Skip to main content

Advertisement

Log in

Relationships between cognitive impairment on ADAS-cog and regional cerebral blood flow using SPECT in late-onset Alzheimer’s disease

  • Neurology and Preclinical Neurological Studies - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

The aim of this study was to examine brain hypoperfusion and its relationship with cognitive dysfunction in late-onset Alzheimer’s disease (AD). Forty patients with late-onset AD and not receiving acetylcholinesterase inhibitors were recruited from outpatient clinics. We examined cognitive function using the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and brain perfusion using single-photon emission computed tomography, and analyzed classified gyrus level segments with three-dimensional stereotactic surface projection and the stereotactic extraction estimation method level 3. ADAS-cog subscales were grouped into three domains: language, memory, and praxis. Patients with late-onset AD showed an apparent reduction in regional cerebral blood flow (rCBF) with a z score >1.5 in the frontal, temporal, and limbic lobes, with lesser reduction in the parietal and occipital lobes. Although hypoperfusion in the orbital, rectal, and subcallosal gyri of the frontal lobe was prominent, rCBF in the inferior frontal gyrus of the frontal lobe was significantly correlated with ADAS-cog total and language and praxis subscale scores. The parahippocampal gyrus of the limbic lobe was also significantly correlated with the ADAS-cog total, language, and praxis subscale scores. Additionally, the cingulate of the limbic lobe was significantly related with ADAS-cog memory. In spite of lesser hypoperfusion, the posterior cingulate gyrus of the limbic lobe was significantly related with ADAS-cog total, language, and memory subscale scores. Further, each subdivision of ADAS-cog was found to be related with various brain regions.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • American Psychiatric Association (1994) Diagnostic and statistic manual of mental disorders (DSN-IV-TR), 4th edn. American Psychiatric Press, Washington DC (text rev)

    Google Scholar 

  • Balsis S, Unger AA, Benge JF, Geraci L, Dooby RS (2012) Gaining precision on the Alzheimer’s Disease Assessment Scale-cognitive: a Comparison of item response theory-based scores and total scores. Alzheimer’s Dement 8:288–294

    Article  Google Scholar 

  • Bartenstein P, Minoshima S, Hirsch C, Buch K, Willoch F, Mösch D, Schad D, Schwaiger M, Kurz A (1997) Quantitative assessment of cerebral blood flow in patients with Alzheimer’s disease by SPECT. J Nucl Med 38:1095–1101

    CAS  PubMed  Google Scholar 

  • Benge JF, Balsis S, Geraci L, Massman PJ, Doody RS (2009) How well do the ADAS-cog and its subscales measure cognitive dysfunction in Alzheimer’s disease? Dement Geriatr Cogn Disord 28:63–69

    Article  CAS  PubMed  Google Scholar 

  • Cavedo E, Pievani M, Boccardi M, Galluzzi S, Bocchetta M, Bonetti M, Thompson PM, Frisoni GB (2014) Medial temporal atrophy in early and late-onset Alzheimer’s disease. Neurobiol Aging 35:2004–2012

    Article  PubMed  PubMed Central  Google Scholar 

  • Dubois B, Feldman HH, Jacova C, Cummings JL, DeKosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O’Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P (2010) Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol 9:1118–1127

    Article  PubMed  Google Scholar 

  • Elgh E, Sundström T, Näsman B, Åhlström KR, Nyberg L (2002) Memory functions and rCBF 99 mTc-HMPAO SPET: developing diagnostics in Alzheimer’s disease. Eur J Nucl Med 29:1140–1148

    Article  CAS  Google Scholar 

  • Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinicians. J Psychiatr Res 12:189–198

    Article  CAS  PubMed  Google Scholar 

  • Frisoni GB, Pievani M, Testa C, Sabattoli F, Bresciani L, Bonetti M, Beltramello A, Hayashi KM, Toga AW, Thompson PM (2007) The topography of grey matter involvement in early and late onset Alzheimer’s disease. Brain 130:720–730

    Article  PubMed  Google Scholar 

  • Frlich L, Eilles R, Ihl K, Maurer K, Lanczik M (1989) Stage-dependent reduction of regional cerebral blood flow measured by HMPAO-SPECT in dementia of Alzheimer type. Psychiatry Res 29:347–350

    Article  CAS  PubMed  Google Scholar 

  • Grady CL, Haxby JV, Horwitz B, Berg G, Rapoport SI (1987) Neuropsychological and cerebral metabolic function in early vs late onset dementia of the Alzheimer type. Neuropsychologia 25:807–816

    Article  CAS  PubMed  Google Scholar 

  • Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, Symon L (1975) Cerebral blood flow in dementia. Arch Neurol 32:632–637

    Article  CAS  PubMed  Google Scholar 

  • Hanaoka T, Kimura N, Aso Y, Takemaru M, Kimura Y, Ishibashi M, Matsubara E (2015) Relationship between white matter lesions and regional cerebral blood flow changes during longitudinal follow up in Alzheimer’s disease. Geriatr Gerontol Int 16:836–842

    Article  PubMed  Google Scholar 

  • Hanyu H, Sato T, Hirao K, Kanetaka H, Iwamoto T, Koizumi K (2010) The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer’s disease: a longitudinal SPECT study. J Neurol Sci 290:96–101

    Article  PubMed  Google Scholar 

  • Hirano N, Mori E, Ishii K, Ikejiri Y, Imamura T, Shimomura T, Hashimoto M, Yamashita H, Sasaki M (1998) Hypofunction in the posterior cingulate gyrus correlates with disorientation for time and place in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 64:552–554

    Article  Google Scholar 

  • Holman BL, Johnson KA, Gerada B, Carvalho PA, Satlin A (1992) The scintigraphic appearance of Alzheimer’s disease: a prospective study using technetium-99m-HMPAO SPECT. J Nucl Med 33:181–185

    CAS  PubMed  Google Scholar 

  • Hongo J, Nakaaki S, Shinagawa Y, Murata Y, Sato J, Tatsumi H, Tohyama J, Soma T, Iidaka T, Fukui T, Mimura M, Furukawa T (2008) SPECT-identified neuroanatomical predictor of the cognitive effects of donepezil treatment in patients with Alzheimer’s disease. Dementia Geriatr Cog Disord 26:556–566

    Article  CAS  Google Scholar 

  • Imabayashi E, Matsuda H, Asada T, Ohnishi T, Sakamoto S, Nakano S, Inoue T (2004) Superiority of 3-dimensional stereotactic surface projection analysis over visual inspection in discrimination of patients with very early Alzheimer’s disease from controls using brain perfusion SPECT. J Nucl Med 45:1450–1457

    PubMed  Google Scholar 

  • Ishii K, Willoch F, Minoshima S, Drzezga A, Ficaro EP, Cross DJ, Kuhl DE, Schwaiger M (2001) Statistical brain mapping of 18F-FDG PET in Alzheimer’s disease: validation of anatomic standardization for atrophied brains. J Nucl Med 42:548–557

    CAS  PubMed  Google Scholar 

  • Ishii K, Kawachi T, Sasaki H, Kono AK, Fukuda T, Kojima Y, Mori E (2005) Voxel-based morphometric comparison between early- and late-onset mild Alzheimer’s disease and assessment of diagnostic performance of Z score images. Am J Neuroradiol 26:333–340

    PubMed  Google Scholar 

  • Kaiser NC, Melrose RJ, Liu C, Sultzer DL, Jimenez E, Su M, Monserratt L, Mendez MF (2012) Neuropsychological and neuroimaging markers in early versus late-onset Alzheimer’s disease. Am J Alzheimers Dis Other Demen 27:520–529

    Article  PubMed  PubMed Central  Google Scholar 

  • Kemp PM, Holmes C, Hoffmann SM, Bolt L, Holmes R, Rowden J, Fleming JS (2003) Alzheimer’s disease: differences in technetium-99m HMPAO SPECT scan findings between early onset and late onset dementia. J Neurol Neurosurg Psychiatry 74:715–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim EJ, Cho SS, Jeong Y, Park KC, Kang SJ, Kang E, Kim SE, Lee KH, Na DL (2005) Glucose metabolism in early onset versus late onset Alzheimer’s disease: an SPM analysis of 120 patients. Brain 128:1790–1801

    Article  CAS  PubMed  Google Scholar 

  • Kuczynski B, Reed B, Mungas D, Weiner M, Chui HC, Jagust W (2008) Cognitive and anatomic contributions of metabolic decline in Alzheimer disease and cerebrovascular disease. Arch Neurol 65:650–655

    Article  PubMed  PubMed Central  Google Scholar 

  • Kumar A, Schapiro MB, Grady C, Haxby JV, Wagner E, Salerno JA, Friedland RP, Rapoport SI (1991) High-resolution PET studies in Alzheimer’s disease. Neuropsychopharmacology 4:35–46

    CAS  PubMed  Google Scholar 

  • Kume K, Hanyu H, Sato T, Hirao K, Shimizu S, Kanetaka H, Sakurai H, Iwamoto T (2011) Vascular risk factors are associated with faster decline of Alzheimer disease: a longitudinal SPECT study. J Neurol 258:1295–1303

    Article  PubMed  Google Scholar 

  • Li W, Antuono PG, Xie C, Chen G, Jones JL, Ward BD, Franczak MB, Goveas JS, Li SJ (2012) Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer’s disease after 12-week donepezil treatment. Neuroimage 60:1083–1091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKeith IG, Bartholomew PH, Irvine EM, Cook J, Adams R, Simpson AE (1993) Single photon emission computerised tomography in elderly patients with Alzheimer’s disease and multi-infarct dementia. Regional uptake of technetium-labelled HMPAO related to clinical measurements. Br J Psychiatry 163:597–603

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE (1995) A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 36:1238–1248

    CAS  PubMed  Google Scholar 

  • Mizumura S, Kumita S, Cho K, Ishihara M, Nakajo H, Toba M, Kumazaki T (2003) Development of quantitative analysis method for stereotactic brain image: assessment of reduced accumulation in extent and severity using anatomical segmentation. Ann Nucl Med 17:289–295

    Article  PubMed  Google Scholar 

  • Möller C, Vrenken H, Jiskoot L, Versteeg A, Barkhof F, Scheltens P, van der Flier WM (2013) Different patterns of gray matter atrophy in early-and late-onset Alzheimer’s disease. Neurobiol Aging 34:2014–2022

    Article  PubMed  Google Scholar 

  • Montaldi D, Brooks DN, McColl JH, Wyper D, Patterson J, Barron E, McCulloch J (1990) Measurements of regional cerebral blood flow and cognitive performance in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 53:33–38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nobili F, Brugnolo A, Calvini P, Copello F, De Leo C, Girtler N, Morbelli S, Piccardo A, Vitali P, Rodriguez G (2005) Resting SPECT-neuropsychology correlation in very mild Alzheimer’s disease. Clin Neurophysiol 116:364–375

    Article  CAS  PubMed  Google Scholar 

  • O’Brien JT, Eagger S, Syed GM, 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Palasí A, Gutiérrez-Iglesias B, Alegret M, Pujadas F, Olabarrieta M, Liébana D, Quintana M, Álvarez-Sabín J, Boada M (2015) Differentiated clinical presentation of early and late-onset Alzheimer’s disease: is 65 years of age providing a reliable threshold? J Neurol 262:1238–1246

    Article  PubMed  Google Scholar 

  • Reisberg B, Ferris SH, Anand R, de Leon MJ, Schneck MK, Buttinger C, Borenstein J (1984) Functional staging of dementia of the Alzheimer’s type. Ann NY Scad Sci 435:481–483

    Article  Google Scholar 

  • Rodriguez G, Morbelli S, Brugnolo A, Calvini P, Girtler N, Piccardo A, Dougall NJ, Ebmeier KP, Baron JC, Nobili F (2005) Global cognitive impairment should be taken into account in SPECT-neuropsychology correlations: the example of verbal memory in very mild Alzheimer’s disease. Eur J Nucl Med Mol Imag 32:1186–1192

    Article  CAS  Google Scholar 

  • Rosen WG, Mohs RC, Davis L (1984) A new rating scale for Alzheimer’s disease. Am J Psychiatry 141:1356–1364

    Article  CAS  PubMed  Google Scholar 

  • Sá F, Pinto P, Cunha C, Lemos R, Letra L, Simões M, Santana I (2012) Differences between early and late-onset Alzheimer’s disease in neuropsychological tests. Front Neurol 14:81

    Google Scholar 

  • Sakamoto S, Ishii K, Sasaki M, Hosaka K, Mori T, Matsui M, Hirano N, Mori E (2002) Differences in cerebral metabolic impairment between early and late onset types of Alzheimer’s disease. J Neurol Sci 200:27–32

    Article  CAS  PubMed  Google Scholar 

  • Smits LL, Pijnenburg YA, Koedam EL, van der Vlies AE, Reuling IE, Koene T, Teunissen CE, Scheltens P, van der Flier WM (2012) Early onset Alzheimer’s disease is associated with a distinct neuropsychological profile. J Alzheimers Dis 30:101–108

    PubMed  Google Scholar 

  • Song I, Chung Y, Chung S, Jeong J (2014) Early diagnosis of Alzheimer’s disease and Parkinson’s disease associated with dementia using cerebral perfusion SPECT. Dement Geriatr Cogn Disord 37:276–285

    Article  PubMed  Google Scholar 

  • Tippett WJ, Black SE (2008) Regional cerebral blood flow correlates of visuospatial tasks in Alzheimer’s disease. J Int Neuropsychol Soc 14:1034–1045

    Article  PubMed  Google Scholar 

  • Verma N, Beretvas SN, Pascual B, Masdeu JC, Markey MK (2015) The Alzheimer’s disease neuroimaging initiative. New scoring methodology improves the sensitivity of the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) in clinical trials. Alzheimers Res Ther 7:64

    Article  PubMed  PubMed Central  Google Scholar 

  • Waldemar G, Bruhn P, Kristensen M, Johnson A, Paulson OB, Lassen NA (1994) Heterogeneity of neocortical cerebral blood flow deficits in dementia of the Alzheimer type: a [99Tc]-d, l-HMPAO SPECT study. J Neuro Neurosurg Psychiatry 57:285–295

    Article  CAS  Google Scholar 

  • Yamashita K, Taniwaki Y, Utsunomiya H, Taniwaki T (2014) Cerebral blood flow reduction associated with orientation for time in amnesic mild cognitive impairment and Alzheimer disease patients. J Neuroimaging 24:590–594

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yukihiko Shirayama.

Ethics declarations

Funding

This research received no specific Grant from any funding agency or from commercial or not-for-profit sectors.

Conflict of interest

Dr. Shirayama has received research support from Eli Lilly, Eisai, MSD, Pfizer, and Mitsubishi-Tanabe. Dr. Okubo has received research support from Eisai, Bayer, and Daiichi Sankyo. Dr. Takahashi and Dr. Oda have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takahashi, M., Oda, Y., Okubo, T. et al. Relationships between cognitive impairment on ADAS-cog and regional cerebral blood flow using SPECT in late-onset Alzheimer’s disease. J Neural Transm 124, 1109–1121 (2017). https://doi.org/10.1007/s00702-017-1734-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-017-1734-7

Keywords

Navigation