IC‐P‐144: Cerebrovascular Reserve, Dementia Risk and Renal Function

Background: Relationships among dementia risk factors are well established: diabetes and related complications, nephropathy and retinopathy, coexist with hypertension, obesity and coronary disease. Increasing evidence implicates brain hypoperfusion as an early and potentially treatable aspect of dementia risk. In this context, the relation of renal dysfunction to cerebrovascular reserve is pertinent in vascular risk subgroups, as well as brain trauma and metal toxicity. Methods: Outpatients (60% women, 40% men; 65% Caucasian; ages 25-91 years, average 55+-10 years,) with cerebral ischemia or related symptoms (eg. TIA, cognitive impairment, post concussion, complex migraine) were injected with radiolabelled tracers, followed brain SPECT. Cortical metabolic and perfusion indices (CMi, CPi) for basal and perfusion-stimulated SPECT were scaled similarly to rest and stress ventricular ejection fractions: normal CMi 50-72%, normal CPi 53-75% and normal cerebrovascular reserve (CR) if CPi > (CMi+3)%. Quantitative urine porphyrins screened for metal toxicity. Renal function was calculated by MRDD. Patients with type 2 diabetes were treated to average HbA1c 8%; blood pressures were treated to < 140/90 mm Hg. Results: CR was abnormal in 64% (51/80) of hypertensives, 61% (54/89) of diabetics, 64% (32/50) of insulin resistant nondiabetics, 57% (16/28) of mild brain trauma patients and 58% (42/78) of metal toxic patients. CR was abnormal in 50% (1/2) of patients with GFR < 15 ml/min; but normal in 90% (18/20) of patients with GFR 15 to 60 ml/min. In each risk group, mean age did not differ between patients with normal versus abnormal CR. Conclusions: Abnormal CR is a fundamental aspect of disorders predisposing to dementia, including diabetes, hypertension, insulin resistance, metal toxicity and brain trauma. Renal dysfunction unexpectedly correlates inversely with abnormal CR, possibly because of an artifact (eg. a greater perfusion-stimulated cerebral arterial input function, if uncorrected for renal failure). Hence, high prevalence of abnormal CR typical of dementia may be underestimated, particularly in conditions associated with renal failure, such as metal toxicity, diabetes and hypertension. Fig. 1 (Above, Left): Axial SPECT slices are defined parallel to the brain long axis from occipital to prefrontal. For the Cortical Metabolic index (CMi), one or more axial slices are centered one third of the way from the top of the brain, just superior to the roof of the normal-sized lateral ventricles. Activity display uses a Sokoloff color scale, with white for peak brain, black for zero and spectral colors for intermediate activities. Computerselected isocontours define areas that contain activity above a certain fraction of the peak activity. The 30% isocontour represents total brain activity in that axial slice, chosen slightly outside the actual external edge of the brain (usually near a 60% isocontour) to correct for attenuation. The 60% isocontour represents the edge of normally functioning neurons, and the Cortical Metabolic index (CMi), calculated as the ratio of activity within the 60% to that within the 30% isocontours, is a measure of the fraction of brain function due to normal neuronal function. The Cortical Perfusion index (CPi) is similarly calculated from 60% and 30% isocontours after the patient has receives a cerebral perfusion stimulant such as 0.5 to 1 g acetazolamide IV or 0.4 to 0.8 mg nitroglycerin