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In this study, we analyzed differences in cortical thickness (CTH) between healthy controls (HC), subjects with stable mild cognitive impairment (S-MCI), progressive MCI (P-MCI), and Alzheimer's disease (AD), and assessed correlations between CHT and clinical disease severity, education, and apolipoprotein E4 (APOE) genotype. Automated CTH analysis was applied to baseline high-resolution structural MR images of 145 subjects with a maximum followup time of 7.4 years pooled from population-based study databases held in the University of Kuopio. Statistical differences in CTH between study groups and significant correlations between CTH and clinical and demographic factors were assessed and displayed on a cortical surface model. Compared to HC group (n = 26), the AD (n = 21) group displayed significantly reduced CTH in several areas of frontal and temporal cortices of the right hemisphere. Higher education and lower MMSE scores were correlated with reduced CTH in the AD group, whereas no significant correlation was found between CDR-SB scores or APOE genotype and CTH. The P-MCI group demonstrated significantly reduced CTH compared to S-MCI in frontal, temporal and parietal cortices even after statistically adjusting for all confounding variables. Ultimately, analysis of CTH can be used to detect cortical thinning in subjects with progressive MCI several years before conversion and clinical diagnosis of AD dementia, irrespective of their cognitive performance, education level, or APOE genotype. [ABSTRACT FROM AUTHOR]

Background: In mild cognitive impairment (MCI), Alzheimer’s disease (AD)-type cerebrospinal fluid (CSF) biomarker profiles predict rapid progression and conversion to AD. An increased brain amyloid burden in AD and MCI has been demonstrated with PET using [11C]PIB (Pittsburgh compound B). Little is known about the relationship between these biomarkers in MCI. Methods: We studied 15 patients with amnestic MCI and 22 controls with PET using [11C]PIB. In MCI patients, CSF levels of Aβ42, pTAU, totalTAU and the Aβ42/pTAU ratio were measured. Results: In MCI patients, CSF Aβ42 was abnormal in 53% of patients, totalTAU in 67%, pTAU in 64% and the Aβ42/pTAU ratio in 64%. A composite neocortical [11C]PIB uptake score was increased in 87% of the MCI patients. Only 54% of [11C]PIB-positive subjects showed AD-type Aβ42 values. During a 2-year follow-up, 6 MCI patients converted to AD, all of them had increased neocortical PIB scores at the MCI stage. Abnormal CSF Aβ42 was found in 3 patients, pTAU in 3 patients and Aβ42/pTAU ratio in 4 patients. Conclusion: Follow-up studies are needed to confirm whether [11C]PIB uptake might be more sensitive than CSF Aβ42 concentration in detecting increased amyloid burden in MCI, as suggested by the results of this study. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimer’s disease. Earlier studies have shown differences in brain structure according to the APOE ε4 status. Objective: To assess possible differences in brain structure according to the APOE ε4 status in mild cognitive impairment (MCI) subjects in relation to conversion to dementia. Methods: In a follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI) during a mean follow-up time of 31 months. Brain structure differences in both stable MCI (SMCI) and PMCI ε4 carriers and noncarriers in the baseline MRI scan were assessed with voxel-based morphometry. Results: The SMCI ε4 carriers had atrophy in the amygdala and hippocampus compared to the SMCI noncarriers. The PMCI ε4 carriers revealed atrophy of the left inferior frontal gyrus and parietal cortex compared to the PMCI noncarriers. Conclusion: The rate of brain atrophy in certain brain areas may be increased in ε4-positive MCI subjects progressing to dementia. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Summary. Apolipoprotein E (ApoE) genotype has been shown to influence results in neuroimaging studies using a number of various imaging modalities. No in vivo data exists on whether or not there are ApoE-related changes observable by proton magnetic resonance spectroscopy (MRS). In this study we measured absolute peak areas of proton MR spectra obtained from the occipital cortex in 22 non-demented elderly with (n = 8) or without (n = 14) the ApoE ε4 allele. No statistically significant differences were found in levels of N-acetyl aspartate, myo-inositol, or choline containing compounds between the groups. Instead, compared with the non-carriers, the levels of creatine were significantly lower in the ε4 carriers, suggesting increased metabolic demands in the brain of the ε4 carriers. The levels of creatine also correlated significantly with age and performance on the Mini-Mental State Examination test in the ε4 carriers, but not in the non-carriers. These findings may be of significant clinical interest as potential indicator of incipient AD, and also from therapeutical point of view given the potential neuroprotective effects of creatine. [ABSTRACT FROM AUTHOR]

Objectives – Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia, especially Alzheimer's disease (AD). In follow-up studies, more than 50% of MCI subjects have been converted to dementia in 3–4 years. However, the epidemiology of MCI is not well known. This study was designed to determine the prevalence of MCI in an elderly population. Methods – A total of 806 subjects (60–76 years of age) from a population-based random sample of 1150 subjects living in the city of Kuopio in eastern Finland were evaluated. Neuropsychological tests and a structured interview including the modified Clinical Dementia Rating (CDR) were used to apply the diagnostic criteria of MCI as proposed by Mayo Clinic Alzheimer's Disease Research Centre. Thus, subjects having a test score more than 1.5 SDs below the age appropriate mean in memory tests and a CDR score of 0.5 but no dementia, were diagnosed as having MCI. Results – A total of 43 subjects, 5.3%, met the MCI criteria. MCI was more prevalent in older and less-educated subjects, but no difference was found between men and women. The CDR appeared to be the most important part of the criteria. The memory tests had less impact on prevalence variables. Conclusions – The low prevalence of MCI indicate that in a population-based study design its criteria may identify a more homogeneous group of subjects at the lower end of the cognitive continuum as contrasted with various other criteria of cognitive impairment in the elderly population. This is compatible with follow-up studies showing a high probability of dementia in the MCI group. Thus, probable candidates for trials of preventive intervention for dementia can be screened from the elderly population using these diagnostic criteria. [ABSTRACT FROM AUTHOR]

Background: A beneficial effect of selegiline (l-deprenyl) in Alzheimer's disease (AD) has been reported in several clinical studies. Methods: The brain tissue from 17 deceased patients, members of a double-blind clinical trial to assess the potential benefit of selegiline in AD, were analysed. Findings: In our study, the decrease in the Mini-Mental State Examination (MMSE) scores during the progress of the disease had been significantly influenced by selegiline treatment. Prior to death, the MMSE scores were significantly higher in those patients receiving selegiline than in those receiving placebo. However, according to our results, none of the lesions critical for AD diagnosis, such as counts of senile/neuritic plaques, neurofibrillary tangles or β-A4 load, were influenced by the selegiline treatment. Interpretation: In conclusion, according to our study, mechanisms other than neuronal degeneration seen as lesions critical for AD diagnosis are influenced by selegiline treatment, leading to the functional benefit found in AD. [ABSTRACT FROM AUTHOR]