[Show abstract][Hide abstract] ABSTRACT: Objective: To assess effects of EGb 761 ® on cognition and quality of life in subjects with very mild cognitive impairment. Methods: We randomized 300 subjects aged 45 to 65 with cognitive complaints and low functioning (more than one standard deviation below appropriate norm) in at least one cognitive test to double-blind treatment with once daily 240 mg EGb 761 ® or placebo for 12 weeks. Results: The exploratory intention-to-treat analysis showed significant im-provement (p < 0.025, one-sided) beyond practice effects for EGb 761 ® in a measure of attention (Vienna Test System-Work Performance Series) and trends in favour of EGb 761 ® in measures of memory (Wechsler Memory Scale III-Faces I, Appointments Test—delayed recall), and perceived physical health (SF36-factor score Physical Health). Cog-nitive effects were more pronounced and more consistent (p < 0.025 in 4 of 5 tests) in subjects with lower memory func-tion at baseline. Specifically, practice effects in the more demanding tests were attenuated or absent in these subjects. Conclusion: Ginkgo biloba extract EGb 761 ® improved cognitive functioning and aspects of quality of life in subjects with very mild cognitive impairment.
[Show abstract][Hide abstract] ABSTRACT: 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.
Psychiatry Research 07/2010; 183(1):44-51. DOI:10.1016/j.pscychresns.2010.04.003 · 2.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuropsychological assessment is integral part of the diagnostic work-up of dementia. A recent survey
among memory clinics reveals shortcomings regarding test use (ie. screening tests instead of elaborate
batteries) and neuropsychological competence (lack of psychologist positions). For this reason, we want
to depict the scope and the limitations of screening tests and their differentiation from a comprehensive
neuropsychological diagnostic process. Screening instruments are designed to be applied in low-prevalence
settings (e. g. general practice), whereas memory clinics have to constitute the diagnostic reference
via neuropsychological expertise.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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.
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.
International Journal of Geriatric Psychiatry 11/2008; 23(11):1148-55. DOI:10.1002/gps.2042 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: So far goal-oriented therapy in dementia cannot be measured sufficiently. There are no tests that detect a profile of capacities that could describe the targets of training. Thus, it was aimed to develop a test that uncovers a profile of capacities in patients suffering from dementia.
Three groups of subjects (n = 156), 30 patients suffering from dementia of the Alzheimer type, 28 from depressive disorder and 98 healthy age-comparable controls were included in the study. Building on already existing tests, items were developed to cover intelligence, visuo-spatial abilities, cognitive and social problem solving, emotional and executive abilities. All subjects were investigated with the Training Target Test Dementia (3TD). To calculate convergence validity, the Test for the Early Detection of Dementia from depression (TE4D) and the Beck Depression Inventory were assessed. Descriptively, profiles were calculated. Group differences were studied with the Kruskal-Wallis and the Mann-Whitney-U-test.
Characteristic neuropsychological capacity profiles were found within the three groups. Differences between the groups were significant for all subtests. Significantly, the 3TD separated patients with dementia from controls. It reached high sensitivity and acceptable specificity. The convergence validity to the TE4D was significant (r = 0.77).
The capacity profiles detected may allow for specified therapeutic modules to be scheduled. Moreover, the 3TD will be suitable to discriminate between patients suffering from dementia, depression as well as healthy age-comparable controls. For therapeutic improvement, further investigation will be needed to prove its sensitivity.
International Journal of Geriatric Psychiatry 07/2008; 23(12):1239-44. DOI:10.1002/gps.2057 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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%.
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.
Aging clinical and experimental research 06/2007; 19(3):255-8. DOI:10.1007/BF03324698 · 1.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
International Journal of Geriatric Psychiatry 08/2004; 19(8):749-53. DOI:10.1002/gps.1162 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychometric tests used for the early detection of dementia often are seen as too difficult or too complex. Classical neuropsychologic tests were not developed for this purpose. Sensitivity and specificity to discriminate "healthy" vs. "ill" are low. For measuring both dementive and depressive symptoms, so far no test has been published. The objective of this study was to develop a sensitive and specific test for dementia that is easy to administer and to evaluate. Moreover, it should discriminate dementia from depressive pseudodementia. With respect to former studies, items were selected that recognized patients in the beginning of the disease. Additionally, depressive symptoms were rated. With the items for dementia, 88 patients with dementia of the Alzheimer type, 52 patients with depressive disorder and 37 healthy elderly controls were investigated. In this group of already diagnosed patients, the test reached a sensitivity and specificity of 100 percent (healthy elderly controls vs. patients with Alzheimer's disease: n = 125, U = 0, p < 0.001; patients with depressive disorder vs. patients with Alzheimer's disease: n = 140, U = 0, p < 0.001; healthy elderly controls vs. patients with depressive disorder: n = 89, U = 485.5, p < 0.001). For the dementia items, the inter-rater-reliability was rs = 0.996 (p < 0.001, n = 18), for the depression items it was rs = 0.753 (n = 18, p < 0.001). The test-retest-reliability was rs = 0.868 (p < 0.001, n = 35) for the dementia items and rs = 0.7 (n = 8, p < 0.05) for the depression items. These validation data will make the test useful for practitioners. Its ability to discriminate patients suffering from dementia of the Alzheimer type from healthy controls is comparable to tests consuming more time.
[Show abstract][Hide abstract] ABSTRACT: In clinical and drug studies, different neuropsychometric tests are used. So far, no empirical data have been published to compare studies using different tests. The purpose of this study was to calculate a regression formula allowing a comparison of cross-sectional and longitudinal data from three neuropsychometric tests that are frequently used in drug studies (Alzheimer's Disease Assessment Scale, ADAS-cog; Syndrom Kurz Test, SKT; Mini Mental State Examination, MMSE).
177 patients with dementia according to ICD10 criteria were studied for the cross sectional and 61 for the longitudinal analysis. Correlations and linear regressions were calculated between tests. Significance was proven with ANOVA and t-tests using the SPSS statistical package.
Significant Spearman correlations and slopes in the regression occurred in the cross sectional analysis (ADAS-cog-SKT r(s) = 0.77, slope = 0.45, SKT-ADAS-cog slope = 1.3, r2 = 0.59; ADAS-cog-MMSE r2 = 0.76, slope = -0.42, MMSE-ADAS-cog slope = -1.5, r2 = 0.64; MMSE-SKT r(s) = -0.79, slope = -0.87, SKT-MMSE slope = -0.71, r2 = 0.62; p<0.001 after Bonferroni correction; N = 177) and in the longitudinal analysis (SKT-ADAS-cog, r(s) = 0.48, slope = 0.69, ADAS-cog-SKT slope = 0.69, p<0.001, r2 = 0.32, MMSE-SKT, r(s) = 0.44, slope = -0.41, SKT-MMSE, slope = -0.55, p<0.001, r2 = 0.21).
The results allow calculation of ADAS-scores when SKT scores are given, and vice versa. In longitudinal studies or in the course of the disease, scores assessed with the ADAS-cog and the SKT may now be statistically compared. In all comparisons, bottom and ceiling effects of the tests have to be taken into account.
[Show abstract][Hide abstract] ABSTRACT: Objective: Numerous tests have been developed to detect dementia. Concerning data on validity, head to head comparisons are rare. To evaluate, which test show higher sensitivity and specificity for the screening of dementia, the Mini-Mental-Status-Examination (MMSE) and the Test for The Early Detection of Dementia with Discrimination from Depression (TE4D) were compared in a German-speaking population. Methods: MMSE and the TE4D were assessed in 139 patients with Alzheimer's Disease (AD), 93 with depressive disorder (DEP) and in 21 healthy controls. Diagnosis was made without knowledge of the test results. The ADAS-Cog and the SKT were additionally