Mild cognitive impairment: believe it or not?

Mild cognitive impairment (MCI) was previously defined as a transitional state that can precede dementia, but the condition and the rates of conversion remain controversial. MCI is now the focus of natural history studies, along with Alzheimer's disease (AD) prevention. The objective of our review will be to consider the question of whether MCI is a well enough established entity that it can be a diagnosis in medical practice and a valid target of Alzheimer's prevention therapy. MCI was originally defined by Petersen et al. (1999) as progressive memory loss, prodrome of Alzheimer's disease. More recently MCI has been expanded to other cognitive domains with other potential causes like normal aging, fronto-temporal dementia, and vascular dementia. Despite many consensus conferences, experts cannot agree on critical aspects of the MCI, particularly with respect to its clinical utility. Based on neuropsychological studies, a hippocampal memory profile has been proposed for MCI as prodromal AD. Further research is needed to advance these criteria. We have no doubt, however, that in the future, the diagnosis of AD as disease (not only a dementia syndrome) will be made in the early pre-dementia stage and will be drawn from a combination of neuropsychological, neuro-imaging and CSF biomarkers.

Alteration of the vascular endothelial growth factor and angiopoietins-1 and -2 pathways in transitional cell carcinomas of the urinary bladder associated with tumor progression.

Neoangiogenesis is assumed to play an important role in the progression, metastasis and prognosis of a wide variety of tumors. To get insights into the molecular-genetic pathways and the biological role of angiogenesis in urothelial carcinogenesis, we analyzed comparatively the expression of the mRNA of the vascular endothelial growth factor (VEGF) and of the angiopoietins-1 and -2 (Ang-1 and Ang-2) in 71 transitional cell carcinomas (TCC) of the urinary bladder in relation to the tumor grades and stages, and referring to epidemiological risk factors. Using real-time quantitative reverse transcription-polymerase chain reaction, low-stage superficial TCC expressed VEGF and Ang-2 mRNA at a significantly higher level than high-stage muscle invasive carcinomas, and low-grade TCC at an insignificantly higher level than high-grade tumors. The activity of both angiogenic factors was found to be significantly correlated. Conversely, Ang-1 mRNA was expressed at a 3-fold significantly lower level in low-grade, low-stage compared to high-grade, high-stage TCC. A significantly 3- and 2-fold respectively, drop of the VEGF and Ang-2 mRNA expression in conjunction with a 2-fold significantly higher expression of Ang-1 mRNA in the group of grade 2 TCC when infiltrating the muscle layer may represent a crucial event during urothelial carcinogenesis, and possibly indicates an important step in promoting the conversion of bladder cancer from a low to a high malignancy in this subset of carcinomas. By immunhistochemistry, high-grade, high-stage carcinomas less frequently displayed areas with a strong reactivity for the VEGF protein ('hot spots") than low-grade, low-stage TCC, paralleling the expression of the mRNA. The expression patterns observed are compatible with a reduced vascular destabilization and decreased formation of new blood vessels in advanced TCC, suggesting a balance between vessel regression and vascular growth, with a less pronounced vascular remodeling during late phases of urothelial carcinogenesis. Analyzing the effect of life-style bladder cancer risk factors, habitual smoking and coffee consumption was not observed to substantially alter the expression of the angiogenic mediators, except for weakly elevated levels of VEGF and Ang-2 mRNA in TCC of strong smokers and a borderline significantly decreased VEGF mRNA expression associated with heavy coffee consumption. Certain hazardous occupational exposures (polycyclic hydrocarbons, paints and lacquer, stone dust) may play a role in modulating tumor angiogenesis. The current data indicate that the signaling molecular-genetic pathways underlying vascular remodeling are involved in the progression of urinary bladder cancer to a more malignant and aggressive behaviour.

Late- versus early-onset geriatric depression in a memory research center.

OBJECTIVE: To contrast early-onset (<60 years) and late-onset (>60 years) depression in geriatric patients by evaluating differences in cognition, vascular comorbidity and sociological risk factors. Both patient groups were compared with normal subjects. MATERIALS AND METHODS: We recruited 76 patients with depressive symptoms (37 late onset and 39 early onset) and 17 normal controls matched by age and educational level. All subjects were assessed using a semistructured neuropsychiatric interview and an extensive neuropsychological battery. Vascular and sociological risk factors were also evaluated. RESULTS: We found a significant variation in performance between depressive patients and normal controls in most cognitive functions, especially memory (P < 0.0001), semantic fluency (P < 0.0001), verbal fluency, and digit-symbol (P < 0.0001). Late-onset depression patients scored lower and exhibited more severe impairment in memory domains than early-onset depression patients (P < 0.05). Cholesterol levels and marital status were significantly (P < 0.05) different between the depressive groups. Both depressed groups (early- and late-onset) were more inactive than controls (P < 0.05; odds ratio: 6.02). CONCLUSION: Geriatric depression may be a manifestation of brain degeneration, and the initial symptom of a dementia. It is important to consider this in the treatment of patients that exhibit late-onset depressive symptoms.