Peter C. O’Brien

DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment

The authors assessed whether measures of hippocampal water diffusivity at baseline can predict future progression to Alzheimer disease (AD) in amnestic mild cognitive impairment (aMCI). Higher baseline hippocampal diffusivity was associated with a greater risk of progression to AD in aMCI (p = 0.002). Magnetic resonance diffusion-weighted imaging may help identify patients with aMCI who will progress to AD as well as or better than structural MRI measures of hippocampal atrophy.

Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer’s disease

Magnetic resonance (MR)-based volume measurements of atrophy are potential markers of disease progression in patients with amnestic mild cognitive impairment (MCI) and Alzheimers disease (AD). Longitudinal changes in (1)H MR spectroscopy ((1)H MRS) metabolite markers have not been characterized in MCI subjects. Our objective was to determine the longitudinal (1)H MRS metabolite changes in patients with MCI, and AD, and to compare (1)H MRS metabolite ratios and ventricular volumes in tracking clinical disease progression in AD. The neuronal integrity marker N-acetylaspartate/creatine ratio declined in MCI and AD patients compared to cognitively normal elderly. The change in (1)H MRS metabolite ratios correlated with clinical progression about as strongly as the rate of ventricular expansion, suggesting that (1)H MRS metabolite ratios may be useful markers for the progression of AD. Choline/creatine ratio declined in stable MCI, compared to converter MCI patients and cognitively normal elderly, which may be related to a compensatory mechanism in MCI patients who did not to progress to AD.

Reliability of the Questionnaire for Verifying Stroke-Free Status

Background: The Questionnaire for Verifying Stroke-Free Status (QVSS) is a practical instrument for confirming absence of previous symptomatic stroke or transient ischemic attack in control subjects participating in stroke research. Methods: We tested reliability of telephone administration of the QVSS in stroke patients and healthy volunteers aged ≧50 years. For intrarater reliability, one interviewer administered the QVSS twice to the same subjects 8 weeks apart (115 subjects). For interrater reliability, one interviewer administered the QVSS and a different interviewer readministered the QVSS 8 weeks later (107 subjects). Both interviewer and interviewee were masked to responses from the first interview. Results: Intrarater agreement for overall classification of stroke-free status was 0.90 [95% confidence interval (CI), 0.82–0.94], with a ĸ of 0.78 (95% CI, 0.67–0.90). Interrater agreement for overall classification was 0.94 (95% CI, 0.88–0.98), with a ĸ of 0.89 (95% CI, 0.80–0.97). Conclusion: The QVSS is a reliable instrument for telephone interviews in stroke research when applied to adult populations without severe deficits of cognition or verbal communication.

Familial Clustering of Stroke According to Proband Age at Onset of Presenting Ischemic Stroke

Background and Purpose— The magnitude of inherited risk of stroke may lessen with age, and this would have implications for optimizing genomic approaches to identifying genetic risk factors for stroke. We investigated the relationship between age and inherited risk of stroke. Methods— Family histories of stroke were obtained in systematic interviews with 310 adult men and women with recent CT- or MR-confirmed ischemic stroke. Probability of stroke in first-degree relatives was analyzed by logistic regression, adjusting for sibship size. Results— The probability of having a sibling with stroke increased as proband age at stroke presentation increased. Per decade increase in proband age, the odds ratio was 1.65 (95% confidence interval [CI], 1.20 to 2.28; P =0.002) for a concordant sibling and 1.69 (95% CI, 1.15 to 2.49; P =0.008) for ≥2 first-degree relatives with a history of stroke. Conclusions— Clustering of stroke was not greater in families with probands manifesting symptoms of stroke in earlier than later adulthood. The relationship between proband age and positive family history of stroke does not suggest an upper age-limit cutoff for genomewide linkage studies.

Evaluation of the posology of pindolol therapy of hypertension with automatic indirect ambulatory blood pressure monitoring

Pindolol, a nonselective β-adrenergic blocking drug, lowered systolic and diastolic blood pressure equally well during once daily and twice daily dosage. Absence of supine bradycardia likely was attributable to the intrinsic sympathomimetic activity of pindolol. Automatic ambulatory blood pressure monitoring reliably confirmed office blood pressure recordings and indicated good control throughout the day and night.

Modeling Chronic Glycemic Exposure Variables as Correlates and Predictors of Microvascular Complications of Diabetes: Response to Orchard et al.

OBJECTIVE The degree to which chronic glycemic exposure (CGE) (fasting plasma glucose [FPG], HbA1c [A1C], duration of diabetes, age at onset of diabetes, or combinations of these) is associated with or predicts the severity of microvessel complications is unsettled. Specifically, we test whether combinations of components correlate and predict complications better than individual components. RESEARCH DESIGN AND METHODS Correlations and predictions of CGE and complications were assessed in the Rochester Diabetic Neuropathy Study, a population-based, cross-sectional, and longitudinal epidemiologic survey of 504 patients with diabetes followed for up to 20 years. RESULTS In multivariate analysis, A1C and duration of diabetes (and to a lesser degree age at onset of diabetes but not FPG) were the main significant CGE risk covariates for complications. A derived glycemic exposure index (GE(i)) correlated with and predicted complications better than did individual components. Composite or staged measures of polyneuropathy provided higher correlations and better predictions than did dichotomous measures of whether polyneuropathy was present or not. Generally, the mean GE(i) was significantly higher with increasing stages of severity of complications. CONCLUSIONS A combination of A1C, duration of diabetes, and age at onset of diabetes (a mathematical index, GE(i)) correlates significantly with complications and predicts later complications better than single components of CGE. Serial measures of A1C improved the correlations and predictions. For polyneuropathy, continuous or staged measurements performed better than dichotomous judgments. Even with intensive assessment of CGE and complications over long times, only about one-third of the variability of the severity of complications is explained, emphasizing the role of other putative risk covariates.

Ischemic Stroke Mechanism and Likelihood of Having a Positive Family History of Stroke

P122 Introduction: It is not known whether the magnitude of the inherited component to ischemic stroke risk varies according to presumed mechanism. Differences in familial aggregation of stroke might imply differences in the magnitude of inherited stroke risk. Methods: Probands were eligible for entry into a two-center prospective consecutive patient registry if they presented with an ischemic stroke within 180 days of onset of symptoms. Stroke was defined using WHO criteria. A stroke was considered ischemic if CT or MR imaging done within 7 days of onset of symptoms failed to reveal an alternative diagnosis. Probands were excluded if they had onset of symptoms within 48 hours of a cerebrovascular or cardiovascular proceedure or within 60 days of a nontraumatic subarachnoid hemorhage. Probands were also excluded if they were known to have: CADASIL, Fabry’s disease, homocysteinuria, MELAS, sickle cell disease, mechanical aortic or mitral valve, or biopsy-proven CNS vasculitis. Proband family history was obtained by systematic interview of the proband or next-of-kin. Proband past medical history was obtained by proband interview, record review, or both. A neurologist confirmed the diagnosis of and assigned a TOAST subtype to all index ischemic strokes. A positive family history was defined as a history of stroke in at least one parent or full sibling. Results: We enrolled 283 probands (median age, 75 yrs; male, 52%). Frequencies of TOAST subtypes were: cardioembolic, 17.0% (n=48); large-vessel, 24.7% (n=70); small-vessel, 23.0% (n=65); other, 2.5% (n=7); and unknown, 32.9% (n=93). Frequencies of positive family history by proband ischemic stroke subtype were: cardioembolic, 43.8% (95%CI, 29.5–58.8); large-vessel, 40.0% (95%CI, 28.5–52.4); small-vessel, 47.7% (95%CI, 35.1–60.5); other, 42.9% (95%CI, 9.9–81.6%); and unknown 48.8% (95%CI, 37.9–59.0). Frequencies were not significantly different among subtypes (P=0.718, chi square). Conclusions: The magnitude of inherited risk may not differ dramatically for various clinical subtypes of ischemic stroke. Qualitative differences in inherited stroke risk may exist at the molecular level.

A multivariate generalization of von neumann's ratio

A multivariate generalization, Rv, of von Neumanns ratio is proposed. The null distribution is evaluated under the assumption that observations are independent, identically distributed with a multivariate normal distribution. The Rv statistic provides an intuitively appealing measure of multivariate association which indicates whether the observed serial correlation is positive (the distance between successive observations is less than expected) or negative. The operating characteristics of the corresponding one-sided test is evaluated. A two-sided likelihood ratio test (LR) proposed previously is modified to obtain a one-sided test. Comparisons of these two procedures indicates that both provide accurate control over the size of the test, but that the Rv test appears to be more powerful.