Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis i... more Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis in blood. Here we measured PCT by immunoassay in CSF and matched serum/plasma samples of controls and patients with different primary dementia disorders and acute neuroinflammation. PCT in CSF was significantly increased in patients with probable Alzheimer's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and acute neuroinflammation (encephalitis, meningitis) compared to non-demented controls. In contrast, PCT levels in matched plasma samples were normal in dementia groups, but elevated in meningitis/encephalitis. Our results indicate a central production of PCT and suggest PCT as a valuable marker candidate for the monitoring of dementia and acute neuroinflammation.
While we may not be able to find a cure for Alzheimer's disease (AD) in the near future, seve... more While we may not be able to find a cure for Alzheimer's disease (AD) in the near future, several drugs presently in trials have shown promise as possible modifiers of disease progression. However, we may not be able to demonstrate efficacy due to issues of recruitment, retention, site-to-site variability, and other methodological issues. It is thus incumbent on the scientific community to find solutions to these problems, particularly as the field moves toward preventing illness or treating the disease in its prodromal stages, where these methodological issues will become even more critical. We need to better understand why participants agree or refuse to enter drug trials, and why both primary care physicians and Alzheimer's specialists agree or refuse to involve their patients. We also need to quantify the impact of requiring imaging studies, extensive questionnaires, cognitive testing, and lumbar punctures on recruitment and retention. With these concerns in mind, an inte...
In the earliest clinical stages of Alzheimer's Disease (AD), when symptoms are mild, clinical... more In the earliest clinical stages of Alzheimer's Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the pr...
The 7th annual meeting of the memory clinics of Germany, Switzerland and Austria in March 2002 in... more The 7th annual meeting of the memory clinics of Germany, Switzerland and Austria in March 2002 in Göttingen, Germany was an optimal opportunity to make an inventory about the state of the art in diagnostic and therapy of dementia and mild cognitive impairment in German-speaking memory clinics. Several problems were discussed including difficulties in 1) diagnosis of patients with aphasia or foreign patients, 2) handling of demented patients without a caregiver, 3) psychological support for patients, who have been diagnosed in a very early stage, 4) misunderstandings between general practitioners, neurologists and psychiatrists in private practice on the one hand and the memory clinics on the other hand, 5) recommendations for prevention of dementia, 6) recommendations concerning dementia and car driving and 7) questions of genetic counselling. The following paper is a summary of the results of a workshop in Göttingen and gives practical recommendations based on the experiences of th...
The CERAD neuropsychological test battery is becoming the standard measure for screening cognitiv... more The CERAD neuropsychological test battery is becoming the standard measure for screening cognitive deficits associated with dementia. The seven subtests of the CERAD battery (Mini-Mental State Examination or MMSE, verbal fluency, Modified Boston Naming Test or MBNT, construction ability, learning of word lists, recall, and recognition), a short test of crystallized intelligence (vocabulary test or WST), and a simple test of visuo-motor tracking (number relation test-G or ZVT-G) were applied to 30 healthy control subjects, 49 depressed patients, and 98 mildly to severely demented patients. All subtests of the CERAD battery separated controls from mildly demented patients. Overall, depressed patients scored between controls and mildly demented patients. Score differences between depressed patients and mildly demented patients were significant for MMSE, learning and recall of the word list, verbal fluency, and MBNT. This paper contains a profile sheet for the CERAD battery developed ac...
Diagnosis upon autopsy of patients suffering from Alzheimer's disease (AD) and other dementin... more Diagnosis upon autopsy of patients suffering from Alzheimer's disease (AD) and other dementing disorders is required to confirm or reject the clinical diagnosis. Autopsy studies are crucial to validate diagnostic criteria as well as to gain new insights in AD epidemiology, genetics, pathophysiology and therapy. The current decrease of autopsy rates leads to a lack of research which is essential to improve diagnosis and therapy of AD. Only the cooperation between physicians in memory-clinics, general practitioners and neuropathologists can prevent this unfortunate development. Brain-Net, the German brain bank, is a unique approach to provide organisational support for such a concerted action.
Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics... more Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD.
Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis i... more Procalcitonin (PCT) is an established marker for severe systemic bacterial infection and sepsis in blood. Here we measured PCT by immunoassay in CSF and matched serum/plasma samples of controls and patients with different primary dementia disorders and acute neuroinflammation. PCT in CSF was significantly increased in patients with probable Alzheimer's disease, vascular dementia, dementia with Lewy bodies, frontotemporal dementia and acute neuroinflammation (encephalitis, meningitis) compared to non-demented controls. In contrast, PCT levels in matched plasma samples were normal in dementia groups, but elevated in meningitis/encephalitis. Our results indicate a central production of PCT and suggest PCT as a valuable marker candidate for the monitoring of dementia and acute neuroinflammation.
While we may not be able to find a cure for Alzheimer's disease (AD) in the near future, seve... more While we may not be able to find a cure for Alzheimer's disease (AD) in the near future, several drugs presently in trials have shown promise as possible modifiers of disease progression. However, we may not be able to demonstrate efficacy due to issues of recruitment, retention, site-to-site variability, and other methodological issues. It is thus incumbent on the scientific community to find solutions to these problems, particularly as the field moves toward preventing illness or treating the disease in its prodromal stages, where these methodological issues will become even more critical. We need to better understand why participants agree or refuse to enter drug trials, and why both primary care physicians and Alzheimer's specialists agree or refuse to involve their patients. We also need to quantify the impact of requiring imaging studies, extensive questionnaires, cognitive testing, and lumbar punctures on recruitment and retention. With these concerns in mind, an inte...
In the earliest clinical stages of Alzheimer's Disease (AD), when symptoms are mild, clinical... more In the earliest clinical stages of Alzheimer's Disease (AD), when symptoms are mild, clinical diagnosis will still be difficult. AD related molecular mechanisms precede symptoms. Biological markers can serve as early diagnostic indicators, as markers of preclinical pathological change, e.g. underlying mechanisms of action (MoA). Hypothesis based candidates are derived from structural and functional neuroimaging as well as from cerebrospinal fluid (CSF) and plasma. Unbiased exploratory approaches e.g. proteome analysis or rater independent fully automated imaging post-processing methods yield novel candidates. Recent progress in the validation of core feasible imaging and neurochemical biomarkers for functions such as early detection, classification, progression and prediction of AD is summarized. Single core feasible biomarkers can already be used to enrich populations at risk for AD and may be further enhanced using distinct combinations. Some biomarkers are currently in the pr...
The 7th annual meeting of the memory clinics of Germany, Switzerland and Austria in March 2002 in... more The 7th annual meeting of the memory clinics of Germany, Switzerland and Austria in March 2002 in Göttingen, Germany was an optimal opportunity to make an inventory about the state of the art in diagnostic and therapy of dementia and mild cognitive impairment in German-speaking memory clinics. Several problems were discussed including difficulties in 1) diagnosis of patients with aphasia or foreign patients, 2) handling of demented patients without a caregiver, 3) psychological support for patients, who have been diagnosed in a very early stage, 4) misunderstandings between general practitioners, neurologists and psychiatrists in private practice on the one hand and the memory clinics on the other hand, 5) recommendations for prevention of dementia, 6) recommendations concerning dementia and car driving and 7) questions of genetic counselling. The following paper is a summary of the results of a workshop in Göttingen and gives practical recommendations based on the experiences of th...
The CERAD neuropsychological test battery is becoming the standard measure for screening cognitiv... more The CERAD neuropsychological test battery is becoming the standard measure for screening cognitive deficits associated with dementia. The seven subtests of the CERAD battery (Mini-Mental State Examination or MMSE, verbal fluency, Modified Boston Naming Test or MBNT, construction ability, learning of word lists, recall, and recognition), a short test of crystallized intelligence (vocabulary test or WST), and a simple test of visuo-motor tracking (number relation test-G or ZVT-G) were applied to 30 healthy control subjects, 49 depressed patients, and 98 mildly to severely demented patients. All subtests of the CERAD battery separated controls from mildly demented patients. Overall, depressed patients scored between controls and mildly demented patients. Score differences between depressed patients and mildly demented patients were significant for MMSE, learning and recall of the word list, verbal fluency, and MBNT. This paper contains a profile sheet for the CERAD battery developed ac...
Diagnosis upon autopsy of patients suffering from Alzheimer's disease (AD) and other dementin... more Diagnosis upon autopsy of patients suffering from Alzheimer's disease (AD) and other dementing disorders is required to confirm or reject the clinical diagnosis. Autopsy studies are crucial to validate diagnostic criteria as well as to gain new insights in AD epidemiology, genetics, pathophysiology and therapy. The current decrease of autopsy rates leads to a lack of research which is essential to improve diagnosis and therapy of AD. Only the cooperation between physicians in memory-clinics, general practitioners and neuropathologists can prevent this unfortunate development. Brain-Net, the German brain bank, is a unique approach to provide organisational support for such a concerted action.
Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics... more Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD.
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Papers by Harald Hampel