The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer's disease: A longitudinal SPECT study
Introduction
Alzheimer's disease (AD) is a heterogenous disease. The rate of cognitive deterioration during the course of AD varies considerably between individuals. Several studies suggest that age at onset, education level, occupational attainment, medical comorbid diseases, and presence of extrapyramidal signs and psychosis can affect the progression of cognitive deterioration [1], [2], [3], [4], [5], [6]. However, it is controversial whether these factors can be useful variables in predicting the longitudinal course of AD. Some investigators have examined a possible relation between the rate of cognitive decline and regional cerebral blood flow (rCBF) and metabolism patterns using single photon emission CT (SPECT) [7], [8], [9], [10], [11] and positron emission tomography (PET) [12], [13]. However, results of cerebral subregion correlates of clinical progression have been inconsistent. Moreover, there have been few longitudinal SPECT or PET studies in relation to cognitive and functional decline over time [8], [11]. In addition, previous studies included patients who never used cholinesterase inhibitors. Since the majority of patients have currently been treated with cholinesterase inhibitors, we should take into consideration the effect of medication on clinical progression.
In the present study, we first examined the differences in rCBF deficits at initial evaluation between rapidly progressing and slowly progressing groups and then compared rCBF changes between initial and follow-up SPECT studies in each group to determine cerebral correlates of the progression of cognitive deterioration in patients with AD.
Section snippets
Patients
We enrolled 48 patients with AD (19 men and 29 women, mean age 76.1 ± 6.0 years) attending the Memory Clinic at Tokyo Medical University Hospital. Patients with AD met clinical criteria for probable AD established by the National Institute of Neurological and Communicative Disorders Association [14]. All patients had mild to moderate AD defined by a Clinical Dementia Rating (CDR) score of 1 or 2 [15]. Patients underwent detailed general physical, neurological, and psychiatric examinations,
Results
Table 1 summarizes the clinical and demographic characteristics of the rapidly progressing (mean 2.9 ± 0.9 annual MMSE score change) and slowly progressing (mean 1.1 ± 0.6 annual MMSE score change) groups. There were no significant differences in terms of age (at the initial evaluation), gender, duration of disease, education, initial MMSE, and follow-up time between the two groups. MMSE scores at last evaluation decreased significantly in the rapidly progressing and slowly progressing groups and
Discussion
We found that the rapidly progressing group had greater rCBF deficits at initial evaluation mainly in the right parietotemporal and frontal lobes and left posterior cingulate region than did the slowly progressing group. There was a significant correlation between annual MMSE score changes and mean z-scores in the parietotemporal, posterior cingulate, and fusiform gyrus at initial SPECT. Moreover, when compared with the initial SPECT, follow-up SPECT study showed a significant rCBF reduction in
Acknowledgements
We thank K. Hirayama and H. Hirose of the Department of Nuclear Medicine of Tokyo Medical University, for their support and technical assistance. We are also grateful to Professor J. Patrick Barron of the International Medical Communications Center of Tokyo Medical University for his review of the manuscript.
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