The relation of regional cerebral perfusion and atrophy in mild cognitive impairment (MCI) and early Alzheimer's dementia.

The spatial and temporal relations between regional cerebral blood flow (rCBF) and brain volume (rVOL) changes in incipient and early Alzheimer's dementia (AD) are not fully understood. The participants comprised 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD who were examined using structural and perfusion-weighted magnetic resonance imaging (MRI) at 1.5 Tesla. Hippocampus and amygdala volumes were measured by manual volumetry. A region-of-interest co-localisation method was used to calculate rCBF values. DNA samples were genotyped for apolipoprotein E (APO E). In comparisons of AD with MCI, rCBF was reduced in the posterior cingulum only, while profound rVOL reductions occurred in both right and left amygdala and in the right hippocampus, and as a trend, in the left hippocampus. Brain volumes of the hippocampus and the amygdala were uncorrelated with the respective rCBF variables in both MCI and AD. Hippocampal but not amygdalar volumes were associated with presence of one or two APOE epsilon4 alleles in MCI and mild AD, while there was no association of APOE epsilon4 allele with rCBF. These data support earlier indications that rCBF and rVOL changes are at least partly dissociated in the early pathogenesis of AD and heterogeneously associated with the APOE risk allele. The data also support the concept of functional compensatory brain activation and the diaschisis hypothesis as relevant in incipient and early AD.

Blood biomarkers of osteoporosis in mild cognitive impairment and Alzheimer's disease.

Previous studies revealed some comorbidity of Alzheimer's disease and osteoporosis not only for advanced disease, but also for the incipient conditions cognitive decline and decline of bone mineral density. To detect comorbidity with osteoporosis at a subclinical level, we studied concentrations of biochemical osteoporosis markers in blood plasma of subjects with mild cognitive impairment and mild Alzheimer's disease compared to subjects with primary osteoporosis and age-matched cognitively normal controls in an explorative approach. Regarding disease-spanning molecular pathology we also studied osteoprotegerin, a decoy receptor of RANKL and TRAIL. Equally increased C-terminal collagen fragments, marking bone catabolism, were seen in osteoporosis and Alzheimer's disease (+68%) versus controls. Osteocalcin, marking bone remodelling and anabolism, was concomitantly increased in osteoporosis (+63%), as a trend, and significantly in Alzheimer's disease (+76%). Osteoprotegerin was unchanged between patient groups and controls. 25 (OH) vitamin D plasma levels were low normal and of equal amount in all groups except for the osteoporosis group. These results point to increased bone catabolism and concomitant remodelling/anabolism unrelated to vitamin D state in mild Alzheimer's disease, but not in mild cognitive impairment. This corroborates previous findings of comorbidity of Alzheimer's disease with osteoporosis in the early disease course at the level of biochemical blood markers. Regarding osteoprotegerin, previously reported plasma level increases in Alzheimer's disease were not observed in this study, which does not rule out subtle changes to be detected in larger samples or the possibility that other components of osteoprotegerin pathways are affected in Alzheimer's disease.

Quantitative EEG in progressing vs stable mild cognitive impairment (MCI): results of a 1-year follow-up study.

OBJECTIVE: The study objective is to evaluate the use of qEEG data for the cross-sectional differentiation of mild cognitive impairment (MCI) from mild Alzheimer's disease (AD) and in the longitudinal prediction of cognitive decline in MCI. METHODS: Eighty-eight subjects with MCI and 42 subjects with mild probable AD were enrolled. Baseline EEGs were recorded using a 32-channel system with electrode positioning according to the international 10-20 system. Digitalized EEG data were further studied by quantitative spectral analysis. Study subjects were followed up for 1 year and reassessed psychometrically. An increase of the total ADAS-cog score of >or= 4 points was regarded as a significant cognitive decline. Using this cut-off, MCI subjects were sub-grouped into stable MCI (s-MCI) and progressing MCI (p-MCI). RESULTS: AD subjects and p-MCI subjects were differentiated from s-MCI subjects by a reduction of alpha power over posterior leads. Reduction of alpha power and mean frequency were significantly correlated with poorer cognitive performance in psychometric tests. Baseline values of alpha power over posterior leads had the highest positive predictive power for MCI and AD (69-80%) and predicted cognitive decline in MCI within a 1-year follow up. CONCLUSIONS: qEEG revealed decreased alpha activity in progressing MCI and mild AD prior to an increase of slow wave activity, which typically occurs in advancing AD. This finding may reflect an affection of thalamo-cortical relay activity and cortical connectivity in the early disease course of AD. Reduced alpha activity in MCI subjects at baseline may have prognostic value regarding future cognitive decline.

Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging.

The utility of perfusion-weighted magnetic resonance imaging (PW-MRI) for detecting changes in regional cerebral blood flow (rCBF) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) was evaluated. Thirteen cognitively normal (CN) elderly subjects, 35 mostly amnestic MCI subjects and 20 subjects with mild probable AD were enrolled. During i.v. injection of gadopentetate dimeglumine, a dynamic T2*-weighted single-shot EPI sequence was conducted using a 1.5-T scanner. Frontobasal (FROB), temporoparietal (TPAR), mesiotemporal (MTMP), anterior and posterior cingular (ACING, PCING), amygdala (AMYG), thalamus and cerebellar brain regions were studied. rCBF was computed from regional cerebral blood volume and arterial input function and normalised to white matter. Images were analysed by manually placed regions of interest using anatomical coregistration. Significant decreases of rCBF were detected in MCI vs. CN in MTMP (-23%), AMYG (-20%) and ACING (-15%) with no further decline in mild AD. In PCING hypoperfusion (-10%) was confined to AD. These hypoperfusional changes are a possible correlate of localised impairment of CNS function. In FROB no perfusion changes were observed between diagnostic groups, but hyperperfusion was observed in mild dementia stages, possibly reflecting functional compensatory mechanisms. These data suggest that PW-MRI detects specific changes in rCBF not only in AD, but also in amnestic MCI, a disorder suggested to largely represent a pre-dementia stage of AD. This method may thus be useful in both research and clinical applications to detect early functional brain changes in the pathogenesis of dementias.

Odor identification in Alzheimer's disease and depression.

BACKGROUND AND AIMS: In Alzheimer's disease (AD) olfactory deficits are common and depression is a difficult differential diagnosis. We therefore investigated the usefulness of an odor identification test to differentiate both conditions. METHODS: Twenty patients with probable Alzheimer's disease (AD), twenty elderly patients with a depressive disorder, and thirty healthy elderly subjects performed a German odor identification test. RESULTS: AD patients had significantly lower odor identification scores, compared with both depressive patients and control subjects (F=121.96, df=2, 67, p<0.001). With a cut-off score of 10/11, the sensitivity of the identification test to differentiate AD patients from depressive patients was 100%, and specificity was 95%. CONCLUSIONS: The odor identification test used in this study is able to reveal olfactory deficits in AD. It also seems to be a useful instrument to differentiate AD from depression.

EEG and the Test for the Early Detection of Dementia with Discrimination from Depression (TE4D): a validation study.

OBJECTIVE: The Test for the Early Detection of Dementia with Discrimination from Depression (TE4D) was developed as a screening instrument for mild dementia. We investigated the convergent validity of the TE4D to EEG and other psychometric tests in patients suffering from dementia and depression. METHOD: In 47 patients suffering from Alzheimer's disease (ICD-10 F.00) and 16 patients with affective disorders (F30-F39) the tests TE4D, ADAS-cog, SKT, BCRS, MMSE were performed and an EEG recorded. Group differences were compared by t-tests and a regression analysis was calculated. RESULTS: The inter-test-correlations varied between rs = 0.77 and rs = 0.91. Significant differences between the diagnostic groups were found for all tests as well as for the frequency bands alpha and beta. For the qEEG, significant positive correlations were found between TE4D (Dementia subscore) and the mean frequency (r = 0.47), the peak frequency (r = 0.42), the frequency bands alpha (r = 0.59) and beta (r = 0.56) as well as negative correlations in the frequency bands delta (r = -0.23) and theta (r = -0.42). The mean frequency and the activity in the frequency bands alpha, beta2, delta and theta contributed to the regression equation. The correlation between regression equation and the TE4D was rs = 0.87. The other tests also correlated with the TE4D: ADAS rs = -0.75, MMST rs = 0.82, SKT rs = -0.74, BCRS rs = -0.83. CONCLUSION: The TE4D showed convergent validity with the EEG parameters. Both the TE4D-score and the EEG-alterations correlated significantly with the degree of severity of Alzheimer's disease. This result underlines the assumption that the TE4D will be a useful instrument for the diagnostic process in dementia.