Brain, Vol. 125, No. 8, 1772-1781,
August 2002
© 2002 Guarantors of Brain
Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer’s disease
1 Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology and Radcliffe Infirmary, 2 Department of Radiology, Radcliffe Infirmary, University of Oxford, Oxford, UK
Correspondence to: K. M. Bradley, OPTIMA, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK E-mail: kevin.bradley{at}radiology.ox.ac.uk
Reductions in regional cerebral perfusion, particularly in the posterior temporo-parietal lobes, are well recognized in Alzheimer’s disease. We set out to correlate perfusion changes, using 99mTc-HMPAO single photon emission tomography (SPET), with the pathological stage of Alzheimer’s disease. The ‘Braak stage’ of the distribution of neurofibrillary pathology in post-mortem brains was used to classify SPET scans taken in life from a mixed (dementia and control) elderly population into the entorhinal stage (n = 23 subjects), limbic stage (n = 30 subjects) and neocortical stage (n = 36 subjects) Alzheimer’s disease pathology. The SPET scans were then registered to a common, standard Talaraich space, and single template scans produced for each pathological stage. Comparison of these templates revealed an evolution in the pattern of reduction in regional perfusion. Additional comparisons were performed using earlier SPET scans obtained 5 years before death. For comparisons between templates, a threshold of 10% perfusion change was chosen so as to be clinically relevant as well as statistically significant. Reduced perfusion appears between the entorhinal and limbic stages in the anterior medial temporal lobe, subcallosal area, posterior cingulate cortex, precuneus and possibly the supero-anterior aspects of the cerebellar hemispheres. Large posterior temporo-parietal perfusion defects then appear between the limbic and neocortical stages, before finally large frontal lobe perfusion defects. The time course of these perfusion defects appears relatively long, suggesting that perfusion changes may have scope to be a diagnostic aid in staging Alzheimer’s disease in life. The reduction in anterior medial temporal lobe perfusion may have future relevance on modern high resolution SPET and PET systems and also perfusion-type MRI sequences.
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