Mitochondrial DNA haplogroups and APOE4 allele are non-independent variables in sporadic Alzheimer's disease.

Allele epsilon4 of the nuclear APOE gene is a leading genetic risk factor for sporadic Alzheimer's disease (AD). Moreover, an allele-specific effect of APOE isoforms on neuronal cell oxidative death is known. Because of the role of the mitochondrial genome (mtDNA) in oxidative phosphorylation and oxidative stress, an interaction between APOE polymorphism and mtDNA inherited variability in the genetic susceptibility to sporadic AD can be hypothesized. We have explored this hypothesis by analyzing mtDNA germline variants (mtDNA haplogroups) in a sample of AD patients (213 subjects) genotyped for APOE and classified as APOE epsilon4 carriers and non-carriers. We found that the frequency distribution of mtDNA haplogroups is different between epsilon4 carriers and non-carriers (P=0.018), thus showing non-random association between APOE and mtDNA polymorphisms. The same analysis, carried out in two samples of healthy subjects (179 age-matched and 210 individuals aged more than 100 years), showed independence between epsilon4 allele and mtDNA haplogroups. Therefore, the APOE/mtDNA interaction is restricted to AD and may affect susceptibility to the disease. In particular, some mtDNA haplogroups (K and U) seem to neutralize the harmful effect of the APOE epsilon4 allele, lowering the epsilon4 odds ratio from statistically significant to non-significant values.

Serum magnesium levels and cognitive impairment in hospitalized hypertensive patients.

We performed this cross-sectional case control study to investigate the association between low serum magnesium levels and cognitive impairment in hypertensive hospitalized patients. The study was carried out in general medical care units at 81 hospitals participating in the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study throughout Italy, and a total of 1058 patients with diagnoses of hypertension at the discharge were studied. The occurrence of cognitive impairment at discharge was the primary outcome of our study. Cognitive impairment was ascertained using the Hodkinson Abbreviated Mental Test (HAMT). Sociodemographic variables, body mass index, laboratory parameters, comorbidity, use of antihypertensive drugs and number of drugs were considered as potential confounders. Twenty-nine percent of the selected hypertensive patients were classified as having cognitive impairment. In univariate analysis, older age, female sex, and low educational level showed a significant trend for association to cognitive impairment. Moreover the proportion of subjects with cognitive impairment decreased with increasing alcohol consumption, and the prevalence of ex smokers and smokers was significantly lower in patients with cognitive impairment. The lower tertiles for serum albumin and creatinine clearance were more frequent among patients with cognitive impairment, and the lower tertile for serum magnesium levels was significantly more frequent in these patients. Number of drugs was slightly lower in cognitively impaired patients, while number of diagnoses and length of hospital stay were higher in these subjects. In the multivariate logistic regression analysis cognitive impairment decreased with increasing education level (highest education: OR 0.11; 95 per cent CI 0.05-0.25). The lower tertile for serum albumin (< 3.5 g/dl) was significantly associated to cognitive impairment (OR 2.14; 95 per cent CI 1.31-3.49), as well as the lower tertiles for serum magnesium (0.74-0.86 mmol/L: OR 1.54; 95 per cent CI 1.06-2.22; < 0.74 mmol/L: OR 1.75; 95 per cent CI 1.13-2.72]. Our results demonstrate the existence of a significant association between magnesium imbalance and cognitive impairment. These data suggest that the assessment of magnesium status may be of some relevance in hypertensive subjects with cognitive disorders.

Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2).

The possibility that four loci (REN, THO, PARP, SOD2) are associated with longevity was explored by comparing the genotypic pools of subjects older than 100 years with those of younger subjects matched for sex and geographic area (northern and southern Italy). The markers (all located within the respective gene) were HUMREN4; HUMTHO1; HUMPARP (gt)845nt; SOD2(C/T)401nt. In order to reduce the number of genotypes, multiallelic polymorphisms were recoded as diallelic according to allele size and frequency patterns (small: S, and large: L, alleles). A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls. On the other hand no significant difference was found between case/control genotypic frequencies at REN, PARP, SOD2 loci. The latter loci therefore do not affect inter-individual variability in life expectancy (at least in terms of qualitative variants associated with the tested markers). However, the data is consistent with an association between the THO locus and longevity.

[Cancer in the elderly. Clinico-epidemiologic considerations]. / Il cancro negli anziani. Considerazioni clinico-epidemiologiche.

The elderly population is rapidly increasing in Western countries. Old age indirectly represents one of the most important risk factors for the development of neoplasias. In Italy in 1991 a total of 14,572 deaths from tumours were recorded, equivalent to 27% of all deaths; of these over 66% affected individuals aged over 65 years old. In the 65-74 age bracket mortality caused by tumour is the prime cause of death in Italy and is undergoing an exponential increase over time. The most frequently found tumours and above all the cause of the greatest number of deaths in the elderly population are lung cancer, prostate cancer, breast cancer, colorectal cancer, stomach cancer. To date the only weapon that has proved efficacious in some tumours (breast, colon-rectal, prostate, melanoma) is early diagnosis through screening and adequate treatment. The elderly are an extremely heterogeneous population and it is therefore not easy to provide guidelines that are applicable to the entire population. Firstly, it is important to provide more information in order to permit effective and targeted prevention. In order to fulfil this objective, structures offering the necessary equipment and skills will have to be create; training must be provided for personnel in this type of preventive medicine; lastly, the awareness of doctors towards this type of medicine must be increased by providing the correct information.