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Biomedical subjects

K A Jellinger

Publications and source records attributed to K A Jellinger.

At least 37 records · Page 2Linked to original sources
PubMed2002

Impact of coexistent Alzheimer pathology on the natural history of Parkinson's disease.

OBJECTIVE: To assess the impact of coexisting Alzheimer (AD) pathology on the natural history of Parkinson's disease (PD). BACKGROUND: AD changes are frequently present in brains of demented PD patients. Assessing the relative contribution of AD pathology to the natural history of PD is difficult and the impact of both AD and cortical Lewy body (LB) pathologies on cognitive dysfunction is still under discussion. From clinical experience, dementia in PD patients, mainly related to AD pathology, is associated with a poor outcome, but the impact of AD pathology on the natural history of PD has not been studied systematically. MATERIAL AND METHODS: In 200 consecutive autopsy cases of PD (sex (m/f) ratio 1:1.1), age at death 58-98 (mean 77.0 +/- 9.5) years, from a specialized Austrian brain bank, retrospectively assessed major initial clinical symptoms (tremor, akinesia), moderate/severe dementia, and duration of illness were correlated with associated AD pathologies using CERAD, Braak and NIA-Reagan criteria. Mann-Whitney U-test, Cox-regression were used for statistical analysis. RESULTS: While gender had no influence on the clinical motor symptoms and outcome, tremor dominant type had a significantly better outcome than akinetic forms (p = 0.022), even after adjustment with age at onset and associated AD pathology (CERAD and Braak criteria). Patients with late onset showed significantly shorter duration of illness irrespective of dementia. Moderate to severe dementia, reported in 33% of the sample, was significantly correlated with AD pathology (all 3 criteria) that showed significantly negative correlation with survival: between CERAD 0-A vs. B and C there was a significant difference of odd ratios (p < 0.001), as was between Braak stages 0-2, 3-4.5, and 5, but not between Braak stages 3-4 and 5. CONCLUSIONS: The present data confirm previous studies suggesting better outcome of tremor-dominant than akinetic-rigid type of PD, significantly worse outcome in PD with late onset and dementia that is significantly correlated with coexistent neuritic Alzheimer pathology, particularly when using the CERAD and NIA-R criteria for the diagnosis of AD. Further studies are needed to elucidate the relative impact of cortical LB and AD pathologies on the natural history of PD.

Age of Onset↗
PubMed2002

Alzheimer disease and cerebrovascular pathology: an update.

Recent epidemiological and clinico-pathologic data suggest overlaps between Alzheimer disease (AD) and cerebrovascular lesions that may magnify the effect of mild AD pathology and promote progression of cognitive decline or even may precede neuronal damage and dementia. Vascular pathology in the aging brain and in AD includes: 1. cerebral amyloid angiopathy (CAA) with an incidence of 82-98% often associated with ApoE epsilon 2 and causing a) cerebral mass hemorrhages (around 70%, mainly in the frontal and parietal lobes), b) multiple or recurrent microhemorrhages (15%), and c) ischemic (micro-)infarcts or lacunes (around 20%). The frequency of these lesions increases with the severity of CAA and shows no correlation with that of senile amyloid plaques. CAA, significantly more frequent in patients with cerebral hemorrhages or infarcts than in aged controls, is an important risk factor for cerebrovascular lesions in AD. 2. Microvascular changes with decreased density and structural abnormalities causing regional metabolic and blood-brain barrier dysfunctions with ensuing neuronal damage. In large autopsy series of demented aged subjects, around 80% show Alzheimer type pathology, 20-40% with additional, often minor vascular lesions, 7-10% "pure" vascular dementia, and 3-5% "mixed" dementia (combination of AD and vascular encephalopathy). AD cases with additional minor cerebrovascular lesions have significantly more frequent histories of hypertension or infarcts than "pure" AD patients. Vascular lesions in AD include cortical microinfarcts, subcortical lacunes, white matter lesions / leukoencephalopathy, small hemorrhages and corticosubcortical infarcts, while in mixed type dementia multiple larger or hemispheral infarcts are more frequent. Small infarcts in AD patients have no essential impact on global cognitive decline which mainly depends on the severity of Alzheimer pathology, but in early stage of AD they may influence and promote the development of dementia. Recent studies showed lower density of plaques and tangles in brains with cerebrovascular lesions, and similar severity of dementia was related to fewer AD lesions in brains with than in those without small vascular lesions. Further studies will help to elucidate the risk factors and impact of cerebrovascular lesions on the development and progression of dementia in AD.

Alzheimer Disease↗
PubMed2001

Traumatic brain injury as a risk factor for Alzheimer disease. Comparison of two retrospective autopsy cohorts with evaluation of ApoE genotype.

BACKGROUND AND PURPOSE: The impact of traumatic brain injury (TBI) on the pathogenesis of Alzheimer disease (AD) is still controversial. The aim of our retrospective autopsy study was to assess the impact of TBE and ApoE allele frequency on the development of AD. MATERIAL AND METHODS: We examined 1. the incidence of AD pathology (Braak stageing, CERAD, NIA-Reagan Institute criteria) in 58 consecutive patients (mean age +/- SD 77.0 +/- 6.8 years) with residual closed TBI lesions, and 2. the frequency of TBI residuals in 57 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material. RESULTS: 1. TBE series: 12.1 % showed definite and 10.3% probable AD (mean age 77.6 and 75.2 years), only 2/13 with ApoEepsilon3/4. From 45 (77.6%) non-AD cases (mean age 78.2 years), 3 had ApoEepsilon3/4. The prevalence of 22.4% AD in this small autopsy cohort was significantly higher than 3.3% in a recent large clinical series and 14% in the general population over age 70. 2. In the AD cohort with ApoEepsilon4 allele frequency of 30% similar to other AD series, residuals of closed TBI were seen in 4 brains (7%) (mean age +/- SD 78.2 +/- 6.4), all lacking the ApoEepsilon4 allele. TBI incidence was slightly lower than 8.5% in the clinical MIRAGE study. CONCLUSIONS: The results of this first retrospective autopsy study of TBI, ApoEepsilon allele frequency, and AD confirm clinical studies suggesting severe TBI to be a risk factor for the development AD higher in subjects lacking ApoEepsilon4 alleles. Further studies in larger autopsy series are needed to elucidate the relationship between TBI, genetic predisposition, and AD.

Aged↗
PubMed2001

Ex vivo lumbar and post mortem ventricular cerebrospinal fluid substance P-immunoreactivity in Alzheimer's disease patients.

The concentration of substance P-immunoreactivity (SPIR) in ex vivo lumbar cerebrospinal fluid (CSF) of patients with probable Alzheimer's disease (AD), non-Alzheimer dementias, neurological patients without dementia and control subjects was determined using a sensitive and specific competitive enzyme-immunoassay. There were no significant differences between AD patients and the other groups, but patients with late onset AD (>65 years) showed significantly higher levels of SPIR than patients with early onset (<65 years) and controls. In post mortem ventricular fluid, SPIR levels of all groups were lower compared with the lumbar compartment, but without significant group differences. It is concluded that CSF SPIR may not serve as a diagnostic marker for AD, but possibly could reflect immunological or neuroprotective processes modulated by substance P in late onset AD patients.

Age of Onset↗
PubMed2001

Apoptosis signals in sporadic amyotrophic lateral sclerosis: an immunocytochemical study.

Sporadic amyotrophic lateral sclerosis (sALS) is a neurodegenerative disorder of unknown cause characterized by selective loss of both upper and lower motor neurons. Whether neuronal death in sALS is due to apoptosis has so far not been clarified. In this study, the expression and distribution patterns of pro- and anti-apoptotic bcl-2 family members as well as the executioner caspase-3 were investigated in post-mortem CNS tissue of eight sALS patients and seven age-matched controls. Sparse motor neurons were immunoreactive for bcl-2, bax, bak, and CM1 on serial sections through the spinal cord and motor cortex of individual sALS patients and controls. However, there was no obvious difference in the numbers of immunoreactive (IR) neurons between the two groups. The study did not find evidence for apoptosis as a major mechanism of motor neuronal cell death in sALS.

Aged↗
PubMed2001

Cognitive relapse after discontinuation of drug therapy in Alzheimer's disease: cholinesterase inhibitors versus nootropics.

In a cross-sectional study of outpatients diagnosed with dementia of the Alzheimer type who had been treated with a broad variety of drugs supposed to improve cognition or to delay cognitive decline, we have investigated the effects of abruptly discontinuing therapy on cognition. Termination of therapy with any cholinesterase inhibitor was associated with a cognitive decline during the following 6-7 weeks which was significantly more pronounced than that experienced by patients who had received nootropic drugs or calcium channel blockers (3.41 vs. 1.17 points on the ADAS-Cog scale; -1.14 vs. -0.06 points on the MMSE scale). This effect was not modified by gender, apolipoprotein E genotype, or the extent of ventricular enlargement on CT scans. Its magnitude was comparable to the cognitive response observed in published clinical trials when cholinesterase therapy commenced, and also with the data obtained during a 6-week placebo washout phase.

Acetylcholinesterase↗
PubMed2001

Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer's disease patients.

Immunoreactivities of total apolipoprotein E (ApoE-IR), amyloid beta peptide(1-42) (Abeta42-IR), interleukin-6 (IL-6-IR), substance P (SPIR) and total tau protein (TTIR) were measured in lumbar cerebrospinal fluid samples of patients with Alzheimer's disease (AD), non-Alzheimer's dementias (NAD), neurological disorders without cognitive impairment (OND) and controls without central nervous system disease using sensitive and specific enzyme immunoassay methods. TTIR was highly significantly increased (P < 0,001) and Abeta42-IR was significantly decreased (P < 0,001 vs. OND/CO, P < 0,03 vs. NAD) in the AD cohort compared with the other diagnostic groups. Significant increases in AD were also found for ApoE-IR (P < 0,001) and IL-6 (P < 0,03), but there was a considerable overlap between groups. In the total AD cohort, SPIR was not significantly changed, but AD patients with late disease onset (>65 years) showed significantly higher values than both early onset patients (<65 years) and controls (P < 0,05). Discriminant function analysis showed that Abeta42-IR (cut-off value 375pg/ml) and TTIR (cut-off value 440 pg/ml) levels contributed most to the group classification of patients. At 85% sensitivity for AD and 100% specificity for controls, the combined evaluation of Abeta42-IR and TTIR in this cross-sectional study resulted in a graph separating AD from non-AD patients with increased specificity of 91% and 75% for AD versus OND and NAD, respectively.

Aged↗
PubMed2001

Intra vitam lumbar and post mortem ventricular cerebrospinal fluid immunoreactive interleukin-6 in Alzheimer's disease patients.

OBJECTIVES: In view of contradictory findings in previous studies, to examine the diagnostic value of interleukin-6 measurements in cerebrospinal fluid (CSF) of Alzheimer's disease patients. MATERIAL AND METHODS: Interleukin-6-immunoreactivity (IL-6-IR) was measured in 169 intra vitam lumbar and 21 post mortem ventricular CSF samples of patients with probable and neuropathologically confirmed Alzheimer's disease (AD), non-AD dementias (NAD), neurological disorders without cognitive impairment (OND) and controls (CON) using a specific sandwich enzyme immunoassay. RESULTS: Intra vitam lumbar samples had significantly elevated (P < 0.03) IL-6-IR not only in the AD, but also in the NAD and OND group compared with controls. AD patients with late onset (> 65 years) had slightly (P > 0.05) higher values than patients with early onset (< 65 years). In post mortem ventricular fluid, differences among groups did not reach significance (P > 0.05). CONCLUSION: We conclude that elevations of CSF IL-6-IR can not serve as a diagnostic marker of the disease, but, hypothetically, could reflect presence or activity of IL-6 mediated immunological phenomena in single AD patients.

Aged↗
PubMed2001

Effects of closed traumatic brain injury and genetic factors on the development of Alzheimer's disease.

In order to assess the impact of traumatic brain injury (TBI) and Apolipoprotein E (ApoE) allele frequency on the development of Alzheimer's disease (AD), we examined: (i) the incidence of AD pathology in 55 consecutive autopsy cases (mean age +/- SD 77.6 +/- 7.3 years) with residual closed TBI lesions and (ii) the frequency of TBI residuals in 53 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material. The results were as follows: (i) In the TBI series, 12.7% showed Consortium to Establish a Registry for Alzheimer's disease (CERAD) definite and 9.1% probable AD, only one with ApoEepsilon4. From the remaining 43 non-AD cases, three had ApoEepsilon4. The prevalence of 21.8% AD in this small autopsy cohort was significantly higher than 3.3% in a recent large clinical series and 14% in the general population over the age of 70. (ii) In the AD cohort with ApoEepsilon4 allele frequency of 30% similar to other AD series, residuals of TBI were seen in 4 brains (7.5%), all lacking the ApoEepsilon4 allele. TBI incidence was slightly higher than 8.5% in the clinical MIRAGE study. The results of this first retrospective autopsy study of TBI, ApoE allele frequency, and AD confirms clinical studies suggesting severe TBI to be a risk factor for the development of AD particularly in subjects lacking ApoEepsilon4.

Aged↗