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Single SPECT Measures of Cerebral Cortical Perfusion Reflect Time-Index Estimation of Dementia Severity in Alzheimer's Disease

Departments of Psychiatry, Neurology, Diagnostic Radiology, and Statistics and the Alzheimer's Disease Research Center of the National Institute on Aging, Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington
Mental Health, Nuclear Medicine, Medicine, and Nursing Services, Veterans Affairs Medical Center, Lexington, Kentucky

Correspondence: For correspondence or reprints contact: J. Wesson Ashford, MD, PhD, Department of Psychiatry, College of Medicine, University of Kentucky, 3470 Blazer Pkwy., Lexington, KY 40509.

ABSTRACT

To determine the relationship between cerebral cortical blood flow loss and the temporal development of the dementia in Alzheimer's disease (AD), SPECT was studied in a cross section of AD patients with a broad range of impairment. Methods: Thirty patients with a diagnosis of probable AD had their mini-mental state examination scores transformed into time-index values to give an estimation of dementia severity relative to the developmental time course. SPECT images were obtained using ^99mTc-ethyl cysteinate dimer and a 3-head camera. Cortical surface perfusion was analyzed, including modified Talairach standardization, to obtain cortical elements from the convexity (each representing about 0.25 cm² at the surface, 6.6-mm cortical depth) referenced to the mean perfusion of the full greater cerebellar hemisphere. These element ratios were analyzed (individually and by averages of estimated Brodmann's areas and brain regions) using linear regression with the time-index value. Results: For individual posterotemporal and inferoparietal Brodmann's areas (21, 22 and 39, 40, respectively) the correlation coefficients between cortical perfusion ratios and dementia severity ranged between –0.67 and –0.78 (P < 0.001). Perfusion ratios from these regions declined 2.5%–4.2% for each estimated year of progression. Prefrontal area perfusion showed less association with severity. Perfusion in primary cortical regions had no significant association with dementia severity. Conclusion: Cerebral cortical perfusion loss is temporally related to development of dementia. The spatial pattern of high, significant correlations between cortical perfusion and dementia severity shows a regional distribution that corresponds closely to the distribution of AD pathology described in autopsy studies.

Key Words: Alzheimer's disease • SPECT • computer-assisted image processing • cognitive dysfunction • dementia severity

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