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Distinguishing amnestic mild cognitive impairment (MCI) from Alzheimer's disease (AD) and healthy aging depends mainly on clinical evaluation, and, ultimately, on investigator's judgment. Clinical evaluation in vivo is based primarily on cognitive assessments. The present study explores the potential of volumetric magnetic resonance imaging of parietal and lateral temporal brain structures to support the diagnosis of AD and to distinguish AD patients from patients with MCI and healthy control subjects (HCS). 52 age-matched HCS, 18 patients with MCI, and 59 patients with probable late onset AD were investigated. Using computational, neuromorphometric procedures gray matter (GM) was automatically parcellated into 28 local regions of interest, the volumes of which were computed. The left hippocampus (sensitivity/specificity: 80.8-90.4%/55.6-86.4%) and the right hippocampus (73.1-90.4%/66.7-84.7%) provided highest diagnostic accuracy in separating all three diagnostic groups. Promising diagnostic values for distinguishing MCI from HCS were found for the left superior parietal gyrus (61.5%/55.6%) and left supramarginal gyrus (65.4%/66.7%), and for distinguishing subjects with MCI from AD patients for the right middle temporal gyrus (77.8%/79.7%), left inferior temporal gyrus (83.3%/72.9%), and right superior temporal gyrus (77.8%/71.2%). The left superior temporal pole (92.3%/84.7%), left parahippocampal gyrus (86.5%/81.4%), left Heschl's gyrus (86.5%/79.7%), and the right superior temporal pole (82.7%/78.0%) revealed most promising diagnostic values for distinguishing AD patients from HCS. Data revealed that lateral temporal and parietal GM volumes distinguish between HCS, MCI, and AD as accurate as hippocampal volumes do; hence, these volumes can be used in the diagnostic procedure. Results also suggest that cognitive functions associated with these brain regions, e.g., language and visuospatial abilities, may be tested more extensively to obtain additional information that might enhance the diagnostic accuracy further. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a devastating neurodegenerative disease that affects more than 15 million people worldwide. Within the next generation, these numbers will more than double. To assist in the elucidation of pathogenic mechanisms of AD and related disorders, such as frontotemporal dementia (FTDP-17), genetically modified mice, flies, fish and worms were developed, which reproduce aspects of the human histopathology, such as ß-amyloid-containing plaques and tau-containing neurofibrillary tangles (NFT). In mice, the tau pathology caused selective behavioral impairment, depending on the distribution of the tau aggregates in the brain. ß-Amyloid induced an increase in the numbers of NFT, whereas the opposite was not observed in mice. In ß-amyloid-producing transgenic mice, memory impairment was associated with increased levels of ß-amyloid. Active and passive ß-amyloid-directed immunization caused the removal of ß-amyloid plaques and restored memory functions. These findings have since been translated to human therapy. This review aims to discuss the suitability and limitations of the various animal models and their contribution to an understanding of the pathophysiology of AD and related disorders.Molecular Psychiatry (2004) 9, 664-683. doi:10.1038/sj.mp.4001508 Published online 30 March 2004 [ABSTRACT FROM AUTHOR]

A common polymorphism of the gene encoding acyl-coenzyme A: cholesterol acyltransferase 1 (SOAT1), which is involved in the regulation of β-amyloid peptide generation, is associated with low brain amyloid load (P = 0.03) and with low cerebrospinal fluid levels of cholesterol (P = 0.005). This polymorphism of SOAT1 is also associated with reduced risk for Alzheimer's disease in ethnically distinct populations (P = 0.0001, odds ratio: 0.6, 95% confidence interval 0.4-0.8). [ABSTRACT FROM AUTHOR]

Background: The deposition of tau protein in neurofibrillary tangles constitutes an important feature of many neurodegenerative disorders, including Alzheimer's disease. A polymorphic gene, saitohin (STH), nested within the tau gene (microtubule associated protein tau, MAPT), was recently identified and an association of a non-synonymous polymorphism in STH with increased risk for Alzheimer's disease was suggested.Objective and Methods: To test the above hypothesis in a case-control association study of two independent white populations within Switzerland and Greece, comparing genotype and allele frequencies from 225 Alzheimer's disease patients and 144 healthy control subjects.Results: No differences in allelic or genotypic distributions between Alzheimer's disease patients and controls was found in the individual samples (Swiss/Greek) or in the combined sample. Stratification for the presence of apolipoprotein E (APOE) epsilon 4 allele, sex, or age did not show significant effects in the populations studied, nor was there an effect on the age of onset.Conclusions: No evidence was found for an association of the non-synonymous polymorphism (Q7R) in STH and Alzheimer's disease. This finding is in line with earlier studies showing no association between MAPT and Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background and purpose The neuropathological process starts years before the diagnosis of Parkinson's disease ( PD). Assessment of prodromal features in healthy individuals may help to define those with high risk for future PD. Our aim was to evaluate the presence and progression of prodromal markers in individuals with low risk [healthy controls ( HC), n = 14] and high risk for PD ( HR- PD, n = 34) and early PD ( n = 14) patients. Methods Several risk or prodromal markers were combined to define HR- PD. Other prodromal markers were followed in 6-month intervals for 2 years. As recommended by the Movement Disorder Society Task Force, likelihood ratios ( LRs) of markers, motor scores and PD probability scores were calculated and compared. Results The baseline LR for non-motor prodromal markers was significantly higher in PD and HR- PD compared to HC. Within 2 years, changes in these LRs did not significantly differ between the groups. Motor worsening was significant only in the PD group (50% of the patients) against HR- PD (15%) and HC (7%). Change in the non-motor prodromal LR did not significantly correlate with motor worsening, but higher baseline non-motor LRs were associated with Unified Parkinson's Disease Rating Scale III values at 2 years of follow-up. Conclusions Our study shows that the frequency of non-motor prodromal markers is higher in the HR- PD group but does not increase within 2 years. The progression of motor and non-motor markers seems to be independent, but higher baseline non-motor burden is associated with the motor status after 2 years. Moreover, our data argue for a high impact of motor markers in the risk estimation for future PD. [ABSTRACT FROM AUTHOR]

Rationale: Cognitive symptoms have increasingly been recognized as an important target in the development of future treatment strategies in schizophrenia. The nicotinergic neurotransmission system has been suggested as a potentially interesting treatment target for these cognitive deficits. However, previous research yielded conflicting results, which may be explained by several methodological limitations, such as the failure to include both a group of smoking and non-smoking schizophrenic patients, the use of only a single nicotine dose, and the inclusion of a very limited cognitive battery. Objectives: The present study aims at investigating the cognitive effects of nicotine in schizophrenia while addressing these methodological issues. Methods: In a double-blind placebo-controlled randomized crossover design, cognitive effects are assessed in smoking ( n = 16) and non-smoking ( n = 16) schizophrenic patients after receiving active (1 or 2 mg) or placebo oromucosal nicotine spray. Results: A modest improving effect of nicotine on attention in the smoking but not the non-smoking group was found. No enhancing effects were found on measures of visual memory, working memory, processing speed, psychomotor speed, or social cognitive functioning in either patient group. Conclusions: These findings suggest that the nicotinic receptor only has limited value as a cognitive treatment target in schizophrenia. [ABSTRACT FROM AUTHOR]