Does Alzheimer's disease with early onset progress faster than with late onset? A case-control study of clinical progression and cerebrospinal fluid biomarkers.

BACKGROUND: Early-onset Alzheimer's disease (EOAD) is generally thought to have a more rapid course compared to late-onset Alzheimer's disease (LOAD). The faster progression of EOAD observed in some studies has also been thought to correlate with cerebrospinal fluid (CSF) biomarkers. Our clinical experience has not been suggestive of any difference in disease progression; therefore, we decided to investigate whether differences in clinical progression and CSF biomarkers between EOAD and LOAD could be demonstrated. METHODS: Case-control study with 42 patients, 21 EOAD and 21 matched LOAD patients. Rates of progression were calculated and these, as well as CSF biomarker levels, were statistically compared. RESULTS: There were no statistically significant differences in clinical progression between the EOAD group and the LOAD group. There was no significant difference in the absolute values of CSF biomarkers, but a tendency towards lower levels of ß-amyloid in patients with EOAD was observed. CONCLUSIONS: Our findings did not converge with results from the majority of previous studies, which have been suggestive of a faster clinical progression in EOAD. Possibly, the very strict algorithm by which our patients were matched explains our findings. However, the findings should be repeated in a larger study population.

Cardiovascular risk factors in men: The role of gonadal steroids and sex hormone-binding globulin.

Males have higher risk of cardiovascular disease (CVD) than premenopausal females. Gonadal steroids are probably involved in the gender difference in CVD, but previous results have been conflicting. We investigated the associations between CVD risk factors and sex hormones in a cross-sectional designed study of 508 healthy males, aged 41 to 72 years. We determined total testosterone (T), sex hormone-binding globulin (SHBG), free androgen index (FAI), and estradiol (E2) and studied their relationship to body fat mass (BF), blood pressure (BP), aortic compliance, left ventricular mass (LVM), and plasma lipids (total cholesterol, high-density lipoprotein [HDL], low-density lipoprotein [LDL], very--low-density lipoprotein [VLDL], and triglycerides). In quartile analyses after adjustment for confounders (age, body mass index [BMI], alcohol consumption, and smoking), SHBG and E2 were positively associated with HDL, while FAI was negatively associated with HDL. T and SHBG were negatively associated with VLDL and triglycerides, while FAI was positively associated with VLDL and triglycerides. T and SHBG were negatively associated with BMI and BF, while FAI and E2 were positively associated with BMI and BF. E2 was negatively associated with LVM. No hormone varied with total cholesterol, LDL, BP, and aortic compliance in the adjusted analyses. In multiple regression analyses, SHBG was the main predictive variable of HDL, VLDL, and triglycerides explaining 12%, 17%, and 17% of the variation, respectively. No other hormones were selected as predictive variables for VLDL and triglycerides, but E2, T, and FAI were selected in the HDL regression, explaining 3%, 2%, and less than 1%, respectively. Our regression analyses illustrate the diverging results when investigating associations between gonadal steroids and lipids with and without SHBG adjustment. Atherogenic lipid profile in males is associated with low SHBG, low T levels, and a high FAI. Males with high E2 levels may have a less atherogenic lipid profile and lower LVM. SHBG is a key hormone in the association between sex hormones and plasma lipids. We suggest that conflicting results of cross-sectional and intervention studies of sex hormones and lipids, in part, may be explained by interindividual differences or changes in SHBG. Thus, further studies on the potential role of SHBG in the development of ischemic heart disease (IHD) should be performed.

Secular and seasonal changes in semen quality among young Danish men: a statistical analysis of semen samples from 1927 donor candidates during 1977-1995.

The objective of this study was to investigate whether semen quality has changed during the years 1977-1995 in a group of unselected semen donor candidates, and to determine whether semen quality is subject to seasonal variation, by analysis of time- and season-related changes in semen quality using multiple regression and ANOVA. The study was based on analysis of the first semen sample delivered by 1927 semen donor candidates in Copenhagen during the period 1977-1995, with determination of semen volume, sperm concentration, total sperm count, percentage motile spermatozoa, and a semiquantitative sperm motility score. Multiple linear regression analysis with year, sexual abstinence and season as covariates showed a significant increase in mean sperm concentration from 53.0 x 10(6)/mL in 1977 to 72.7 x 10(6)/mL in 1995 (p < 0.0001) and in mean total sperm count from 166.0 x 10(6) to 227.6 x 10(6) (p < 0.0001). Mean semen volume and percentage motile spermatozoa did not change. Sperm motility deteriorated, as the spermatozoa in 74.2% of the samples were of excellent motility in 1977-1980 compared to only 41.9% in 1993-1995 (chi 2 = 130.0, p < 0.0001). Analysis of variance showed significant variation between seasons regarding sperm concentration (p < 0.0001) and total sperm count (p < 0.0001). Highest sperm counts were found in spring, with a mean concentration (95% C.I.) of 77.6 x 10(6)/mL (71.9-83.7), and lowest in summer, with a mean of 57.5 x 10(6)/mL (50.1-65.4). No other semen parameter varied with season. It is concluded that sperm counts increased, whereas sperm motility decreased, in a group of Danish semen donor candidates, from 1977 to 1995. Due to the retrospective design and the anonymity of the donors, we were unable to control for variation in donor age, and we cannot exclude the possibility that some donor candidates were selected by being accepted as donors by other semen donor services in Copenhagen. With these limitations in mind, we suggest our results should be interpreted cautiously and regarded as a contribution to the ongoing dispute on whether or not there is a continuous decrease in sperm quality. The seasonal variations found in sperm concentration and total sperm count were pronounced and were not attributable to seasonal differences in the length of sexual abstinence. Additionally, the same seasonal pattern was observed in five successive year-intervals. These findings strongly indicate that human testicular function is influenced by season, a phenomenon well known in many lower mammals.