Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease

Abstract

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 (99m)Tc-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.

Intelligence quotient–adjusted memory impairment is associated with abnormal single photon emission computed tomography perfusion

“…Similar findings have also been reported in mild AD (Johnson et al, 2001). More recently, evidence of early AD pathology in these regions was confirmed among MCI patients who came to autopsy (Bradley et al, 2002;Markesbery et al, 2006;Petersen et al, 2006). The temporoparietal perfusion abnormalities noted in our IQ-MI subjects at baseline suggest that AD pathology may have been present at the time of initial evaluation in normal CDR0 subjects.…”

Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or Moderate Alzheimer's Disease

“…Their contribution to an imaging diagnosis in AD is the pattern of reduction in blood flow or glucose uptake in areas of the brain typically affected by tau aggregation pathology [36]. While both provide indirect measures of normal brain metabolic activity (i.e., oxygen and glucose consumption respectively), their ability to demonstrate deficits due to neuropathology is similar [36,37]. The spatial resolution of PET is higher, but by using voxel-based image analysis methods (as was the case in the present study), both have comparable accuracy [38].…”

“…Deficits shown by HMPAO-SPECT in brain regions affected by tau aggregation pathology have been shown to correlate with tau aggregation pathology as measured by Braak stage [36]. The ROI and SPM analyses of rCBF decline provide a mapping of the regions of treatment benefit to those known to be particularly rich in tangles, notably medial temporal lobe structures and temporoparietal regions [39].…”

Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study

“…Only recently has it been suggested that younger AD patients might also have early synaptic loss in the PCC and precuneus [35] and that there might be precuneus volume loss in younger AD patients [36]. In a study that combined single photon emission CT (SPECT) with post-mortem Braak staging [37], hypometabolism of the precuneus was found in patients who were classified as belonging to either the Braak entorhinal or limbic stage (i.e. mild AD changes).…”