Hans Förstl


K2 - SFB 258 DFG:

Multi-dimensional Longitudinal Study on

Ageing, Alzheimer Dementia and Frontotemporal Degeneration:

Cognition, BPSD, EEG, Volumetric Brain Changes and Molecular Biology




Rofo. 1998 Jan;168(1):97-100. Links
[Neuroradiological findings in Alzheimer dementia with the presenile mutation]
[Article in German]
•    Hentschel F,
•    Zerfass R,
•    Becker G,
•    Beyreuther K,
•    Forstl H.
Abt. Neuroradiologie, Klinikums Mannheim.
PMID: 9501942 [PubMed - indexed for MEDLINE]



J Neural Transm Suppl. 1998;54:201-10. Links
Changes of intracellular calcium regulation in Alzheimer's disease and vascular dementia.
•    Eckert A,
•    Forstl H,
•    Zerfass R,
•    Oster M,
•    Hennerici M,
•    Muller WE.
Department of Psychopharmacology, Klinikum Mannheim, University of Heidelberg, Federal Republic of Germany.
Free intracellular calcium ([Ca2+]i) represents probably the most important intracellular messenger for many signal transduction pathways. Due to this crucial role of [Ca2+]i, it has been assumed that alterations of [Ca2+]i are critically involved in brain aging and in the pathophysiology of Alzheimer's disease (AD). This hypothesis is corroborated by several studies demonstrating changes of [Ca2+]i in peripheral cells from AD patients. However, the findings are still controversial. Using blood lymphocytes and neutrophils as two different peripheral model systems, we evaluated several parameters of intracellular Ca2+ regulation in a very large group of AD patients and non-demented controls. We found no major difference in Ca2+ homeostasis, since neither the basal [Ca2+]i, nor the activation-induced Ca2+ responses differed among neutrophils or lymphocytes from aged controls and AD patients. However, we observed a delayed Ca2+ response of AD lymphocytes after phytohemagglutinin (PHA) stimulation indicating an impaired function of Ca2+ influx-controlling mechanisms. Furthermore, we studied whether differences exist in Ca2+ regulation between lymphocytes from patients with vascular dementia and AD patients, to define AD-specific alterations and to distinguish between the two dementia groups and non-demented control subjects respectively. First evidences indicate that Ca2+ mobilization in lymphocytes is specifically impaired in lymphocytes from patients with vascular dementia.
PMID: 9850929 [PubMed - indexed for MEDLINE]



Electroencephalogr Clin Neurophysiol. 1997 Aug;103(2):241-8. Links
Discrimination of Alzheimer's disease and normal aging by EEG data.
Besthorn C,
•    Zerfass R,
•    Geiger-Kabisch C,
•    Sattel H,
•    Daniel S,
•    Schreiter-Gasser U,
•    Forstl H.
Zentralinstitut fur Seelische Gesundheit, Mannheim, Germany.
Quantitative EEG results in Alzheimer's disease may be summarized by the term 'slowing', i.e. slow frequencies (delta, theta) are increased and fast frequencies (alpha, beta) are decreased. But how can EEG data be used to discriminate AD patients from controls by means of EEG data? Discriminant analysis may produce false predictions using too many predictors, as is often the case in EEG studies. We studied 4 approaches to this problem: Classification by group means, stepwise discriminant analysis, a neuronal network using back propagation and discriminant analysis preceded by principal components analysis (PCA). A maximum of 86.6% correct classifications was reached using the last mentioned approach with EEG data alone. Including age as a moderator variable in a subgroup, 95.9% correct classifications were reached.
PMID: 9277627 [PubMed - indexed for MEDLINE]



Neurobiol Aging. 1997 May-Jun;18(3):281-4.   Links
Free intracellular calcium in peripheral cells in Alzheimer's disease.
•    Eckert A,
•    Forstl H,
•    Zerfass R,
•    Hennerici M,
•    Muller WE.
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
The goal of the present study was to evaluate several parameters of free intracellular Ca2+ regulation ([Ca2+]i) in Alzheimer's disease (AD) in a very large group of patients (n = 50) and nondemented controls (n = 41), using blood lymphocytes and neutrophils as two different peripheral model systems. We found no major difference, because neither the basal [Ca2+]i, nor the activation-induced Ca2+ responses differed among neutrophils or lymphocytes from aged controls and AD patients. However, we observed a delayed Ca2+ response of AD lymphocytes after phytohemagglutinin (PHA) stimulation, indicating an impaired function of Ca2+ influx-controlling mechanisms, because Ca2+ release from intracellular stores appears to be unchanged. Because the PHA-induced Ca2+ response in lymphocytes is accelerated by beta-amyloid (Beta A) similarly to its effects on central neurons, we also investigated the effect of beta A on Ca2+ signalling with regard to AD-related alterations. In contrast to lymphocytes from aged controls, the amplifying effect on Ca2+ signalling was significantly reduced in lymphocytes from a high percentage of AD patients. The results are discussed with respect to their diagnostic potential and to a possible involvement of altered beta A sensitivity of lymphocytes in the pathophysiology of AD.
PMID: 9263192 [PubMed - indexed for MEDLINE]


Psychiatr Prax. 1997 Mar;24(2):84-7. Links
[Degree of disability of demented patients as judged by relatives and experts (disability insurance)]
[Article in German]
•    Zerfass R,
•    Daniel S,
•    Sattel H,
•    Besthorn C,
•    Forstl H.
Zentralinstitut fur Seelische Gesundheit, Mannheim.
Health insurance companies commission medical expert opinions rating the severity of clinical improvement in order to provide adequate nursing support. We compared these ratings on 28 demented patients with the ratings from carers and with our own examination. The results indicate that the expert opinions underestimated the severity of improvement and adequate support in some of the cases. We discuss whether these discrepancies may be due to the peculiarities of dementia.
PMID: 9190617 [PubMed - indexed for MEDLINE]



Fortschr Neurol Psychiatr. 1996 Jun;64(6):228-33. Links
[Self and informant perception of clinical manifestations of Alzheimer dementia: results of a structured interview (CAMDEX)]
[Article in German]
•    Forstl H,
•    Geiger-Kabisch C,
•    Sattel H,
•    Besthorn C,
•    Schreiter-Gasser U,
•    Abrahams CM,
•    Biedert S.
Psychiatrische Klinik, Zentralinstitut fur Seelische Gesundheit, Mannheim.
The correlations between (a) the patients' memory complaints, (b) the informants' rating of the patients' cognitive impairment, and (c) cognitive performance according to the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) were examined in 163 patients with probable or possible Alzheimer's disease. The patients' complaints were weakly correlated with informants' view (p < 0.05), closely correlated with depressive mood (p < 0.0001), but not with cognitive performance or the stage of dementia. The results of Clinical Dementia Rating, Mini-Mental State Examination and the Cambridge Cognitive Examination were significantly correlated with the informants' rating of cognitive impairment (p < 0.0001). These results are in line with previous studies and confirm (1) the suitability of CAMDEX for the structured examination of dementia patients and their caregivers, (2) the association between affective disturbances and the perception of cognitive deficits, and (3) the importance informants' rating for the valid evaluation of demented patients.
PMID: 8766996 [PubMed - indexed for MEDLINE]



J Biol Chem. 1996 Sep 13;271(37):22908-14.   Links
Analysis of heterogeneous A4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive Western blot assay.
•    Ida N,
•    Hartmann T,
•    Pantel J,
•    Schroder J,
•    Zerfass R,
•    Forstl H,
•    Sandbrink R,
•    Masters CL,
•    Beyreuther K.
Center for Molecular Biology Heidelberg (ZMBH), University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
The betaA4 peptide, a major component of senile plaques in Alzheimer's disease (AD) brain, has been found in cerebrospinal fluid (CSF) and blood of both AD patients and normal subjects. Although betaA4 1-40 is the major form produced by cell metabolism and found in CSF, recent observations suggest that the long-tailed betaA4 1-42 plays a more crucial role in AD pathogenesis. Here, we established new monoclonal antibodies against the C-terminal end of betaA4 1-40 and 1-42, and used them for the specific Western blot detection. After optimizing the assay conditions, these antibodies detected low picogram amount of betaA4, and both betaA4 1-40 and 1-42 levels in CSF could be determined by direct loading of the samples. Blood levels of betaA4 1-40 and 1-42 were also determined by specific immunoprecipitation followed by Western blot detection. We found that CSF betaA4 1-42 level is lower in AD patients compared with non-demented controls, although there was a significant overlap between the groups. The level of betaA4 1-40 in CSF, and of betaA4 1-40 as well as betaA4 1-42 in plasma, were not different between AD patients and controls. Besides the 4-kDa full-length betaA4 band, we could also detect several N-terminal variants of betaA4 in CSF and plasma of both AD patients and controls. Two N-terminally truncated betaA4 species migrating at the position of 3.3 and 3.7 kDa were found in CSF, while 3.7- and 5-kDa forms were found in plasma. The relative abundance of these various species were considerably different in the CSF and plasma, suggesting that the cellular source and/or clearance of betaA4 is different in these two compartments.
PMID: 8798471 [PubMed - indexed for MEDLINE]



Life Sci. 1996;59(5-6):499-510. Links
Lymphocytes and neutrophils as peripheral models to study the effect of beta-amyloid on cellular calcium signalling in Alzheimer's disease.
•    Eckert A,
•    Forstl H,
•    Zerfass R,
•    Hartmann H,
•    Muller WE.
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
According to the calcium hypothesis of brain aging, disturbances of free intracellular calcium homeostasis ([Ca2+]i) play a key role in pathology of Alzheimer's disease (AD). Recent data from neuronal tissue culture support the contribution of the beta-amyloid peptide (beta A) to neurodegeneration in AD, probably by disruption of the intracellular Ca2+ regulation. On the basis of this premise, we used peripheral blood cells to examine the role of beta A on Ca2+ signalling, not only to obtain an experimental approach to investigate these effects of beta A in man, but also to search for AD-specific alterations of the effects of beta A on Ca2+ signalling. This approach is based on observations indicating that the phytohemagglutinin (PHA)-induced Ca2+ response in circulating human lymphocytes of healthy volunteers is affected by beta A and its fragment 25-35 in a fashion similar to its effects on central neurons, whereas we found no effect of beta A on receptor-activated Ca2+ response in neutrophils. Therefore, we used human blood lymphocytes as peripheral model systems to search directly for AD-related abnormalities of Ca2+ regulation, for alterations of beta A effects on Ca2+ signalling and on membrane fluidity, and for possible changes of potassium channels. In accordance with our data in neutrophils, we were unable to identify any relevant change of the PHA-induced Ca2+ elevations in lymphocytes, which is not supporting the assumption of general alterations of cellular Ca2+ regulation in AD. On the other hand, the amplifying effect of beta A on Ca2+ signalling was significantly reduced in lymphocytes from AD patients. Moreover, Ca2+ responses to beta A25-35 were not different between early- and late-onset AD patients. Our findings indicate that the sensitivity of the lymphocyte for the effects of beta A is reduced in a high percentage of patients with probable or possible AD. As possible explanation we observed a similar reduction of the sensitivity of the lymphocyte membrane for the fluidity-decreasing properties of beta A. Finally, the inhibition of the PHA-induced Ca2+ response by tetraethylammonium (TEA) was lower in the AD group compared to aged controls. This could suggest the presence of a K+ channel dysfunction on AD lymphocytes, as it has been shown on skin fibroblasts of AD patients.
PMID: 8761338 [PubMed - indexed for MEDLINE]



Br J Psychiatry. 1996 Mar;168(3):280-6. Links
Longitudinal cognitive, electroencephalographic and morphological brain changes in ageing and Alzheimer's disease.
•    Forstl H,
•    Sattel H,
•    Besthorn C,
•    Daniel S,
•    Geiger-Kabisch C,
•    Hentschel F,
•    Sarochan M,
•    Zerfass R.
BACKGROUND. The natural course of cognitive performance, electrophysiological alterations and brain atrophy in ageing and Alzheimer's disease (AD) has been investigated in numerous studies, but only few attempts have been made to examine the relationship between clinical, electroencephalographic (EEG) and morphological changes with quantitative methods prospectively over longer periods of time. METHOD. Fifty-five patients with clinically diagnosed AD and 66 healthy elderly controls were examined biannually using a cognitive test (CAMCOG), EEG band power and volumetric estimates of brain atrophy. RESULTS. On average cognitive performance deteriorated by 28 points on the CAMCOG in the AD group, the alpha/theta ratio decreased by 0.2, and the proportion of intracranial cerebrospinal fluid volume increased by 3.5% during a 2-year period. Similar changes were observed after a second 2-year interval. A multiple regression model demonstrated a significant influence of age on cognition and atrophy and a significant influence of the estimated duration of symptoms on cognition, alpha/theta ratio and brain atrophy at the initial examination. Cognitive performance at the first examination exerted significant effects on the performance and also on brain atrophy at re-examination after 2 or 4 years, whereas the EEG and neuroimaging findings at the previous examination were exclusively related to the corresponding findings at the follow-up examinations. In the control group no significant cognitive, EEG and morphological changes were observed after 2 and 4 years. CONCLUSION. After 2 consecutive follow-up periods, we were able to verify significant deteriorations of cognition accompanied by neurophysiological and neuroradiological changes in AD, but not in normal ageing. In clinically diagnosed AD, cognitive performance at the followup examination could not be predicted by the previous alpha/theta ratio or by the previous degree of global brain atrophy, whereas the cognitive test score determined not only performance, but also structural findings at follow-up. Performance on cognitive tests appears to be a more sensitive indicator of the degenerative process than EEG band-power and morphological changes in manifest AD. Neuroimaging, neurophysiology and genetic risk markers may be more important for the early differential diagnosis than for the prediction of the course of illness.
PMID: 8833680 [PubMed - indexed for MEDLINE]


J Neural Transm Suppl. 1996;47:169-81. Links
Quantitative EEG in frontal lobe dementia.
•    Besthorn C,
•    Sattel H,
•    Hentschel F,
•    Daniel S,
•    Zerfass R,
•    Forstl H.
Central Institute of Mental Health, Mannheim, Federal Republic of Germany.
A study on quantitative EEG in 14 patients with frontal lobe dementia (FLD), 14 patients with Alzheimer's disease (AD), and 14 healthy controls was conducted using a complete set of EEG parameters: band power, coherence and fractal dimension. Contrary to earlier studies, we observed higher theta power and sagittal interactions in higher frequency bands in the FLD than in the control group. Lateral interactions of coherence and two indices of fractal dimension were lower in FLD than in controls. There was greater electrophysiological resemblance between the control group and FLD than between any of these groups and AD. This was documented by the results of a discriminant analysis which led to a correct overall classification of 66% of the subjects with misclassifications occurring primarily between control and FLD group.
PMID: 8841964 [PubMed - indexed for MEDLINE]


Dementia. 1996 Jan-Feb;7(1):27-34. Links
Frontal lobe degeneration and Alzheimer's disease: a controlled study on clinical findings, volumetric brain changes and quantitative electroencephalography data.
•    Forstl H,
•    Besthorn C,
•    Hentschel F,
•    Geiger-Kabisch C,
•    Sattel H,
•    Schreiter-Gasser U.
Central Institute of Mental Health, Mannheim, Germany.
Ten patients with a clinical diagnosis of frontal lobe degeneration (FLD) were compared with a group of patients with probable Alzheimer's disease (AD) and with nondemented controls matched for gender and age. In comparison with AD, the duration of illness was slightly shorter and cognitive performance was better in patients with FLD. The greatest enlargement of cerebrospinal fluid volumes was found in FLD and this effect was most pronounced in the anterior fissure and lateral ventricles. Estimates of EEG band-power and EEG coherence in FLD were not remarkably different from nondemented controls, whereas delta- and theta-power were significantly increased in AD. These observations may indicate different disease processes with a dissociation of volumetric computed tomography and quantitative EEG changes, which may be of differential diagnostic value.
PMID: 8788079 [PubMed - indexed for MEDLINE]



Nervenarzt. 1996 Jan;67(1):53-61. Links
[Volumetric brain changes and quantitative EEG in normal aging and Alzheimer's dementia]
[Article in German]
•    Forstl H,
•    Besthorn C,
•    Sattel H,
•    Zerfass R,
•    Geiger-Kabisch C,
•    Schreiter-Gasser U,
•    Hentschel F.
Zentralinstitut fur Seelische Gesundheit, Mannheim.
We studied (1) the differences of volumetric estimates of brain atrophy in normal ageing and Alzheimer's disease (AD); (2) the correlation of these estimates with age and cognitive performance; (3) the differences between absolute EEG power between ageing and AD; (4) the correlation between EEG power and age or cognitive performance; and (5) the correlation between volumetric and EEG data. 84 patients with a clinical diagnosis of AD and 45 age-approximated non-demented controls between 48 and 91 years of age were examined. For statistical comparisons the volumetric estimates of intracranial cerebrospinal fluid (csf) spaces were converted into percentages of total intracranial volume. The EEG was recorded from 17 locations at resting conditions, eyes closed, according to the 10/20 system. Logtransformed absolute band powers were compared between the AD and control groups and correlated with clinical and volumetric findings. The total intracranial csf-space, both lateral ventricles, the third ventricle, anterior, lateral and posterior fissures were significantly larger in AD than in non-demented controls. In normal ageing the csf-volumes were significantly correlated with age, whereas age and cognitive performance were differentially correlated with these variables in AD. In AD, the absolute delta or theta power was significantly higher in all locations, whereas alpha power was lower than in normal controls. These differences were significantly correlated with cognitive performance. There were no significant correlations between the csf-volumes and EEG-power in AD and the control group with one exception: we found a significant inverse correlation between the volumes of the anterior and posterior fissure and the alpha-1 and alpha-2 power independent of electrode location in AD. We conclude that the morphological and EEG-changes in AD are largely independent and suggest that the functional relationship between alpha-power and anterior or posterior fissure volume needs further examination.
PMID: 8676989 [PubMed - indexed for MEDLINE]



Br J Psychiatry. 1995 Dec;167(6):739-46. Links
Brain atrophy in normal ageing and Alzheimer's disease. Volumetric discrimination and clinical correlations.
•    Forstl H,
•    Zerfass R,
•    Geiger-Kabisch C,
•    Sattel H,
•    Besthorn C,
•    Hentschel F.
Central Institute of Mental Health, Mannheim, Germany.
BACKGROUND: We examined the differences in volume of the ventricular and extracerebral cerebrospinal fluid spaces in normal ageing and in probable Alzheimer's disease (AD) and we tried to investigate the effects of the severity of illness on the morphometric differentiation of AD and ageing, the principal components underlying brain atrophy in both conditions, and the correlations of these measurements with clinical findings. METHOD: Forty patients with probable AD were matched with 40 non-demented elderly controls. Both groups underwent standardised clinical tests and unenhanced cranial computed tomography for post hoc volumetric analysis. RESULTS: The lateral and third ventricles and the anterior and lateral fissures were significantly larger in AD than in normal ageing. The volumes of the lateral ventricle and lateral fissure permitted a highly efficient differentiation between normal ageing and AD even at the mild stage of dementia, and this differentiation was improved further in the more severe stages of illness. We identified one principal component underlying brain atrophy in normal ageing and two components in AD: a 'grey matter' component accounting for sulcal and third ventricular enlargement, and a 'white matter' component for lateral ventricular enlargement. In AD, most of the volumetric measurements were significantly correlated with cognitive impairment, but in the group of non-demented elderly controls they were correlated with age. CONCLUSION. Volumetric indices of brain atrophy permit a highly efficient differentiation between normal ageing and AD even in the mild stages of illness and this demonstrates that substantial structural brain changes have developed in the preclinical phase of illness. We suggest that there is an uncoupling between lateral ventricular enlargement and cortical brain atrophy in AD.
PMID: 8829740 [PubMed - indexed for MEDLINE]


Rofo. 1995 Jul;163(1):88-90. Links
[Corticobasal degeneration in computed tomography and magnetic resonance tomography--represented by 2 patients]
[Article in German]
•    Hentschel F,
•    Braus DF,
•    Zerfass R,
•    Forstl H.
Zentralinstitut fur Seelische Gesundheit, Mannheim.
PMID: 7626762 [PubMed - indexed for MEDLINE


Electroencephalogr Clin Neurophysiol. 1995 Aug;95(2):84-9. Links
Parameters of EEG dimensional complexity in Alzheimer's disease.
•    Besthorn C,
•    Sattel H,
•    Geiger-Kabisch C,
•    Zerfass R,
•    Forstl H.
Zentralinstitut fur Seelische Gesundheit, Mannheim, Germany.
The dimensional complexity or fractal dimension of the EEG recorded at 17 locations from the 10-20 system was studied using a very fast new algorithm. The paper contains 2 parts. First, the influence of several parameters (embedding dimension, delay time, high and low frequency cutoff, ADC precision and sweep length) on the estimation of dimensional complexity is investigated. Then it is shown that patients with Alzheimer's disease (n = 50) have significantly lower dimensional complexity than age-approximated non-demented controls (n = 42).
PMID: 7649009 [PubMed - indexed for MEDLINE]



Psychiatr Prax. 1995 Mar;22(2):68-71. Links
["Alzheimer family group": a systematic study of the needs and experiences of caregivers]
[Article in German]
•    Forstl H,
•    Geiger-Kabisch C.
Zentralinstitut fur Seelische Gesundheit, Mannheim.
We evaluated the expectations and experience of 34 participants from a caregivers' support group. In comparison with the husbands, the wives of demented patients attended more regularly and for a longer period of time. Wives expected and experienced emotional support, whereas husbands were more interested in obtaining information about the medical causes of dementia and about patient management. Wives and daughters admitted to greater emotional and physical distress. The role and efficiency of caregivers' support groups should be studied prospectively, particularly because dementia-related problems posed on individual families on one hand and on the public health sector on the other are expected to increase during the next decades.
PMID: 7761542 [PubMed - indexed for MEDLINE]



Arzneimittelforschung. 1995 Mar;45(3A):394-7. Links
Age-associated memory impairment and early Alzheimer's disease. Only time will tell the difference.
•    Forstl H,
•    Hentschel F,
•    Sattel H,
•    Geiger-Kabisch C,
•    Besthorn C,
•    Czech C,
•    Monning U,
•    Beyreuther K.
Zentralinstitut fur Seelische Gesundheit, Mannheim, Fed. Rep. of Germany.
A reliable and early diagnosis of incipient Alzheimer's disease (AD) is one of the obligatory requirements for timely and potentially successful therapeutic intervention. The potential diagnostic significance of mild cognitive impairment and subjective memory complaints was examined. Groups of patients with age-associated memory impairment (AAMI) and with AD were examined prospectively and their subjective complaints, cognitive performance and neuroimaging findings were compared with those of healthy elderly controls. Subjective complaints were most severe in the AD group. Both, memory complaints and depressive disturbances had high loadings on one underlying principal component. There was no statistical correlation between a global score of cognitive performance and subjective complaints in the patient groups, but the correlation between performance and brain atrophy was statistically significant. The degree of brain atrophy, but not subjective complaints (or the diagnostic distinction between AAMI and AD) were associated with the severity of cognitive deterioration during a 2-year follow-up period. This, and the observation of an increased frequency of the apolipoprotein E allele 4 in the AD and AAMI groups, suggest that biological risk markers will be of greater significance for the early diagnosis of AD than the patient's subjective complaints. Patients satisfying criteria for AAMI need to be followed-up, because no reliable diagnostic markers for the earliest or preclinical stages of AD are available to date.
PMID: 7763332 [PubMed - indexed for MEDLINE]



Nervenarzt. 1994 Nov;65(11):780-6. Links
[Apolipoprotein E and Alzheimer dementia. Personal results and brief literature review]
[Article in German]
•    Forstl H,
•    Czech C,
•    Sattel H,
•    Geiger-Kabisch C,
•    Besthorn C,
•    Kreger S,
•    Monning U,
•    Hartmann T,
•    Masters C,
•    Beyreuther K.
Psychiatrische Klinik, Zentralinstitut fur Seelische Gesundheit, Mannheim.
The apolipoprotein E allele (Apo-E gene) status was determined in 147 individuals from a longitudinal study. 53 satisfied NINCDS-ADRDA criteria for probable or possible Alzheimer's disease (AD), 37 were non-demented healthy controls. 31 patients with AD had one or two Apo-E 4 alleles (phenotypes 1 x 4-2; 20 x 4-3; 10 x 4-4) compared with only 9 controls (8 x 4-3; 1 x 4-4). Within the AD group, patients homozygous for Apo-E 4 had an earlier onset of illness (7 of 10 cases were presenile) and more severe cognitive impairment at the time of examination after similar durations of illness as patients without Apo-E 4. This may reflect an influence of the Apo-E 4 gene dosage on the onset and course of illness, which is probably independent of chromosome 14 mutations.
PMID: 7816155 [PubMed - indexed for MEDLINE]



Nervenarzt. 1994 Sep;65(9):611-8. Links
[Frontal and temporal onset of brain atrophy. Clinical and instrumental findings]
[Article in German]
•    Forstl H,
•    Hentschel F,
•    Besthorn C,
•    Geiger-Kabisch C,
•    Sattel H,
•    Schreiter-Gasser U,
•    Bayerl JR,
•    Schmitz F,
•    Schmitt HP.
Psychiatrische Klinik, Zentralinstitut fur Seelische Gesundheit, Mannheim.
We report the cases of a 70-year old man with left temporal brain atrophy and of a 39-year-old man with neuropathologically verified frontal lobe degeneration (FLD) of Non-Alzheimer type. 10 patients with FLD collected during a prospective study on degenerative dementia had more severe volumetric brain changes and less severe quantitative band power changes than a group of matched patients with clinically diagnosed Alzheimer's disease.
PMID: 7991007 [PubMed - indexed for MEDLINE]



Acta Psychiatr Scand. 1994 May;89(5):335-40. Links
Organic factors and the clinical features of late paranoid psychosis: a comparison with Alzheimer's disease and normal ageing.
•    Forstl H,
•    Dalgalarrondo P,
•    Riecher-Rossler A,
•    Lotz M,
•    Geiger-Kabisch C,
•    Hentschel F.
Department of Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
The diagnostic allocation and aetiological basis of paranoid psychoses with late onset is controversial. We examined the clinical features of patients with a diagnosis of paranoid psychosis and we compared their cranial computed tomography (CT) scans and electroencephalographic (EEG) recordings with findings from matched samples of patients with Alzheimer's disease and non-demented elderly controls. During a 5-year period, 81 patients (15 men and 66 women) with a diagnosis of paranoid psychosis and onset after age 50 were referred to our Institute. They represent 5.4% of the patients older than 50 admitted during the same period. More than half of these patients had first-rank symptoms. The ventricles, anterior and sylvian fissures of the paranoid group were larger than in non-demented controls but smaller than in Alzheimer's disease. The posterior dominant alpha EEG rhythm was slower than in normal aging and faster than in Alzheimer's dementia. If paranoid patients with first-rank symptoms were distinguished from the ones without, the former had less severe brain atrophy and faster posterior dominant rhythm, although they received higher doses of neuroleptics. This could be explained by the existence of at least 2 subgroups of late paranoid psychosis: late-onset schizophrenia and organic paranoid syndrome, the former characterized by first-rank symptoms and less severe brain atrophy, the latter by more severe EEG and CT scan changes with a closer resemblance to degenerative brain disease.
PMID: 8067272 [PubMed - indexed for MEDLINE]



Electroencephalogr Clin Neurophysiol. 1994 Mar;90(3):242-5. Links
Comment in:
Electroencephalogr Clin Neurophysiol. 1994 Sep;91(3):232-3.
EEG coherence in Alzheimer disease.
•    Besthorn C,
•    Forstl H,
•    Geiger-Kabisch C,
•    Sattel H,
•    Gasser T,
•    Schreiter-Gasser U.
Zentralinstitut fur Seelische Gesundheit, Mannheim, Germany.
A novel approach is introduced to examine EEG coherence in different frequency bands of 17 locations from the 10-20 system. Fifty patients with clinically diagnosed Alzheimer's disease were compared with 42 age-approximated non-demented controls. We determined the average coherence between individual electrodes and all neighbouring electrodes. Coherence was decreased in the sample of demented patients and this effect was most pronounced in the frontal and central derivations of the theta, alpha and beta frequency bands. The results can be interpreted as the effects of neuronal loss and neocortical disconnection.
PMID: 7511505 [PubMed - indexed for MEDLINE]


Eur Arch Psychiatry Clin Neurosci. 1994;243(5):291-2. Links
Apolipoprotein E-4 gene dose in clinically diagnosed Alzheimer's disease: prevalence, plasma cholesterol levels and cerebrovascular change.
•    Czech C,
•    Forstl H,
•    Hentschel F,
•    Monning U,
•    Besthorn C,
•    Geiger-Kabisch C,
•    Sattel H,
•    Masters C,
•    Beyreuther K.
Center for Molecular Biology, Heidelberg, Germany.
The prevalence of the apolipoprotein E-4 allele (ApoE-4) was significantly higher in a referral population of 40 patients with clinically diagnosed Alzheimer's disease than in a sample of non-demented elderly controls (P < 0.01). The highest plasma cholesterol levels were found in demented patients homozygotic for Apo E-4, but no significant increases of glucose, triglycerides and thyroxine or of leuko-araiosis and brain infarcts were verified in this preliminary study.
PMID: 8172944 [PubMed - indexed for MEDLINE]


Psychopathology. 1994;27(3-5):194-9. Links
Delusional misidentification in Alzheimer's disease: a summary of clinical and biological aspects.
•    Forstl H,
•    Besthorn C,
•    Burns A,
•    Geiger-Kabisch C,
•    Levy R,
•    Sattel A.
Central Institute of Mental Health, Mannheim, Germany.
Delusional misidentification symptoms (DMS) are common in Alzheimer's disease (AD) and they are frequent sources of serious distress for patients and particularly caregivers. We observed DMS in around 30% of the patients with moderate to severe AD in two independent prospective studies; the Capgras type, phantom boarder, mirror and TV DMS were found most frequently. Patients with DMS showed increased EEG delta-power over the right hemisphere, their CT scans showed more severe right frontal lobe atrophy, and the number of their pyramidal cells in area CA1 was lower than in the patients without DMS. This may indicate that the development of DMS in AD can be promoted by certain patterns of brain degeneration which affect systems relevant to the recognition and updating of memories, while verbal skills may initially be left largely intact.
PMID: 7846237 [PubMed - indexed for MEDLINE]



Z Gerontol. 1993 Jul-Aug;26(4):275-9. Links
[Incidence and importance of "non-cognitive" symptoms in dementia of the Alzheimer type: productive psychotic symptoms, depressive disorders and behavioral disorders]
[Article in German]
•    Sattel H,
•    Geiger-Kabisch C,
•    Schreiter-Gasser U,
•    Besthorn C,
•    Forstl H.
Zentralinstitut fur Seelische Gesundheit, Sonderforschungsbereich 258, Mannheim.
A semi-structured interview was administered to the closest relatives of 50 patients with presenile or senile dementia of the Alzheimer type. The disturbances most frequently reported were: wandering/pacing (56%, cumulative percentage), aggressive behavior (44%) and - significantly related to more severe stages of dementia - apathy/loss of drive (58%), eating disturbances (46%) and disturbances of the sleep-waking cycle (32%). Depressive symptoms were observed in 58% of the patients, preferentially in the early stages of illness with preserved insight. Signs of paranoid delusions (46%), delusional misidentification (34%), visual (32%) and auditory hallucinations (16%) were encountered temporarily in a large number of patients. The importance of "non-cognitive" symptoms in Alzheimer's disease is underlined by their subjective significance for the caregivers.
PMID: 7692680 [PubMed - indexed for MEDLINE]



Acta Psychiatr Scand. 1993 Jun;87(6):395-9. Links
Psychotic features and the course of Alzheimer's disease: relationship to cognitive, electroencephalographic and computerized tomography findings.
•    Forstl H,
•    Besthorn C,
•    Geiger-Kabisch C,
•    Sattel H,
•    Schreiter-Gasser U.
Central Institute of Mental Health, Mannheim, Germany.
Thirty-one of 50 patients satisfying the NINCDS-ADRDA criteria of probable or possible Alzheimer's disease showed psychotic features during a 2-year observation period. Paranoid delusions were reported in 23 patients, delusional misidentification in 17, visual hallucinations in 16 and auditory hallucinations in 8. All of the 7 patients who died within the observation period had suffered from psychotic features even before the preterminal phase of illness. A faster progression of illness towards more severe stages of dementia was associated with paranoid delusions and hallucinations but not with delusional misidentification. We could not prove a significant influence of age, age of onset, cognitive performance, ventricular enlargement or the severity of quantitative electroencephalographic changes at initial examination on the course of illness. This may indicate that specific psychotic features and their potential organic substrate exert an effect on the progression of illness and on survival in Alzheimer's disease, which is not related to gross brain atrophy and generalized neurophysiological changes.
PMID: 8356890 [PubMed - indexed for MEDLINE]

Nervenarzt. 1992 Mar;63(3):163-8. Links
[Depressive disorders after cerebral infarct. Relations to infarct site, brain atrophy and cognitive deficits]
[Article in German]
•    Zerfass R,
•    Kretzschmar K,
•    Forstl H.
Psychiatrische Klinik, Zentralinstitut fur Seelische Gesundheit, Mannheim.
We studied the effects of the localisation and size of ischemic brain infarcts and the influence of potential covariates (gender, age, time since infarction, physical handicap, cognitive impairment, aphasia, cortical atrophy and ventricular size) on 'post-stroke depression'. During an 18-months period all patients who underwent a CT-scan at the Central Institute of Mental Health and who had a single unilateral ischemic hemisphere infarct were initially included. Patients with severe aphasia or cognitive impairment who could not communicate well enough for the administration of depression rating scales were excluded. This led to a selection bias towards larger infarct sizes in the right hemisphere. In order to overcome this potentially critical selection artefact all patients with infarct sizes over 23 cm2 and/or with 'mini Mental State Scores' under 20 were excluded. The data from the remaining 30 patients (mean age 68 years; 15 male; 13 left hemisphere infarcts were used for the analysis. Their scores on the Hamilton depression rating scale, the Zung self rating depression scale and the von Zerssen clinical self-rating depression scale correlated significantly with one another (r greater than 0.73; p less than 0.001). Backward stepwise regression analysis carried out on the covariates mentioned above demonstrated a significant relationship only between cognitive impairment or cortical atrophy and a higher depression score.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 1579174 [PubMed - indexed for MEDLINE]