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We investigated structural and functional changes in the medial temporal lobe (MTL) using magnetic resonance imaging (MRI) and compared the discriminative power of these measures with neuropsychological testing in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Functional MRI (fMRI) was performed in 21 elderly controls, 14 MCI subjects, and 15 mild AD patients during encoding and cued retrieval of word-picture pairs. A region-of-interest-based approach in SPM2 was used to extract the extent of hippocampal activation. The volumes of the hippocampus and entorhinal cortex (EC) were manually outlined from anatomical MR images. Discriminant analyses were conducted to assess the ability of hippocampal fMRI, MTL volumetry, and neuropsychological measures to classify subjects into clinical groups. Entorhinal but not hippocampal volumes differed significantly between the control and MCI subjects. Both entorhinal and hippocampal volumes differed between MCI and AD patients. There were no significant differences in the extent of hippocampal fMRI activation during encoding or retrieval between the groups. Entorhinal volume was the best discriminator with a discriminating accuracy of 85.7% between controls and MCI, 86.2% between MCI and AD, and 97.2% between controls and AD. Delayed recall of a wordlist classified the subjects, second best, with a discriminating accuracy of 81.8% between controls and MCI, 75% between MCI and AD and 93.5% between controls and AD. The accuracy of hippocampal volumetry ranged from 42.9 to 69.4%, and hippocampal fMRI activation during encoding and retrieval had a classification accuracy of only 41.4-57.7% between the groups. Our results suggest that evaluation of entorhinal atrophy, in addition to the prevailing diagnostic criteria, seems promising in the identification of prodromal AD. Future technical improvements may improve the utilization of hippocampal fMRI for early diagnostic purposes.

Structural and functional magnetic resonance imaging (fMRI) was performed on 21 healthy elderly controls, 14 subjects with mild cognitive impairment (MCI) and 15 patients with mild Alzheimer's disease (AD) to investigate changes in fMRI activation in relation to underlying structural atrophy. The fMRI paradigm consisted of associative encoding of novel picture-word pairs. Structural analysis of the brain was performed using voxel-based morphometry (VBM) and hippocampal volumetry. Compared to controls, the MCI subjects exhibited increased fMRI responses in the posterior hippocampal, parahippocampal and fusiform regions, while VBM revealed more atrophy in MCI in the anterior parts of the left hippocampus. Furthermore, the hippocampal volume and parahippocampal activation were negatively correlated in MCI, but not in controls or in AD. We suggest that the increased fMRI activation in MCI in the posterior medial temporal and closely connected fusiform regions is compensatory due to the incipient atrophy in the anterior medial temporal lobe.

Background The patients with mild cognitive impairment (MCI) have an elevated risk for Alzheimer's disease (AD). Especially the amnestic MCI is seen as prodrome of AD. Apolipoprotein E (APOE) ɛ4 allele, abnormal CSF Aβ42, Tau and phosphorylated Tau (phospho-Tau) levels are associated with elevated risk for AD. Methods APOE genotyping was done by PCR based method and baseline CSF Aβ42, Tau and phospho-Tau were measured by ELISA from 60 controls and 79 MCI patients. Results Thirty-three MCI patients developed dementia during an average of 3.5 years follow-up. CSF Aβ42 was decreased and Tau and phospho-Tau were increased in the progressive MCI patients. The APOE ɛ4 allele was more frequent in the progressive MCI patients. The APOE ɛ4 allele showed a dose dependent association to the Aβ42 levels in the progressive MCI patients and to all of the markers in controls. Conclusions Decreased CSF Aβ42 and elevated Tau or phospho-Tau together with APOE ɛ4 allele are highly predictive for the dementia in MCI patients with amnestic or executive symptoms.

Background: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. Objective: To study the pattern of brain atrophy in MCI. Methods: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p

Background Single measurements of plasma Aβ are not useful in the diagnostics of Alzheimer9s disease (AD). However, changes in plasma Aβ levels during repeated testing may be helpful in the prediction and evaluation of progression of the incipient AD or mild cognitive impairment. Objective To examine the relation of baseline and serial plasma Aβ levels to cognitive change in follow-up. Methods 269 subjects (52 cognitively impaired and 217 controls) from a population-based cohort were clinically followed up from 3 to 6 years. Serial plasma samples were available from 70 subjects who were followed up for 3 years and 43 subjects followed for 6 years. The plasma Aβ levels were measured using ELISA. Results Subjects who declined cognitively during the follow-up had lower levels of plasma Aβ42 at the baseline. Plasma Aβ42 and the Aβ42/Aβ40 ratio decreased (−2.4 pg/ml for Aβ42 in 6 years) in those who declined in follow-up, whereas Aβ42 and the Aβ42/Aβ40 ratio increased in the subjects who remained cognitively stable or improved in follow-up. Subjects using acetylsalicylic acid, dipyridamole, antidiabetic or anticoagulant drugs as well as subjects with coronary heart disease had higher levels of Aβ40. Conclusions Low or decreasing plasma Aβ42 during the follow-up is associated with cognitive decline. Serial measurement of plasma Aβ42 may be useful in the detection of the subjects who are at risk for cognitive decline.

Performance in olfactory identification was studied in mild cognitive impairment (MCI), using slightly expanded standard clinical approach to study the olfactory nerve. Four hundred and eighty-six cognitively normal individuals and 72 individuals with MCI underwent spontaneous and cued odor identification and delayed odor recall. Performance in these was compared with the performance in the CERAD version of the Boston Naming Test (BNT). The individuals with MCI scores significantly worse in all tests compared with controls, but the performance in tests assessing odor were less impaired than performance in the BNT. Standard assessment of olfactory nerve function is not sufficient to study cognitive impairment in MCI.

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.

For both clinical and research reasons, it is essential to identify which mild cognitive impairment (MCI) subjects subsequently progress to Alzheimer's disease (AD). The prediction may be facilitated by accelerated whole brain atrophy exhibited by AD subjects. Iterative principal component analysis (IPCA) was used to characterize whole brain atrophy rates using sequential MRI scans for 102 MCI subjects from the Kuopio University Hospital. We modelled the likelihood of progression to probable AD, and found that each additional percent of annualized whole brain atrophy rate was associated with a higher odds ratio (OR) of progression (OR=1.30, p=0.01, 95% CI=1.05-1.60). Our study demonstrates an association between whole brain atrophy rate and subsequent rate of clinical progression from MCI to AD. These findings suggest that IPCA could be an effective brain-imaging marker of progression to AD and useful tool for the evaluation of disease-modifying treatments.

The concept of mild cognitive impairment (MCI) has been proposed to represent a transitional stage between normal aging and dementia. We studied the predictive value of the MRI-derived volumes of medial temporal lobe (MTL) structures, white matter lesions (WML), neuropsychological tests, and Apolipoprotein E (APOE) genotype on conversion of MCI to dementia and AD. The study included 60 subjects with MCI identified from population cohorts. During the mean follow-up period of 34 months, 13 patients had progressed to dementia (9 to Alzheimer's disease (AD)). In Cox regression analysis the baseline volumes of the right hippocampus, the right entorhinal cortex and CDR sum of boxes predicted the progression of MCI to dementia during the follow-up. In a bivariate analysis, only the baseline volumes of entorhinal cortex predicted conversion of MCI to AD. The Mini-Mental State Examination (MMSE) score at baseline, WML load, or APOE genotype were not significant predictors of progression. The MTL volumetry helps in identifying among the MCI subjects a group, which is at high risk for developing AD.

We investigated the effect of apolipoprotein E (ApoE) on the whole brain in 51 individuals with mild cognitive impairment using voxel-based morphometry. Between cases heterozygous for the ApoE Ε4 (n = 15) and those who were ApoE Ε4 noncarriers (n = 28), only the right parahippocampal gyrus, with the entorhinal cortex included, reached the level of statistical significance. In cases homozygous for the Ε4 allele (n = 8) versus noncarriers, the greatest atrophy was located in the right amygdala followed by the right parahippocampal gyrus, the left amygdala and the left medial dorsal thalamic nucleus.

The patients with mild cognitive impairment (MCI) have an elevated risk for Alzheimer's disease (AD). Especially the amnestic MCI is seen as prodrome of AD. Apolipoprotein E (APOE) epsilon4 allele, abnormal CSF Abeta42, Tau and phosphorylated Tau (phospho-Tau) levels are associated with elevated risk for AD.APOE genotyping was done by PCR based method and baseline CSF Abeta42, Tau and phospho-Tau were measured by ELISA from 60 controls and 79 MCI patients.Thirty-three MCI patients developed dementia during an average of 3.5 years follow-up. CSF Abeta42 was decreased and Tau and phospho-Tau were increased in the progressive MCI patients. The APOE epsilon4 allele was more frequent in the progressive MCI patients. The APOE epsilon4 allele showed a dose dependent association o the Abeta42 levels in the progressive MCI patients and to all of the markers in controls.Decreased CSF Abeta42 and elevated Tau or phospho-Tau together with APOE epsilon4 allele are highly predictive for the dementia in MCI patients with amnestic or executive symptoms.