Hair loss,insulin resistance,and heredity in middle-aged women. A population-based study

CONTEXT: The association of androgenic alopecia (AGA) with insulin resistance, coronary artery disease and hypercholesterolemia has been previously reported in men, but no such association has been reported in women with female androgenic alopecia (AGA). Female AGA has usually been linked with hyper-androgenism and hirsutism and, most recently, also with polycystic ovarian syndrome (PCOS), even though epidemiological documentation of the latter association is scanty. Polycystic ovarian syndrome is quite common among Caucasian women, and its association with insulin resistance is well documented. OBJECTIVES AND DESIGN: The aim of this study was to obtain a more precise estimation of the prevalence on female AGA and to describe its possible connections with insulin resistance linked parameters and with paternal and maternal family history of alopecia. A cross-sectional population based cohort survey was carried out in the City of Oulu, Finland in 1998. SETTING AND PARTICIPANTS: As a part of a population based cohort study the hair status of 324 women aged 63 years was assessed by a modification of Ludwig's scale. The background data consisting of anthropometric measures (weight, height, body mass index, waist, hip and neck circumferences), smoking status, chronic diseases and their medication as well as the family history of AGA were collected by questionnaires and interviews made by study nurses and in clinical examination. Blood samples for laboratory tests were taken on the same occasion. RESULTS: The prevalence of extensive loss of hair (at least grade II or III on Ludwig's scale) was quite high (31.2%). The insulin resistance associated parameters, such as waist and neck circumferences, abdominal obesity measured by waist-to-hip ratio, mean insulin concentration (11.3 mU/l versus 9.95 mU/l, p=0.02) or urinary albumin-to-creatinine ratio (1.80 versus 1.58, p=0.01), were significantly higher in women with extensive hair loss compared to those with normal hair or only minimal hair loss (grade I on Ludwig's scale). The women belonging to the highest quintiles of neck or waist circumferences had significantly increased risk for extensive hair loss compared to those with normal hair or minimal hair loss, the unadjusted ORs being 2.25 (95% CI, 1.26-4.03) and 1.75 (95% CI, 1.00-3.07), respectively. Similarly in women with hyperinsulinemia (fs-insulin >10 mU/l), microalbuminuria (urinary albumin-to-creatinine ratio exceeding the highest microalbuminuria decile (>2.5 mg/mmol) and paternal history of AGA the ORs for alopecia were increased being 1.65 (95% CI, 1.02-2.67), 2.39 (95% CI, 1.21-4.73) and 2.08 (95% CI, 1.26-3.44). All of these ORs, except those for highest quintiles of waist and neck circumferences remained significant in multiple adjusted models. CONCLUSIONS: According to the results of this study, female AGA (grade II or III on Ludwig's scale) was quite common among Finnish women aged 63 years. Our results support the hypothesis that women with some markers of insulin resistance have significantly increased risk for female AGA. Paternal history of alopecia seemed to be more common in female AGA compared to women with normal or minimal loss of hair.     

Interleukin 1 alpha gene polymorphism as a susceptibility factor in Alzheimer's disease and its influence on the extent of histopathological hallmark lesions of Alzheimer's disease

We investigated the association of the interleukin 1alpha (IL1A) (-889) C/T polymorphism with Alzheimer's disease (AD) and with the extent of AD histopathological lesions, the senile/neuritic plaques (SPs/NPs) and neurofibrillary tangles. We evaluated 98 neuropathologically confirmed AD patients and 240 controls as well as 146 clinically diagnosed AD patients and 278 controls but found no association of the IL1A C/T polymorphism with AD even after adjustment for the apolipoprotein E (APOE) genotype, gender or age. The extents of AD histopathological lesions were not influenced by the IL1A genotype except after exclusion of the APOE epsilon4 allele, when a trend towards more SPs/NPs was observed in AD patients with the IL1A C/C compared to patients with the T/T genotype. These results do not confirm previous studies which have indicated that the IL1A C/T polymorphism is a susceptibility factor for AD. However, the IL1A C/C genotype might be associated with the progression of SPs/NPs in AD patients, but the effect is weak and obscured by the APOE epsilon4 allele.     

Clinical characteristics of frontotemporal patients with symmetric brain atrophy

In this paper we explored patterns of frontal and temporal asymmetry in frontotemporal dementia (FTD) and tried to isolate clinical correlates associated with asymmetry or lack thereof. Volumes of frontal and temporal lobes, hippocampus and entorhinal cortex were measured using magnetic resonance imaging (MRI) in 10 patients with FTD. Age- and cranial size-specific values were computed through linear regression analysis (W-scores). A subgroup of 3 patients with symmetric frontal and temporal atrophy was identified. When compared to patients with asymmetric atrophy, the former had younger age at onset of the disease (p = 0.02), greater overall frontotemporal (p = 0.02) and greater entorhinal atrophy (p < 0.04). Two of the three patients were apolipoprotein E ɛ4 carriers versus none of the asymmetric patients (p = 0.02). The lack of asymmetry in this small sample of FTD patients was associated with greater brain atrophy, younger age at onset, and presence of the ɛ4 allele of apolipoprotein E. The presence of the ɛ4 allele is consistent with the hypothesis of greater vulnerability of the brain in ɛ4 carriers. Received: 15 April 2002 / Accepted: 2 October 2002 Correspondence to Dr. G. B. Frisoni     

Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease

OBJECTIVES: To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS: This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS: Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS: Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.     

Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance

The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3'-untranslated region (3'UTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3'UTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p = 0.747). However, the insertion allele was associated with a significant reduction in weight (p = 0.016), BMI (p = 0.009), and waist circumference (p = 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p = 0.036), whereas men lost more weight and had a greater decrease in BMI. The pentanucleotide insertion/deletion polymorphism in the 3'UTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.     

The common polymorphisms (single nucleotide polymorphism [SNP] +45 and SNP +276) of the adiponectin gene predict the conversion from impaired glucose tolerance to type 2 diabetes: the STOP-NIDDM trial

Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and antiatherogenic properties. Therefore, the adiponectin gene is a promising candidate gene for type 2 diabetes. We investigated the single nucleotide polymorphisms (SNPs) +45T/G and +276G/T of the adiponectin gene as predictors for the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial, which aimed to investigate the effect of acarbose compared with placebo on the prevention of type 2 diabetes. Compared with the TT genotype, the G-allele of SNP +45 was associated with a 1.8-fold risk for type 2 diabetes (95% CI 1.12-3.00, P = 0.015) in the placebo group. Subjects treated with placebo and simultaneously having the G-allele of SNP +45 and the T-allele of SNP +276 (the risk genotype combination) had a 4.5-fold (1.78-11.3, P = 0.001) higher risk of developing type 2 diabetes compared with subjects carrying neither of these alleles. Women carrying the risk genotype combination had an especially high risk of conversion to diabetes (odds ratio 22.2, 95% CI 2.7-183.3, P = 0.004). In conclusion, the G-allele of SNP +45 is a predictor for the conversion to type 2 diabetes. Furthermore, the combined effect of SNP +45 and SNP +276 on the development of type 2 diabetes was stronger than that of each SNP alone.     

Visual assessment of medial temporal atrophy on MR films in Alzheimer's disease: comparison with volumetry

BACKGROUND AND AIMS: To test the agreement of a visual rating scale of medial temporal lobe atrophy (MTA) with linear and volumetric assessments, and to test its accuracy in discriminating between Alzheimer's disease (AD) patients and controls. METHODS: Participants were 28 patients with AD and 29 healthy controls. MTA was evaluated according to Scheltens' five-point scale. Its accuracy in distinguishing AD patients from controls was evaluated as a stand-alone measure and in association with linear [width of the temporal horn (WTH)] and volumetric [hippocampal volume (HV)] measures. RESULTS: The agreement of this visual rating scale with the other MTA measures was statistically significant (vs WTH and vs HV, p for trend < 0.00005). The visual rating scale showed a good accuracy in distinguishing AD patients from controls [area under the curve (AUC) 0.89, 95% confidence interval (CI) 0.79-0.98]. Although the accuracy of the visual rating scale improved in association with linear WTH (AUC 0.91, 95% CI 0.82-0.99) and in association with HV (AUC 0.93, 95% CI 0.86-1.00), the improvement was not significant. CONCLUSIONS: The visual rating scale of MTA, easily applicable in clinical practice, shows good agreement with more demanding quantitative methods, and can discriminate AD patients from controls with good accuracy.     

A voxel based morphometry study on mild cognitive impairment

BACKGROUND: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. OBJECTIVE: To study the pattern of brain atrophy in MCI. METHODS: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p < 0.001. RESULTS: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere-for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. CONCLUSIONS: The MRI findings in MCI resemble those seen in early AD.