Biomedical subjects

Lutz Frölich

Publications and source records attributed to Lutz Frölich.

15 recordsLinked to original sources

PubMed2006

Occupational exposure to low frequency magnetic fields and dementia: a case-control study.

BACKGROUND: Several studies point to a potential aetiological relevance to dementia of exposure to low-frequency magnetic fields, but the evidence is inconclusive. OBJECTIVE: To further examine the relationship between low frequency magnetic fields and dementia. METHODS: From 23 general practices, 195 patients with dementia were recruited. Of these, 108 had possible Alzheimer's disease, 59 had possible vascular dementia and 28 had secondary or unclassified dementia. A total of 229 controls were recruited: 122 population controls and 107 ambulatory patients free from dementia. Data were gathered in a structured personal interview; in cases, the interview was administered to the next of kin. Exposure to low-frequency electromagnetic fields was assessed by expert rating. To identify occupations suspected to be associated with dementia, major occupations were a priori formed. Odds ratios were calculated using logistic regression, to control for age, region, sex, dementia in parents and smoking. RESULTS: Exposure to magnetic fields was not significantly associated with dementia; restriction of the analysis to cases with possible Alzheimer's disease or possible vascular dementia did not lead to statistically significant results. We found an increased risk of dementia in blue-collar occupations (electrical and electronics workers, metal workers, construction workers, food and beverage processors and labourers). CONCLUSIONS: Our study does not support a strong association between occupational exposure to low-frequency magnetic fields and dementia. Further studies should consider the relationship between blue-collar work and the late development of dementia.

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PubMed2006

Insulin effects on CSF norepinephrine and cognition in Alzheimer's disease.

We assessed the effects of induced hyperinsulinemia on plasma and cerebrospinal fluid (CSF) levels of norepinephrine (NE) and on cognition for patients with Alzheimer's disease (AD) and normal older adults. For normal adults, insulin increased plasma and CSF NE levels; also, recall for paraphrased details of a story improved as CSF NE levels increased. Mental control was positively correlated with CSF levels of NE for patients. These findings demonstrate that raising peripheral insulin levels can modulate CNS NE levels and suggest that insulin-stimulated increases in NE may modulate cognitive functions.

Aged↗

PubMed2005

Memory for performed actions in dementia of Alzheimer type: further evidence for a global semantic memory deficit.

Findings in patients with dementia of the Alzheimer type (AD patients) concerning the enactment effect, i.e. reaching a better memory performance after encoding actions by performing them in contrast to encoding them by reading, are ambiguous. In order to get more insight into memory deterioration in patients suffering from AD, an experimental study was run. Patients with mild-to-moderate AD (n = 23) and healthy elderly control persons (n = 20) took part. They had to encode actions verbally as well as enactively. Memory performance was tested by using recognition judgments instead of the predominating free recall. The AD patients showed no enactment effect and a rate of false alarm judgments that was more than twice as high as found in healthy elderly controls. This enactive encoding failure may be indicative of memory deficits underlying the conceptual system of action representations.

Aged↗

PubMed2005

Diagnostic value of FDG-PET and HMPAO-SPET in patients with mild dementia and mild cognitive impairment: metabolic index and perfusion index.

OBJECTIVE: The diagnostic potential of F-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET) and technetium-99m hexamethylpropylene amine oxime single-photon emission tomography (SPET) in early detection and differential diagnosis of early dementia was evaluated including a comparison of metabolic and perfusion indices (PI). METHODS: Twenty-four patients with initial clinical suspicion of beginning dementia were examined, 12 of them with mild cognitive impairment. All patients underwent SPET and PET within 2 weeks. Data were compared with the final clinical diagnosis at follow-up - 9 with Alzheimer's disease (AD), 1 with frontotemporal dementia, 1 with vascular dementia (VD), 7 with mixed type of dementia (MIX) and 6 without any type of dementia. Metabolic indices (MI) and PI were compared with each other. The regional cerebral blood flow difference (rCBFdiff) calculated as local uptake difference between the right and left hemisphere was measured for patients with VD and MIX. RESULTS: PET showed higher sensitivity and specificity in identifying the different types of early dementia (44--91 and 78--89%, respectively) than SPET (11--64 and 79--89%, respectively), especially in detecting AD (sensitivity 44%, specificity 83%) and MIX (sensitivity 71%, specificity 78%). Especially in patients with mild cognitive impairment, PET was the superior imaging modality for predicting dementia. Using PET, dementia could be excluded in all patients who did not develop dementia during the follow-up. In all patients, a weak correlation between PI and MI was observed (rho=0.64, p<0.002). The rCBFdiff in patients with VD and MIX ranged from 7 to 37%. CONCLUSION: In this study on patients with initial suspicion of beginning dementia who underwent both imaging modalities, PET and SPET, PET was the superior imaging method, especially in the detection of early AD or MIX.

Aged↗

PubMed2005

Nicotine use in suicides: a case-control study.

PURPOSE: Despite of higher rates of substance-related disorders in psychiatric patients and suicides than in the general population, there is no clear specificity to the relationship between nicotine use and other psychiatric disorders for suicide risk. METHODS: One hundred and sixty-three suicides (mean age 49.8 +/- 19.3 years; 64.4% males; using psychological autopsy method) and 396 control persons (mean age 51.6 +/- 17.0 years; 55.8% males) were assessed with a standardised semi-structured interview including SCID-I and SCID-II (for DSM-IV). Suicides and controls were compared in terms of nicotine consumption and psychiatric disorders. Logistic regression was used to evaluate the interactions of tobacco consumption with psychiatric disorders. RESULTS: Suicides were significantly more often current smokers and heavy users of cigarettes (> 20 cigarettes per day; P < 0.001, each). Alcohol dependence, other axis I disorders than substance-related disorders, and cluster B personality disorder(s) remained independent predictors for suicide in both genders, current nicotine consumption only in men (OR = 2.6, 95% CI 1.3-5.2). DISCUSSION AND CONCLUSIONS: In males, but not in females, nicotine consumption contributed to risk of completed suicide after control for psychiatric disorders and has to be considered as independent risk factor for suicide.

Autopsy↗

PubMed2004

Concordance of DSM-IV Axis I and II diagnoses by personal and informant's interview.

The validity and reliability of using psychological autopsies to diagnose a psychiatric disorder is a critical issue. Therefore, interrater and test-retest reliability of the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders and the usefulness of these instruments for the psychological autopsy method were investigated. Diagnoses by informant's interview were compared with diagnoses generated by a personal interview of 35 persons. Interrater reliability and test-retest reliability were assessed in 33 and 29 persons, respectively. Chi-square analysis, kappa and intraclass correlation coefficients, and Kendall's tau were used to determine agreement of diagnoses. Kappa coefficients were above 0.84 for substance-related disorders, mood disorders, and anxiety and adjustment disorders, and above 0.65 for Axis II disorders for interrater and test-retest reliability. Agreement by personal and relative's interview generated kappa coefficients above 0.79 for most Axis I and above 0.65 for most personality disorder diagnoses; Kendall's tau for dimensional individual personality disorder scores ranged from 0.22 to 0.72. Despite of a small number of psychiatric disorders in the selected population, the present results provide support for the validity of most diagnoses obtained through the best-estimate method using the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders. This instrument can be recommended as a tool for the psychological autopsy procedure in post-mortem research.

Adjustment Disorders↗

PubMed2004

Combination therapy in Alzheimer's disease: a review of current evidence.

Treating dementia has become a major challenge in clinical practice. Presently, acetylcholinesterase inhibitors are the first-line drugs in the treatment of Alzheimer's disease (AD). These options are now complemented by memantine, which is approved for the treatment of moderate-to-severe AD. Altogether, a minimum of six agent classes already exist, all of which are approved for clinical use and are either already being tested or ready for phase III clinical trials for the treatment of AD. These include cholinesterase inhibitors, blockers of the NMDA receptor, antioxidants or blockers of oxidative deamination (including Gingko biloba), anti-inflammatory agents, neurotrophic factors (including hormone replacement therapy and drugs acting on insulin signal transduction) and antiamyloid agents (including cholesterol-lowering therapy). These approaches hold promise for disease modification and have a potential to be used as combination therapy for cognitive enhancement. Presently, only nine clinical studies have been published that have investigated the effects of a combination regimen on cognitive performance or AD. Among those, one study was conducted in elderly cognitively intact persons; the others involved patients with AD. Only five of the treatment studies followed a randomised, controlled design. Not all studies favoured the superior efficacy of combination therapy over monotherapy. Some studies, however, showed some evidence for synergistic combination effects of symptomatic therapy, including delay or prevention of disease progression in AD patients. In addition, six studies investigated the effects of AChE inhibitor in combination with antipsychotic or antidepressant therapy on behavioural aspects of AD symptomatology. In four of those studies there were indications that combination therapy had greater efficacy over monotherapy. The treatment of AD patients requires optimised options for all stages of illness based on the available drugs. There is a great need for further well designed studies on combination therapy in AD.

Alzheimer Disease↗

PubMed2004

Targets of antidementive therapy: drugs with a specific pharmacological mechanism of action.

Diagnosis and therapy of dementia have made considerable progress in recent years. Drugs have been developed which improve cognitive performance, delay the loss of abilities of daily living and prevent early nursing home placement in a considerable number of patients. With the various pharmacological and non-pharmacological approaches, effective treatment options of AD are available at present and the therapeutic potential will even increase in future. Thus, the treatment of dementia should more focused and explicit in its goals for the doctor, the patient and the relatives. Therapeutic targets must be defined on the basis of the individual needs and deficits and with regard to different levels of the disease process. Ideally, treatment should always aim at an etiological and/or a pathophysiological level. At present, however, aiming at the neurotransmitter level, the core syndrome of cognitive deficits can be approached by treatment options. Further therapeutic targets can be defined on the level of activities of daily living, following a resource focused approach, as well as on the level of behavioral disturbances. Additional therapeutic targets should be seen under a humanitarian or palliative perspective. And finally, family members are also targets for therapy in dementia, even if such therapy is not directed towards the demented patient. All these treatment targets have to be evaluated and adapted under the perspective of time because prominent symptoms in AD change considerably with disease progression. Selection and adaptation of medication becomes easier if such targets are considered and if therapeutic effects are monitored target-specifically.

Alzheimer Disease↗

PubMed2003

Brain metabolism in Alzheimer disease and vascular dementia assessed by in vivo proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer's disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification.

Aged↗

PubMed2003

An observational clinical study of the efficacy and tolerability of donepezil in the treatment of Alzheimer's disease.

An open-label, observational Post-Marketing Surveillance (PMS) study was undertaken in Germany to examine the efficacy and tolerability of donepezil in routine clinical practice. Alzheimer's disease (AD) patients were treated with donepezil (5 or 10 mg once daily) and observed for a period of approximately 3 months. Study assessments included the Mini-Mental State Examination (MMSE), the Nurses' Observation Scale for Geriatric Patients (NOSGER), and adverse events (AEs). A total of 2,092 patients (mean age 73.0 years; mean +/- SD MMSE score 17.8 +/- 5.8) were included in the efficacy assessments. MMSE and NOSGER scores showed statistically significant improvements in the total patient population and in the subpopulations with severe AD or AD with concomitant Parkinsonian symptoms (ADPS cohort). AEs were reported in a total of 12% of patients and were mostly due to peripheral cholinergic effects. In this observational PMS study, donepezil was shown to be an effective and well-tolerated therapy in the overall patient population, in patients with severe AD, and in the ADPS cohort.

Activities of Daily Living↗

PubMed2003

Olfactory function in mild cognitive impairment and Alzheimer's disease: an investigation using psychophysical and electrophysiological techniques.

OBJECTIVE: To clarify the olfactory deficit hypothesis regarding Alzheimer's disease, the authors compared olfactory function in patients with Alzheimer's disease, subjects with mild cognitive impairment, and healthy comparison subjects. METHOD: Olfactory function of 14 patients with mild Alzheimer's disease, eight subjects with mild cognitive impairment, and eight healthy age-matched comparison subjects was assessed with both psychophysical tests and olfactory event-related potentials. RESULTS: Group comparison of the psychophysical test results showed a significant main effect of diagnosis for odor detection threshold, odor discrimination, and odor identification. These results correlated only partially with those obtained from olfactory event-related potentials. Seven Alzheimer's disease patients and four with mild cognitive impairment showed no olfactory event-related potentials, suggesting hyposmia, while all comparison subjects had clearly discernible responses. Patients with Alzheimer's disease were significantly more likely to be nonresponders. In the four Alzheimer's disease patients and four subjects with mild cognitive impairment who had clear electrophysiological responses, amplitudes and latencies of the various event-related potential components were normal, i.e., similar to those of the comparison subjects, although 12 of the 14 Alzheimer's disease patients and seven of the eight mildly impaired subjects were classified as functionally anosmic with psychophysical methods. CONCLUSIONS: The electrophysiological results confirm prior findings of olfactory dysfunction in patients with Alzheimer's disease and preclinical Alzheimer's disease. Investigations of larger study groups with detailed cognitive examination and postmortem diagnosis may resolve the intriguing possibility of early diagnosis and discrimination of Alzheimer's disease subtypes through chemosensory event-related potentials in addition to existing biomarkers.

Aged↗

PubMed2003

Impact of aging: sporadic, and genetic risk factors on vulnerability to apoptosis in Alzheimer's disease.

The identification of specific genetic (presenilin-1 [PS1] and amyloid precursor protein [APP] mutations) and environmental factors responsible for Alzheimer's disease (AD) has revealed evidence for a shared pathway of neuronal death. Moreover, AD-specific cell defects may be observed in many other nonneuronal cells (e.g., lymphocytes). Thus, lymphocytes may serve as a cellular system in which to study risk factors of sporadic, as well as genetic AD in vivo. The aim of our present study was to clarify whether lymphocytes bearing genetic or sporadic risk factors of AD share an increased susceptibility to cell death. Additionally we examined whether a cell typespecific vulnerability pattern was present and how normal aging, the main risk factor of sporadic AD, contributes to changes in susceptibility to cell death. Here, we report that lymphocytes affected by sporadic or genetic APP and PS1 AD risk factors share an increased vulnerability to cell death and exhibit a similar cell type-specific pattern, given that enhanced vulnerability was most strongly developed in the CD4+ T-cell subtype. In this paradigm, sporadic risk factors revealed the highest impact on cell type-specific sensitivity of CD4+ T cells to apoptosis. In contrast, normal aging results in an increased susceptibility to apoptosis of both, CD4+ and CD8+ T cells.

Age Factors↗

PubMed2002

Psychometric properties of Clock Drawing Test and MMSE or Short Performance Test (SKT) in dementia screening in a memory clinic population.

OBJECTIVE: To evaluate five different scoring methods of the Clock Drawing Test (CDT) and to examine whether a combination of Mini Mental State Examination (MMSE) or Short Performance Test (Syndrom Kurz Test, SKT), respectively, with CDT can be used for cognitive screening. METHODS: Retrospective blinded analysis of clock drawing performance using five scoring methods (Shulman et al. (1986), Sunderland et al. (1989), Wolf-Klein et al. (1989), Watson et al. (1997), Manos (1997)). A Memory Clinic at an academic psychiatric hospital (University of Frankfurt am Main, Germany). 123 consecutive patients (79 dementia patients, 44 controls). Inter-rater reliability and correlation of five different scoring methods of the CDT with established psychometric tests. Sensitivity and specificity of all five CDT's using the original and modified cut-off scores. Sensitivity, specificity and positive and negative predictive value of a combination of the CDT with MMSE and SKT, respectively. RESULTS: All scoring methods of the CDT showed a highly significant interrater reliability (0.82 to 0.94). Correlation with the MMSE and the SKT was also significant (p < 0.01) for all five CDTs. Highest sensitivity was achieved by the Shulman scoring method (81% sensitivity, specificity 79%). Sensitivity of all scoring methods could be improved up to 89% by modifying the originally proposed cut-off scores at the cost of lower specificity. By combining the CDT with the MMSE or the SKT, respectively, the sensitivity of each of the tests could be improved to 92% (SKT and Shulman scale). In patients with mild dementia (GDS 3), a combination of the Shulman Scale with the SKT (92%) and the MMSE (75%) achieved the highest sensitivity. CONCLUSIONS: The CDT in combination with the MMSE or SKT is an easily administered, non threatening and highly sensitive screening test for dementia in the setting of a memory clinic.

Adult↗

PubMed2002

[Difficulties in the evaluation of depressive symptoms in patients with dementia].

Depressive symptoms are often found in dementia (up to 86 %). Therefore, adequate treatment is necessary. Depressive symptoms appear significantly more often in vascular dementia than in dementia in Alzheimer's disease, but severity and profile of depressive symptomatology are independent of the etiology of dementia. The aim of this review is to help clinicians to select appropriate psychometric instruments to identify and measure depressive symptomatology in dementia. Frequently used scales are described, e.g. the Dementia Mood Assessment Scale and the Cornell Scale for Depression in Dementia - specific scales developed for rating severity of depression in dementia - and the Geriatric Depression Screening Scale. Methodological problems and limitations of psychopathological assessment in dementia caused by restriction of self-report, information gathered by collateral sources, manifestations of age and interference of somatic symptoms are discussed.

Aged↗

PubMedDate not supplied

Association between the psychosocial network and dementia--a case-control study.

In a case-control study, we investigated the possible etiological relevance to dementia of psychosocial network factors, such as marital status, confidants and close relatives, sports activities, cultural activities, club membership; and education. In 23 general practices we recruited 195 patients with dementia. Of these, 108 were suffering from possible Alzheimer's disease, 59 from possible vascular dementia and 28 from secondary or unclassified dementia. A total of 229 control subjects was recruited: 122 population controls and 107 dementia-free ambulatory patients. Data were gathered in a structured personal interview and analyzed using logistic regression, to control for age, region, sex, dementia in parents, education and smoking. There were significantly decreased odds ratios for the number of confidants, sports activities, and cultural activities at age 30, at age 50 and at 10 years before data collection. When all psychosocial network factors were included simultaneously in the logistic regression model, these factors remained statistically significant, indicating independent effects. Restriction of the analysis to cases with possible Alzheimer's disease or to cases with possible vascular dementia led to similar results. Adjustment for the psychosocial network neutralized the otherwise protective effect of education for dementia of any type and for possible vascular dementia. In keeping with the results from recently published studies, these results support a protective role for the psychosocial network-especially for the number of confidants and for sports and cultural activities-in the etiology of dementia.

Aged↗