Relationships between cognitive impairment on ADAS-cog and regional cerebral blood flow using SPECT in late-onset Alzheimer’s disease
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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.
KeywordsSPECT Late-onset Alzheimer’s disease ADAS rCBF
Compliance with ethical standards
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.
- 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
- 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 9:1118–1127CrossRefPubMedGoogle 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 26:556–566CrossRefGoogle 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 45:1450–1457PubMedGoogle 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 60:1083–1091CrossRefPubMedPubMedCentralGoogle 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 163:597–603CrossRefPubMedGoogle 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 262:1238–1246CrossRefPubMedGoogle 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 32:1186–1192CrossRefGoogle 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 14:81Google 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 7:64CrossRefPubMedPubMedCentralGoogle Scholar