Premium
IC‐P‐145: Effect of APOE4 Status and Alzheimer's Disease on Posterior Cingulate Connectivity
Author(s) -
Machulda Mary M.,
Jones David T.,
McDade Eric M.,
Vemuri Prashanthi,
Avula Ramesh,
Przybelski Scott A.,
Younkin Steven,
Senjem Matt,
Gunter Jeff,
Boeve Bradley F.,
Knopman David,
Petersen Ronald C.,
Jack Clifford R.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.160
Subject(s) - posterior cingulate , default mode network , precuneus , cuneus , neuroscience , alzheimer's disease , resting state fmri , temporal lobe , functional connectivity , cortex (anatomy) , occipital lobe , psychology , medicine , functional magnetic resonance imaging , disease , epilepsy
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 (e.g., TIA, cognitive impairment, post concussion, complex migraine) were injected with radiolabelled tracers, followed by brain SPECT. Cortical metabolic and perfusion indices (CMi, CPi) for basal and perfusion-stimulated SPECT were scaled similarly to rest and stress left 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 HgbA1c 8%; blood pressures were treated to < 140/90 mmHg. 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) 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.