Ulrich Seidl

The use of advanced tracking technologies for the analysis of mobility in Alzheimer's disease and related cognitive diseases

BackgroundOne of the more common behavioral manifestations of dementia-related disorders is severe problems with out-of-home mobility. Various efforts have been attempted to attain a better understanding of mobility behavior, but most studies are based on institutionalized patients and the assessment usually relies on reports of caregivers and institutional staff, using observational approaches, activity monitoring, or behavioral checklists. The current manuscript describes the research protocol of a project that measures mobility in Alzheimers disease and related cognitive disorders in an innovative way, by taking advantage of advanced tracking technologies.Methods/designParticipants are 360 demented persons, mildly cognitively impaired persons, and unimpaired controls aged ≥ 65 in Israel and Germany. Data regarding space-time activities will be collected via a GPS tracking kit for a period of 4 weeks in 3 waves (one year apart) with the same participants (using a repeated measures design). Participants will be interviewed by use of a battery of instruments prior to and following GPS data collection. Further, a family member will complete a questionnaire both before and after data tracking.Statistical analyses will strive to explain differences in mobility based on a wide range of socio-structural, clinical, affect-related and environmental variables. We will also assess the impact of the use of advanced tracking technology on the quality of life of dementia patients and care givers, as well as its potential as a diagnostic tool. Systematic assessment of ethical issues involved in the use of tracking technology will be an integral component of the project.DiscussionThis project will be able to make a substantial contribution to basic as well as applied and clinical aspects in the area of mobility and cognitive impairment research. The innovative technologies applied in this study will allow for assessing a range of dimensions of out-of-home mobility, and provide better quality data.

Reduced cerebral glucose metabolism in patients at risk for Alzheimer's disease

While significantly reduced glucose metabolism in fronto-temporo-parietal and cingulate cortices has been demonstrated in Alzheimers disease (AD) compared with controls, cerebral glucose metabolism in patients with mild cognitive impairment who subsequently develop AD is less well-defined. In the present study we measured cerebral glucose metabolism by positron emission tomography (PET) with (18)F-2-fluoro-2-deoxy-D-glucose in 14 patients with aging-associated cognitive decline (AACD), 44 patients with AD, and 14 healthy control subjects at baseline. The AACD patients were clinically followed up, and conversion to AD was determined. Compared with controls, AACD patients had significantly reduced glucose metabolism in the right precuneus, posterior cingulate, right angular gyrus, and bilateral middle temporal cortices, while the respective deficits were more pronounced in AD patients and also involved the frontal cortices. AACD patients who subsequently converted to AD (AACD-converters) showed more extended metabolic changes which also involved the frontal and temporal cortices, right cingulate gyrus, right thalamus, and bilateral precuneus.

The cerebellum in mild cognitive impairment and Alzheimer’s disease – A structural MRI study

Neuropathological research consistently revealed the cerebellum to undergo degenerative changes in Alzheimers disease (AD). Whether these alterations affect cerebellar morphology in vivo has not yet been investigated in a comprehensive way. Magnetic resonance imaging was performed in 20 patients with AD, 20 with mild cognitive impairment (MCI), and 20 healthy controls. By manual tracing the cerebellum was divided in four substructures (anterior lobe, superior posterior lobe, inferior posterior lobe and corpus medullare, respectively) on each hemisphere. Posterior cerebellar lobes were significantly smaller in AD patients when compared to healthy controls. In the AD group, atrophy of the posterior cerebellar regions was associated with poorer cognitive performance. Our findings lend further support for cerebellar involvement in AD.

P50 gating deficit in Alzheimer dementia correlates to frontal neuropsychological function

BACKGROUND Cognitive inhibition processes were found to be deficient early in the clinical course of Alzheimers disease (AD). The inhibition of redundant information is a precondition for efficient cognitive processing and presumably modulated by prefrontal attentional networks. Deficits in the suppression of the evoked potential P50 response to paired clicks are well known in schizophrenic patients and undergo cholinergic modulation. In this study, we aimed to investigate inhibitory gating deficits of P50 in AD and their relation to neuropsychological measures. METHOD P50 suppression was assessed in 19 AD-patients in comparison to a young and elderly control group (n=17 each) and related to MMSE and specific neuropsychological assessments. RESULTS Patients showed reduced sensory gating compared to healthy elderly (p<0.021) and exhibited significantly higher N40-P50-amplitudes. There were no age or gender effects in controls. Frontal neuropsychological tests (TMT-B, verbal fluency) and working memory requiring inhibition, but not declarative memory functions, were significantly correlated with inhibitory gating and test amplitude in both, AD-patients and controls. CONCLUSIONS The results support an early inhibitory deficit interfering with executive functions and working memory in AD independent from physiological aging. P50 gating might be applicable as a marker for inhibition deficits and thereby be important for prognosis estimation.

MRI-Derived Atrophy of the Olfactory Bulb and Tract in Mild Cognitive Impairment and Alzheimer's Disease

There is increasing histopathological evidence that the olfactory bulb and tract (OBT) is a primary focus of neurodegenerative changes in Alzheimers disease (AD). Correspondingly, high-resolution magnetic resonance imaging revealed significant atrophy of the OBT in manifest AD. Whether these alterations are already present in mild cognitive impairment, the assumed preclinical stage of AD, has not been investigated yet. OBT volumes were assessed by manual tracing in 29 patients with mild cognitive impairment, 27 patients with probable AD, and 30 healthy controls. In a second step, voxel based morphometry was used to investigate the potential association between OBT atrophy and morphological changes in other brain regions. Patients had significantly lower OBT volumes when compared to controls, with atrophy being most prominent in the AD group. In addition, OBT atrophy was associated with a decreased medial temporal lobe (MTL) gray matter density bilaterally. Our findings indicate that neurodegeneration in OBT and MTL regions is linked and suggest that OBT volume might be a surrogate marker in AD.

Morphological Cerebral Correlates of CERAD Test Performance in Mild Cognitive Impairment and Alzheimer's Disease

The objective of this study was to investigate the association between structural cerebral changes and neuropsychological deficits in mild cognitive impairment (MCI) and Alzheimers disease (AD). Sixty patients with MCI, 34 patients with mild to moderate AD, and 32 healthy controls underwent both extensive neuropsychological assessment (CERAD test battery) and high-resolution structural magnetic resonance imaging. We used optimized voxel based morphometry to investigate (i) differences in gray matter density between the three aforementioned groups and (ii) the putative relations of CERAD test performance with atrophic brain changes. When compared to the healthy controls, the AD patients and, to a lesser extent, patients with MCI showed significant density losses predominantly in the medial temporal lobe. Deficits in verbal fluency and word finding were significantly correlated with left fronto-temporal and left temporal (including hippocampal) changes, respectively. Decreased scores in immediate and delayed recall and in delayed recognition were associated with several cortical and subcortical sites including the parahippocampal and posterior cinguli gyri, the right thalamus, and the right hippocampus, whereas deficits in constructional praxis and constructional praxis recall referred to sites in the left thalamus and cerebellum, and the temporal cortices (bilaterally), respectively. Our findings lend further support for medial temporal lobe degeneration in MCI and AD and demonstrate that cognitive deficits as assessed on the CERAD do not simply refer to specific changes in discrete cerebral sites but rather reflect morphological alterations in widespread networks.

Das Heidelberger Instrument zur Erfassung von Lebensqualität bei Demenz (H.I. L.DE.)

ZusammenfassungDer Beitrag beschreibt den theoretischen Hintergrund und das methodische Vorgehen der H.I.L.DE.-Studie. In diesem Forschungsprojekt soll ein umfassendes Instrumentarium zur Messung von Lebensqualität bei demenzkranken Heimbewohnern entwickelt und erprobt werden. Ausgehend von der Annahme, dass auch in fortgeschrittenen Stadien der Erkrankung Emotionen erlebt und auf der Grundlage des mimischen Ausdrucks gedeutet werden können, wurden in Zusammenarbeit mit 11 Pflegeeinrichtungen unterschiedlicher Trägerschaft drei Stichproben von Untersuchungsteilnehmern gezogen: 121 demenzkranke Heimbewohner, 97 Pflegekräfte und 101 Angehörige haben an der ersten Projektphase teilgenommen. Bei der operationalen Definition von Lebensqualität geht das H.I.L.DE.-Projekt von einer Differenzierung der folgenden acht Dimensionen von Lebensqualität aus: räumliche Umwelt, soziale Umwelt, Betreuungsqualität, Verhaltenskompetenz, medizinisch-funktionaler Status, kognitiver Status, Psychopathologie und Verhaltensauffälligkeiten sowie subjektives Erleben und emotionale Befindlichkeit. Die Messung dieser acht Dimensionen beruht auf medizinischen Untersuchungen, Interviews mit Bewohnern, Pflegekräften und Angehörigen, ökopsychologischen Einschätzungen räumlicher Umwelt und Analysen von Pflegedokumenten. Erste Ergebnisse der H.I.L.DE.-Studie werden zur Illustration der Potenziale eines derart umfassenden methodischen Ansatzes genutzt.SummaryThe contribution is intended to describe the theoretical background and measurement approach of H.I.L.DE., a research project aimed to develop and validate a comprehensive assessment of quality of life in nursing home residents suffering from dementia. Proceeding from the assumption that emotions are felt even in advanced stages of dementia and can be interpreted on the basis of peoples’ mimic expressions, three samples of participants were recruited from 11 nursing homes of varying maintenance: 121 nursing home residents suffering from dementia, 97 professional caregivers and 101 relatives participated in the first wave of this study. Operational definition of quality of life in H.I.L.DE. proceeds from the differentiation of eight dimensions of quality of life: physical environment, social environment, quality of care, behavioral competence, medical and functional status, cognitive status, psychopathology and behavior disturbances, and subjective experiences of physical and social environment and emotional well-being. Measures of the eight dimensions involve data from medical examination, interviews with residents, professional caregivers and relatives, ecopsychological assessment of physical environment and analysis of care documents. First results from the H.I.L.DE.-study are used as an illustration of the potentials of such a comprehensive approach to the measurement of quality of life.

[The Heidelberg instrument for the assessment of quality of life in dementia (H. I. L. DE.)--dimensions of quality of life and methods of organization].

ZusammenfassungDer Beitrag beschreibt den theoretischen Hintergrund und das methodische Vorgehen der H.I.L.DE.-Studie. In diesem Forschungsprojekt soll ein umfassendes Instrumentarium zur Messung von Lebensqualität bei demenzkranken Heimbewohnern entwickelt und erprobt werden. Ausgehend von der Annahme, dass auch in fortgeschrittenen Stadien der Erkrankung Emotionen erlebt und auf der Grundlage des mimischen Ausdrucks gedeutet werden können, wurden in Zusammenarbeit mit 11 Pflegeeinrichtungen unterschiedlicher Trägerschaft drei Stichproben von Untersuchungsteilnehmern gezogen: 121 demenzkranke Heimbewohner, 97 Pflegekräfte und 101 Angehörige haben an der ersten Projektphase teilgenommen. Bei der operationalen Definition von Lebensqualität geht das H.I.L.DE.-Projekt von einer Differenzierung der folgenden acht Dimensionen von Lebensqualität aus: räumliche Umwelt, soziale Umwelt, Betreuungsqualität, Verhaltenskompetenz, medizinisch-funktionaler Status, kognitiver Status, Psychopathologie und Verhaltensauffälligkeiten sowie subjektives Erleben und emotionale Befindlichkeit. Die Messung dieser acht Dimensionen beruht auf medizinischen Untersuchungen, Interviews mit Bewohnern, Pflegekräften und Angehörigen, ökopsychologischen Einschätzungen räumlicher Umwelt und Analysen von Pflegedokumenten. Erste Ergebnisse der H.I.L.DE.-Studie werden zur Illustration der Potenziale eines derart umfassenden methodischen Ansatzes genutzt.SummaryThe contribution is intended to describe the theoretical background and measurement approach of H.I.L.DE., a research project aimed to develop and validate a comprehensive assessment of quality of life in nursing home residents suffering from dementia. Proceeding from the assumption that emotions are felt even in advanced stages of dementia and can be interpreted on the basis of peoples’ mimic expressions, three samples of participants were recruited from 11 nursing homes of varying maintenance: 121 nursing home residents suffering from dementia, 97 professional caregivers and 101 relatives participated in the first wave of this study. Operational definition of quality of life in H.I.L.DE. proceeds from the differentiation of eight dimensions of quality of life: physical environment, social environment, quality of care, behavioral competence, medical and functional status, cognitive status, psychopathology and behavior disturbances, and subjective experiences of physical and social environment and emotional well-being. Measures of the eight dimensions involve data from medical examination, interviews with residents, professional caregivers and relatives, ecopsychological assessment of physical environment and analysis of care documents. First results from the H.I.L.DE.-study are used as an illustration of the potentials of such a comprehensive approach to the measurement of quality of life.

Out-of-Home Behavior and Cognitive Impairment in Older Adults Findings of the SenTra Project

This study explores differences in the out-of-home behavior of community-dwelling older adults with different cognitive impairment. Three levels of complexity of out-of-home behavior were distinguished: (a) mostly automatized walking behavior (low complexity), (b) global out-of-home mobility (medium complexity), and (c) defined units of concrete out-of-home activities, particularly cognitively demanding activities (high complexity). A sample of 257 older adults aged 59 to 91 years (M = 72.9 years, SD = 6.4 years) included 35 persons with early-stage Alzheimer’s disease (AD), 76 persons with mild cognitive impairment (MCI), and 146 cognitively healthy persons (CH). Mobility data were gathered by using a GPS tracking device as well as by questionnaire. Predicting cognitive impairment status by out-of-home behavior and a range of confounders by means of multinomial logistic regression revealed that only cognitively demanding activities showed at least a marginally significant difference between MCI and CH and were highly significant between AD and CH.

Autobiographical Memory Deficits in Alzheimer's Disease

Autobiographical memory comprises memories of ones own past that are characterized by a sense of subjective time and autonoetic awareness. Although autobiographical memory deficits are among the major complaints of patients with dementia, they have rarely been systematically assessed in mild cognitive impairment and Alzheimers disease. We therefore investigated semantic and episodic aspects of autobiographical memory for remote and recent life periods in a sample of 239 nursing home residents (165 in different stages of Alzheimers disease, 33 with mild cognitive impairment, and 41 cognitively unimpaired) with respect to potential confounders. Episodic autobiographical memories, especially the richness of details, were impaired early in the course of Alzheimers disease or even in the preclinical phase, while semantic memories were spared until moderate stages, indicating a dissociation between both memory systems. The examination of autobiographic memory loss can facilitate the clinical diagnosis of Alzheimers disease.