya, A., Kessler, J., et al. (1994). HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: Comparison of perfusion and metabolic pattern. Eur. J. Nucl. Med. 21: 1052–1060.

    Google Scholar 

  • Mori, E., Yoneda, Y., Yamashita, H., Hirono, N., Ikeda, M., and Yamadori, A. (1997). Medial temporal structures relate to memory impairment in Alzheimer's disease: An MRI volumetric study. J. Neurol. Neurosurg. Psychiatry 63: 214–221.

    Google Scholar 

  • Murphy, D. G. M., DeCarli, C. D., Daly, E., Gillette, J. A., McIntosh, A. R., Haxby, J. V., et al. (1993). Volumetric magnetic resonance imaging in men with dementia of the Alzheimer type: Correlations with disease severity. Biol. Psychiatry 34: 612–621.

    Google Scholar 

  • Obara, K., Meyer, J. S., Mortel, K. F., and Muramatsu, K. (1994). Cognitive declines correlate with decreased cortical volume and perfusion in dementia of Alzheimer type. J. Neurol. Sci. 127: 96–102.

    Google Scholar 

  • O'Mahony, D., Coffey, J., Murphy, J., O'Hare, N., Hamilton, D., Freyne, P., et al. (1994). The discriminant value of semiquanti-tative SPECT data in mild Alzheimer's disease. J. Nucl. Med. 35: 1450–1455.

    Google Scholar 

  • Orwin, R. G. (1983). A fail safe N for effect size. J. Educ. Stat. 8: 157–159.

    Google Scholar 

  • Pálsson, S., Aevarsson, O., and Skoog, I. (1999). Depression, cerebral atrophy, cognitive performance and incidence of dementia: Population study of 85-year-olds. Br. J. Psychiatry 174: 249–253.

    Google Scholar 

  • Pantel, J., Schröder, J., Essig, M., Popp, D., Dech, H., Knopp, M. V., et al. (1997). Quantitative magnetic resonance imaging in geriatric depression and primary degenerative dementia. J. Affect. Disord. 42: 69–83.

    Google Scholar 

  • Parsey, R. V., and Krishnan, K. R. R. (1998). Quantitative analysis of T2 signal intensities in Alzheimer's disease. Psychiatry Res. Neuroimaging 82: 181–185.

    Google Scholar 

  • Pearlson, G. D., Rabins, P. V., Kim, W. S., Speedie, L. J., Moberg, P. J., Burns, A., et al. (1989). Structural brain CT changes and cognitive deficits in elderly depressives with and without reversible dementia ('pseudodementia'). Psychol. Med. 19: 573–584.

    Google Scholar 

  • Pearlson, G. D., Harris, G. J., Powers, R. E., Barta, P. E., Camargo, E. E., Chase, G. A., et al. (1992). Quantitative changes in mesial temporal volume regional cerebral blood flow, and cognition in Alzheimer's disease. Arch. Gen. Psychiatry 49: 402–408.

    Google Scholar 

  • Pfefferbaum, A., Sullivan, E. V., Jernigan, T. L., Zipursky, R. B., Rosenbloom, M. J., Yesavage, J. A., et al. (1990). A quantita-tive analysis of CT and cognitive measures in normal aging and Alzheimer's disease. Psychiatry Res. 35: 115–136.

    Google Scholar 

  • Pietrini, P., Furey, M. L., Graff-Radford, N., Freo, U., Alexander, G. E., Grady, C. L., et al. (1996). Preferential metabolic involvement of visual cortical areas in a subtype of Alzheimer's disease: Clinical implications. Am. J. Psychiatry 153: 1261–1268.

    Google Scholar 

  • Pitkänen, A., Laakso, M., Kälviäinen, R., Partanen, K., Vainio, P., Lehtovirta, M., et al. (1996). Severity of hippocampal atrophy correlates with the prolongation of MRI and T2 relaxation time in temporal lobe epilepsy but not in Alzheimer's disease. Neurology 46: 1724–1730.

    Google Scholar 

  • Prohovnik, I., Mayeux, R., Sackeim, H. A., Smith, G., Stern, Y., and Alderson, P. O. (1988). Cerebral perfusion as a diagnostic marker of early Alzheimer's disease. Neurology 38: 931–937.

    Google Scholar 

  • Riddle, W., O'Carroll, R. E., Dougall, N., Van Beck, M., Murray, C., Curran, S. M., et al. (1993). A single photon emission computerised tomography study of regional brain function underlying verbal memory in patients with Alzheimer-type dementia. Br. J. Psychiatry 163: 166–172.

    Google Scholar 

  • Rinne, J. O., Sahlberg, N., Ruottinen, H., Någren, K., and Lehikoinen, P. (1998). Striatal uptake of the dopamine reuptake ligand [11C]-CFT is reduced in Alzheimer's disease assessed by positron emission tomography. Neurology 1998: 152–156.

    Google Scholar 

  • Rosenthal, R. (1991). Meta-Analytic Procedures for Social Research, Sage, Beverly Hills, CA.

    Google Scholar 

  • Rosenthal, R. (1995). Writing meta-analytic reviews. Psychol. Bull. 118: 183–192.

    Google Scholar 

  • Russo, R., and Spinnler, H. (1994). Implicit verbal memory in Alzheimer's disease. Cortex 30: 359–375.

    Google Scholar 

  • Salat, D. H., Kaye, J. A., and Janowsky, J. S. (1999). Prefrontal gray and white matter volumes in healthy aging and Alzheimer disease. Arch. Neurol. 56: 338–344.

    Google Scholar 

  • Sandor, T., Albert, M., Stafford, J., and Harpley, S. (1988). Use of computerized CT analysis to discriminate between Alzheimer pa-tients and normal control subjects. Am. J. Neuroradiol. 9: 1181–1187.

    Google Scholar 

  • Sandor, T., Jolesz, F., Tieman, J., Kikinis, R., Jones, K., and Albert, M. (1992). Comparative analysis of computed tomography and magnetic resonance imaging scans in Alzheimer patients and controls. Arch. Neurol. 49: 381–384.

    Google Scholar 

  • Sawle, G. V. (1995). Imaging the head: Functional imaging. J. Neurol. Neurosurg. Psychiatry 58: 132–144.

    Google Scholar 

  • Schapiro, M. B., Pietrini, P., Grady, C. L., Ball, M. J., DeCarli, C., Kumar, A., et al. (1993). Reductions in parietal and temporal cerebral metabolic rates for glucose are not specific for Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry 56: 859–864.

    Google Scholar 

  • Schwartz, J. M., Aylward, E., Barta, P. E., Tune, L. E., and Pearlson, G. D. (1992). Sylvian fissure size in schizophrenia measured with magnetic resonance imaging rating protocol of the consortium to establish a registry for Alzheimer's disease. Am. J. Psychiatry 149: 1195–1198.

    Google Scholar 

  • Scinto, L. F. M., and Daffner, K. R. (2000). Early Diagnosis of Alzheimer's Disease, Humana Press, Totowa, NJ.

    Google Scholar 

  • Shear, P. K., Sullivan, E. V., Mathalon, D. H., Lim, K. O., Davis, L. F., Yesavage, J. A., et al. (1995). Longitudinal volumetric computed tomographic analysis of regional changes in normal aging and Alzheimer's disease. Arch. Neurol. 52: 392–402.

    Google Scholar 

  • Smith, G. S., de Leon, M. J., George, A. E., Kluger, A., Volkow, N. D., McRae, T., et al. (1992). Topography of cross-sectional and lon-gitudinal glucose metabolic deficits in Alzheimer's disease: Patho-physiologic implications. Arch. Neurol. 49: 1142–1150.

    Google Scholar 

  • Soininen, H., Helkala, E.-L., Kuikka, J., Hartikainen, P., Lehtovitra, M., and Riekkinen, P. J., Sr. (1995). Regional cerebral blood flow measured by 99m Tc-HMPAO SPECT differs in subgroups of Alzheimer's disease. J. Neural Transm. 9: 95–109.

    Google Scholar 

  • Spampinato, U., Habert, M. O., Mas, J. L., Bourdel, M. C., Ziegler, M., de Recondo, J., et al. (1991). (99mTc)-HM-PAO SPECT and cognitive impairment in Parkinson's disease: A comparison with dementia of the Alzheimer type. J. Neurol. Neurosurg. Psychiatry 54: 787–792.

    Google Scholar 

  • Sperling, R. A., Sandson, T. A., and Johnson, K. A. (2000). Functional imaging in Alzheimer's disease. In: Scinto, L. F. M., and Daffner, K. R. (eds.), Early Diagnosis of Alzheimer's Disease, Humana Press, Totowa, NJ, pp. 149–168.

    Google Scholar 

  • Starkstein, S. E., Migliorelli, R., Tesón, A., Sabe, L, Vázquez, S., Turjanski, M., et al. (1994). Specificity of changes in cerebral blood flow in patients with frontal lobe dementia. J. Neurol. Neurosurg. Psychiatry 57: 790–795.

    Google Scholar 

  • Stern, Y. (2002). What is cognitive reserve? Theory and research application of the reserve concept. J. Int. Neuropsychol. Soc. 8: 448–460.

    Google Scholar 

  • Stoppe, G., Staedt, J., Kögler, A., Schütze, R., Kunert, H. J., Sandrock, D., et al. (1995). 99m Tc-HMPAO-SPECT in the diagnosis of senile dementia of Alzheimer's type-A study under clinical routine conditions. J. Neural Transm. 99: 195–221.

    Google Scholar 

  • Sullivan, E. V., Shear, P. K., Mathalon, D. H., Kelvin, O. L., Yesavage, J. A., Tinklenberg, J. R., et al. (1993). Greater abnormalities of brain cerebrospinal fluid volumes in younger than in older patients with Alzheimer's disease. Arch. Neurol. 50: 359–373.

    Google Scholar 

  • Szelies, B., Grond, M., Herholz, K., Kessler, J., Wullen, T., and Heiss, W.-D. (1992). Quantitative EEG mapping and PET in Alzheimer's disease. J. Neurol. Sci. 110: 46–56.

    Google Scholar 

  • Szelies, B., Mielke, R., Herholz, K., and Heiss, W.-D. (1994). Quantitative topographical EEG compared to FDG PET for classification of vascular and degenerative dementia. Electroencephalogr. Clin. Neurophysiol. 91: 131–139.

    Google Scholar 

  • Talbot, P. R., Lloyd, J. J., Snowden, J. S., Neary, D., and Testa, H. J. (1993). Choice of reference region in the quantification of single-photon emission tomography in primary degenerative dementia. Eur. J. Nucl. Med. 21: 503–508.

    Google Scholar 

  • Tamminga, C. A., Foster, N. L., Fedio, P., Bird, E. D., and Chase, T. N. (1987). Alzheimer's disease: Lowcerebral somatostatin levels correlate with impaired cognitive function and cortical metabolism. Neurology 37: 161–165.

    Google Scholar 

  • Teipel, S. J., Hampel, H., Alexander, G. E., Schapiro, M. B., Horwitz, B., Teichberg, D., et al. (1998). Dissociation between corpus callosum atrophy and white matter pathology in Alzheimer's disease. Neurology 51: 1381–1385.

    Google Scholar 

  • Tyrrell, P. J., Sawle, G. V., Ibanez, V., Bloomfield, P. M., Leenders, K. L., Frackowiak, R. S., et al. (1990). Clinical and positron emission tomographic studies in the extrapyramidal syndrome of de-mentia of the Alzheimer type. Arch. Neurol. 47: 1318–1323.

    Google Scholar 

  • Van Dyck, C. H., Lin, C. H., Robinson, R., Cellar, J., Smith, E. O., Nelson, J. C., et al. (1997). The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease. Psychopharmacology (Berl.) 132: 217–226.

    Google Scholar 

  • Van Horn, J. D., and McManus, I. C. (1992). Ventricular enlargement in schizophrenia: A meta-analysis of studies of the ventricle:brain ratio (VBR). Br. J. Psychiatry 160: 687–697.

    Google Scholar 

  • Vermersch, P., Schelten, P., Barkhof, F., Steinling, M., and Leys, D. (1993). Evidence for atrophy of the corpus callosum in Alzheimer's disease. Eur. J. Neurol. 34: 83–86.

    Google Scholar 

  • Wagner, H. N., Jr., and Conti, P. S. (1991). Advances in medical imaging for cancer diagnosis and treatment. Cancer 67: 1121–1128.

    Google Scholar 

  • Wahlund, L.-O., Andersson-Lundman, G., Basun, H., Almkvist, O., Björkstén, K. S., Sääf, J., et al. (1993). Cognitive functions and brain structures: Aquantitative study of CSF volumes on Alzheimer patients and healthy control subjects. Magn. Reson. Imaging 11: 169–174.

    Google Scholar 

  • Waldemar, G., Brunh, P., Kristensen, M, Johnsen, A., Paulson, O. B., and Lassen, N. A. (1994). Heterogeneity of neocortical cerebral blood flow deficits in dementia of the Alzheimer type: A [99mTc]-d, l-HMPAO SPECT study. J. Neurol. Neurosurg. Psychiatry 57: 285–295.

    Google Scholar 

  • Wolf, F. M. (1986). Meta-Analysis: Quantitative Methods for Research Synthesis, Sage, Newbury Park, CA.

    Google Scholar 

  • Yamauchi, H., Fukuyama, H., Harada, K., Nabatame, H., Ogawa, M., Ouchi, Y., et al. (1993). Callosal atrophy parallels decreased cortical oxygen metabolism and neuropsychological impairment in Alzheimer's disease. Arch. Neurol. 50: 1070–1074.

    Google Scholar 

  • Zakzanis, K. K. (1998a). Brain is related to behavior (p <. 05). J. Clin. Exp. Neuropsychol. 20: 419–427.

    Google Scholar 

  • Zakzanis, K. K. (1998b). Quantitative evidence for neuroanatomic and neuropsychological markers in dementia of the Alzheimer's type. J. Clin. Exp. Neuropsychol. 20: 259–269.

    Google Scholar 

  • Zakzanis, K. K. (2001). Statistics to tell the truth, the whole truth, and nothing but the truth: Formulae, illustrative numerical examples, and heuristic interpretation of effect size analyses for neuropsychological researchers. Arch. Clin. Neuropsychol. 16: 653–667.

    Google Scholar 

  • Zakzanis, K. K., Leach, L., and Kaplan, E. (1999). Neuropsycho-logical Differential Diagnosis, Swets and Zeitlinger, Lisse, The Netherlands.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Life Sciences, University of Toronto, Toronto, Ontario, Canada

    Konstantine K. Zakzanis & Zachariah Campbell

  2. Imaging/Bioengineering Research, Sunnybrook & Women's College Health Science Centre, Toronto, Ontario, Canada

    Konstantine K. Zakzanis & Simon J. Graham

  3. Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada

    Simon J. Graham

  4. Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Simon J. Graham

Authors
  1. Konstantine K. Zakzanis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Simon J. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zachariah Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Konstantine K. Zakzanis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zakzanis, K.K., Graham, S.J. & Campbell, Z. A Meta-Analysis of Structural and Functional Brain Imaging in Dementia of the Alzheimer's Type: A Neuroimaging Profile. Neuropsychol Rev 13, 1–18 (2003). https://doi.org/10.1023/A:1022318921994

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022318921994

Search

Navigation