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In this longitudinal study of 77 patients with mild cognitive impairment (MCI), the authors analyzed whether levels of tau protein phosphorylated at threonine 231 (p-tau(231)) in CSF correlate with progression of cognitive decline. High CSF p-tau(231) levels at baseline, but not total tau protein levels, correlated with cognitive decline and conversion from MCI to AD. Independently, old age and APOE-epsilon 4 carrier status were predictive as well. Our data indicate that an increased p-tau(231) level is a potential risk factor for cognitive decline in patients with MCI.

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The aims of the present study were to compare the current and lifetime prevalences for major and subthreshold affective disorders in elderly subjects in the general population, to assess the influence of demographic variables on prevalence rates, and to examine co-morbidity between these disorders. Major and subthreshold disorders were diagnosed in 286 subjects (aged >/= 60 years). Four-point-nine percent of the subjects had a lifetime diagnosis of major depression, 31.8% either minor or recurrent brief depression, 6.6% a major anxiety disorder, and 18.5% a subthreshold anxiety disorder. The risk for current and lifetime subthreshold anxiety was higher in females than in males, the lifetime prevalence for subthreshold anxiety disorders was increased in elderly subjects and subjects with low professional levels. Increased co-morbidity between major and subthreshold depressive and anxiety disorders could not be observed. In the elderly, subthreshold depressive and anxiety disorders are frequent, more so than major affective disorders. The presence of subthreshold anxiety disorders, but not subthreshold depression, is influenced by age, gender, and previous professional level. Further research focusing on detection, evaluation of risk factors and the relevance for the quality of life in the elderly general population is needed.

Oestrogen therapy has been suggested to have protective effects against Alzheimer's disease. The effects of natural exposure to oestrogen in cognitive disorders have rarely been studied. Assuming that nulliparous women have a higher exposure to natural oestrogen, it could be hypothesised that these women might have a lower risk of Alzheimer's disease than women who have had children. The fertility and number of children in 106 women with a diagnosis of Alzheimer's disease was examined and compared with that of 189 female subjects from two control groups with subjects without dementia. As additional control, the same comparisons were carried out for 40 male patients with Alzheimer's disease and 105 male control subjects. In female subjects, having had children was found to be associated with a diagnosis of Alzheimer's disease. This was not the case in male subjects. The number of children did not seem to affect the risk of Alzheimer's disease, neither in female nor in male subjects. Natural exposure to oestrogen seems to reduce the risk of Alzheimer's disease in women.

Alzheimer's disease (AD) patients often present with concurrent major depression (MD). To investigate the reasons for this comorbidity, e.g. MD being a risk factor for AD, or both diagnoses having a common neurobiology, the temporal relationship between the first onset of AD and of MD during lifetime was investigated-57 out of 146 AD patients had a lifetime diagnosis of MD. The correlation between the ages at onset of MD and dementia was calculated. The incidence of MD in AD patients in several 5-year-intervals before and after the onset of AD was compared with the average incidence of MD in the present AD sample and with the expected incidence of MD in the general population. No significant correlation between the onset of AD and of MD could be found after controlling for age, gender and the Mini-Mental-State. However, the incidence of MD 5 years before and after the onset of AD significantly exceeded the expected incidences-MD is only partially related to AD. However, the increased incidence of MD within 5 years before and after the onset of dementia may indicate that a common neurobiological process causes cognitive decline and depression in a subsample of AD patients.

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The peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a member of the steroid hormone super family of ligand-inducible transcription factors, involved in glucose and lipid metabolism. We screened for polymorphisms in the PPAR-alpha gene and detected two known polymorphisms located in exon 5 and intron 7. These polymorphisms were investigated for their possible association with Alzheimer's disease (AD) and for their effect in carriers of an insulin gene (INS) polymorphism. The PPAR-alpha C --> G polymorphism in exon 5 (L162V) was associated with AD, in that the V-allele was more frequent in AD patients than in healthy subjects. Further data analysis revealed that carriers of an PPAR-alpha L162V V-allele and an INS-1 allele presented with an increased risk for AD. Cerebrospinal fluid amyloid-beta levels were influenced by PPAR-alpha L162V genotype. These results suggest, that PPAR-alpha polymorphism may be a risk factor for AD.