PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-5 (5)
 

Clipboard (0)
None
Journals
Year of Publication
Document Types
1.  Role of family history for Alzheimer biomarker abnormalities in the adult children study 
Archives of Neurology  2011;68(10):1313-1319.
Objective
To assess whether family history (FH) of Alzheimer’s disease (AD) alone influences AD biomarker abnormalities.
Design
Adult Children Study (ACS).
Setting
Washington University's Knight Alzheimer's Disease Research Center.
Participants
Cognitively normal middle to older age individuals with and without a FH for AD (n=269).
Main Outcome Measures
Clinical and cognitive measures, magnetic resonance imaging (MRI)-based brain volumes, diffusion tensor imaging (DTI)-based white matter microstructure, cerebrospinal fluid (CSF) biomarkers, and molecular imaging of cerebral fibrillar amyloid with positron emission tomography (PET) using the [11C] benzothiazole tracer, Pittsburgh Compound-B (PIB).
Results
A positive FH for AD was associated with an age-related decrease of CSF Aβ42; the ε4 allele of apolipoprotein E (APOE4) did not alter this effect. Age-adjusted CSF Aβ42 was decreased for individuals with APOE4 compared with those without, and the decrease was larger for individuals with a positive FH compared with those without. The variation of CSF tau and PIB mean cortical binding potential (MCBP) increased by age. For individuals younger than 55, an age-related increase in MCBP was associated with APOE4, but not FH. For individuals older than 55, a positive FH and a positive APOE4 implied the fastest age-related increase in MCBP. A positive FH was associated with decreased fractional anisotropy from DTI in the genu and splenium of the corpus callosum.
Conclusion
Independent of APOE4, FH is associated with age-related change of several CSF, PIB and DTI biomarkers in cognitively normal middle to older age individuals, suggesting that non-APOE susceptibility genes for AD influence AD biomarkers.
doi:10.1001/archneurol.2011.208
PMCID: PMC3327304  PMID: 21987546
2.  Comparison of analytical platforms for cerebrospinal fluid measures of Aβ1-42, total tau and p-tau181 for identifying Alzheimer’s disease amyloid plaque pathology 
Archives of neurology  2011;68(9):1137-1144.
OBJECTIVE
Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) are currently being considered for inclusion in revised diagnostic criteria for research and/or clinical purposes to increase the certainty of ante-mortem diagnosis. Establishing biomarker validity requires demonstration that the assays are true markers of underlying disease pathology (e.g., amyloid plaques and/or neurofibrillary tangles) in living individuals.
DESIGN
We compared the performances of the two most commonly used platforms, INNOTEST® ELISA and INNO-BIA AlzBio3 for measurement of CSF amyloid-beta (Aβ) and tau(s), for identifying the presence of amyloid plaques in a research cohort (n=103). Values obtained for CSF Aβ1-42, total tau and phosphorylated tau181 (p-tau181) using the two assay platforms were compared to brain amyloid load as assessed by positron emission tomography using the amyloid imaging agent, Pittsburgh Compound B (PIB).
SUBJECTS
Research volunteers who are cognitively normal or have very mild to moderate AD dementia.
RESULTS
The two assay platforms yielded different (~2–6-fold) absolute values for the various analytes, but relative values were highly correlated. CSF Aβ1-42 correlated inversely, and tau and p-tau181 correlated positively, with the amount of cortical PIB binding, albeit to differing degrees. Both assays yielded similar patterns of CSF biomarker correlations with amyloid load. The ratios of total tau/Aβ1-42 and p-tau181/Aβ1-42 outperformed any single analyte, including Aβ1-2, in discriminating individuals with versus without cortical amyloid.
CONCLUSIONS
The INNOTEST® and INNO-BIA CSF platforms performed equally well in identifying individuals with underlying amyloid plaque pathology. Differences in absolute values, however, point to the need for assay-specific diagnostic cut-point values.
doi:10.1001/archneurol.2011.105
PMCID: PMC3154969  PMID: 21555603
Alzheimer’s disease; amyloid; biomarkers; cerebrospinal fluid; imaging (PET, MRI) in dementias; Pittsburgh Compound B
3.  DONEPEZIL TREATMENT AND CHANGES IN HIPPOCAMPAL STRUCTURE IN VERY MILD ALZHEIMER DISEASE 
Archives of neurology  2010;67(1):99-106.
Objective
We compared longitudinal changes in the hippocampal structure in subjects with very mild dementia of the Alzheimer type (DAT) treated with donepezil, untreated very mild DAT subjects and nondemented controls.
Design
MPRAGE sequences were collected approximately two years apart on two 1.5T Siemens Vision systems, yielding two cohorts. Large-deformation high-dimensional brain mapping was used to compute deformation of hippocampal subfields.
Subjects
Subjects came from two sources: 18 untreated DAT subjects and 26 controls were drawn from a previous longitudinal study; 18 treated DAT subjects were studied prospectively, and 44 controls were drawn from a longitudinal study from the same time period.
Interventions
Patients attending a dementia clinic at Washington University School of Medicine were prescribed Donepezil by their physician.
Results
There was no significant cohort effect at baseline; therefore the two groups of control subjects were combined. The potential confounding effect of cohort/scanner was dealt with by including it as a covariate in statistical tests. There was no significant group effect in the rate-of-change of hippocampal volume or subfields deformation. Further exploration showed that compared with the untreated DAT subjects, the treated DAT subjects did not differ in the rate of change in any of the hippocampal measures. They also did not differ from the controls, while the untreated DAT subjects differed from the controls in the rates-of-change of hippocampal volume, CA1 and subiculum subfield deformations.
Conclusions
Treatment with donepezil did not alter the progression of hippocampal deformation in DAT subjects in this study. Small sample size may have contributed to this outcome.
doi:10.1001/archneurol.2009.292
PMCID: PMC2855123  PMID: 20065136
donepezil; Alzheimer’s disease; hippocampus; magnetic resonance imaging
4.  Education and Reported Onset of Symptoms among Individuals with Alzheimer’s Disease 
Archives of neurology  2008;65(1):108-111.
Objective
To examine whether reported age at onset (AAO) of dementia symptoms among participants with Alzheimer’s disease (AD) is later for those with fewer years of education and, if so, to see if it is attributed to delayed detection of symptoms.
Design
Case series.
Setting
National Alzheimer’s Coordinating Center Minimum Data Set (N=21,880 participants) and Washington University Alzheimer’s Disease Research Center (N=1,449 participants).
Results
Reported AAO of dementia symptoms is slightly earlier for participants with more education. Participants with fewer years of education show greater clinical severity of AD at first assessment.
Conclusion
Symptoms of AD are recognized later among those with less education.
doi:10.1001/archneurol.2007.11
PMCID: PMC2830808  PMID: 18195147
5.  Alzheimer’s and Cognitive Reserve 
Archives of neurology  2008;65(11):1467-1471.
Objective
To evaluate the cognitive reserve hypothesis by examining whether individuals of greater educational attainment have better cognitive function than individuals with less education in the presence of elevated fibrillar brain amyloid.
Design, Setting, and Participants
Uptake of N-methyl-[11C]2-(4′-methylaminophenyl)-6-hydroybenzothiazole, or [11C]PIB for “Pittsburgh Compound-B,” was measured for participants assessed between August 15, 2003 and January 8, 2008 at the Washington University Alzheimer’s Disease Research Center and diagnosed either as nondemented (N=161) or with dementia of the Alzheimer type (N=37). Multiple regression was used to determine whether [11C]PIB uptake interacted with level of educational attainment to predict cognitive function.
Main Outcome Measures
Scores on the Clinical Dementia Rating - Sum of Boxes (CDR-SB), Mini-Mental State Exam (MMSE), and Short Blessed Test (SBT), and individual measures from a psychometric battery.
Results
[11C]PIB uptake interacted with years of education in predicting scores on the CDR-SB (p=.003), the MMSE (p<.001), the SBT (p=.03) and a measure of verbal abstract reasoning and conceptualization (p=.02), such that performance on these measures increased with increasing education for participants with elevated PIB uptake. Education was unrelated to global cognitive functioning scores among those with lower PIB uptake.
Conclusions
These results support the hypothesis that cognitive reserve influences the association between Alzheimer disease pathology and cognition.
doi:10.1001/archneur.65.11.1467
PMCID: PMC2752218  PMID: 19001165

Results 1-5 (5)