The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer's disease: A longitudinal SPECT study

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Abstract

Background and purpose

The progression of cognitive deterioration in patients with Alzheimer's disease (AD) is considerably variable. The ability to predict the progression rate is important for clinicians to treat and manage patients with AD. We examined the possible relationship between the rate of cognitive deterioration and regional cerebral blood flow (rCBF) patterns in patients with AD.

Methods

We followed 48 patients with AD for an average of 37 months. They were subsequently divided into the rapidly progressing group (n = 24) and slowly progressing group (n = 24) based on an annual Mini-Mental State Examination (MMSE) score change. Initial and follow-up rCBF were assessed using single photon emission CT (SPECT) and the SPECT data were analyzed by 3D-stereotactic surface projections.

Results

At initial evaluation, the rapidly progressing group had greater rCBF deficits mainly in the parietotemporal and frontal regions, and left posterior cingulate than did the slowly progressing group. When compared with initial SPECT, follow-up SPECT showed a significant rCBF reduction in widespread regions, including parietotemporal and frontal lobes, of the rapidly progressing group, while showed in the scattered and small regions of hemispheres of the slowly progressing group.

Conclusion

Our longitudinal SPECT study suggests a significant association between rCBF deficits in the parietotemporal, posterior cingulate, and frontal regions and subsequent rapid cognitive and rCBF deterioration.

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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