Modifiable vascular risk factors, white matter disease and cognition in early Parkinson's disease.

BACKGROUND AND PURPOSE: Dementia in Parkinson's disease (PD) is common and disabling. Identification of modifiable risk factors for it is essential. Vascular risk factors (VRFs) may be associated with cognitive decline in early PD. Biomarkers that serve as surrogates of the long-term effect of VRFs on PD are needed. To that end, we aimed to quantitate white matter hyperintensities (WMH) in early PD, measure associations with VRFs and examine relationships between WMH and longitudinal cognition. METHODS: Participants in the Parkinson's Progression Markers Initiative study (141 patients with PD, 63 healthy controls) with adequate baseline structural brain magnetic resonance imaging data were included. Hypertension and diabetes history, and body mass index were combined to create a vascular risk score. WMH were quantitated via automated methods. Cognition was assessed annually with a comprehensive test battery. RESULTS: In the PD group, vascular risk score was associated with WMH for total brain (ß = 0.210; P = 0.021), total white matter (ß = 0.214; P = 0.013), frontal (ß = 0.220; P = 0.002) and temporal (ß = 0.212; P = 0.002) regions. Annual rate of change in global cognition was greater in those with higher vascular risk score (ß = -0.040; P = 0.007) and greater WMH (ß = -0.029; P = 0.049). Higher temporal WMH burden was associated with great decline over time in verbal memory (ß = -0.034; P = 0.031). CONCLUSIONS: In early PD, modifiable VRFs are associated with WMH on brain magnetic resonance imaging. Temporal WMH burden predicts decline in verbal memory. WMH may serve as a surrogate marker for the effect of VRFs on cognitive abilities in PD.

Longitudinal changes in cognition in early Parkinson's disease patients with REM sleep behavior disorder.

INTRODUCTION: Cognitive decline is common in Parkinson's disease (PD), and identifying patients at highest risk for it is essential. We aimed to examine the effect of possible REM sleep behavior disorder (pRBD) on rate of cognitive decline in early PD, for both global cognition and in specific cognitive domains. METHODS: Parkinson's Progression Markers Initiative (PPMI) is a multi-site, international study of PD patients untreated at enrollment. pRBD was assessed with the REM sleep behavior disorder questionnaire (RBDSQ). Global cognition was assessed at baseline and annually using the Montreal Cognitive Assessment (MoCA) and a cognitive battery. Linear mixed effects models were used to examine the relationship between pRBD (RBDSQ≥6) and rate of change in cognitive variables. Age, sex, years of education, and baseline motor and cognitive scores were included as covariates. RESULTS: The baseline sample consisted of 423 individuals with PD, mean age 61.7 years and 65.5% male. Data was available on 389, 366, and 196 participants at 1-year, 2-year, and 3-year follow-up respectively. Possible RBD occurred in 108 (25.5%) at baseline. In multivariate analyses, baseline RBD was associated with greater annual rate of decline in MoCA score (ß = -0.34, 95%CI -0.54, -0.13, p < 0.001), Symbol Digit Modalities Test (ß = -0.69, 95%CI -1.3, -0.09, p = 0.024), and Hopkins Verbal Learning Test-Revised, delayed free recall (ß = -0.21, 95%CI -0.41, -0.013, p = 0.037). CONCLUSIONS: Possible RBD is common in early PD and predicts future cognitive decline, particularly in attention and memory domains.

[Diabetes of idiopathic haemochromatosis and common diabetes mellitus. Results of a prospective study of 97 families with idiopathic haemochromatosis (author's transl)]. / Diatete de l'hémochromatose idiopathique et diabéte commun. Résultats d'une étude prospective de 97 familles d'hémochromatose idiopathique

The purpose of this study was to investigate through an epidemiological approach two controversial aspects of the pathogenesis of the diabetes mellitus of idiopathic haemochromatosis (I.H.) : the possible inheritance of the gene(s) for common diabetes mellitus (C.D.), and the diabetogenic role of iron overload. More than 80% of the living first degree relatives of 97 patients with I.H. were examined, while data were collected by inquiry concerning first degree relatives who had refused investigations or had died. Data on the more distant family members were also collected by inquiry. Physical examination and estimation of serum iron level and unsaturated-iron-binding capacity were systematically performed. When an anomaly had been thus detected further investigation for iron overload was carried out by mean of a deferoxamine test and eventually by liver biopsy. Evaluation of carbohydrate metabolism included testing for post-prandial glycosuria, estimation of post-prandial blood sugar, and eventually an oral glucose tolerance test. The results were compared to those of an inquiry for family history of diabetes in 100 patients with C.D. successively admitted to our department. Among the first degree relatives of patients with C.D. the prevalence of overt diabetes was 33 of 612 (5.4 %); whereas in the I.H. group it was 8 of 735 (1.1 %). The differences between the C.D. and I.H. groups were significant, whether the total I.H. group (p less than 10(-5)) or only I.H. proposite having overt diabetes (p less than 2 X 10(-2)) were considered. With respect to the more distant relatives the number of affected families was significantly higher in the C.D. group (31 of 100) than in the total I.H. group (5 of 97 ; p less than 10(-5)) or in the I.H. sub-group diabetic proposite (3 of 36 ; p less than 10(-2)). The frequency of carbohydrate intolerance in relatives bore no relation to the carbohydrate pattern of propositi. Carbohydrate intolerance was frequently found in relatives with iron overload (17 of 72). However, no correlation was observed between blood sugar and serum iron level or unsaturated-iron-binding-capacity, relatively gross parameters. Thus, the pathogenesis of diabetes mellitus associated with I.H. remains uncertain, but the inheritance of gene(s) for common diabetes is unlikely to play a determinant role.

Heredity of idiopathic haemochromatosis: a study of 106 families.

More than 80% of the first degree relatives of 106 patients with iron overload - 97 with idiopathic haemochromatosis (I.H.) and nine with haemosiderosis secondary to alcohol induced liver disease (A.H. - were examined. Physical examination and measurement of plasma iron level and UIBC were done in all subjects; relatives who presented with some anomaly were submitted to a desferrioxamine test and, if the latter showed a high urinary iron output, to a liver biopsy. While absent in relatives of A.H. patients, iron overload was present in 78 out of 499 relatives of I.H. patients: 29 major and 49 minor forms. The major forms involved the sibships almost exclusively. The genetic analysis showed much evidence in favour of a recessive or rather intermediate form of inheritance, with heterozygous developing minor forms. However, other modes of transmission, especially polygenic (probably oligogenic), cannot be totally excluded. Data from recent studies showing a strong correlation between I.H. and certain HLA antigens do not conflict with the above conclusions.