ABSTRACT: Cognitive decline associated with Parkinson disease (PD) is common and highly disabling. Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease.
A total of 45 patients with PD were enrolled in this prospective cohort study and had at least 1 yearly longitudinal follow-up evaluation. CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale (DRS-2). CSF was tested for amyloid β 1-42 (Aβ(1-42)), p-tau(181p), and total tau levels using the Luminex xMAP platform. Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time.
Lower baseline CSF Aβ(1-42) was associated with more rapid cognitive decline. Subjects with CSF Aβ(1-42) levels ≤192 pg/mL declined an average of 5.85 (95% confidence interval 2.11-9.58, p = 0.002) points per year more rapidly on the DRS-2 than subjects above that cutoff, after adjustment for age, disease duration, and baseline cognitive status. CSF total tau and p-tau(181p) levels were not significantly associated with cognitive decline.
Reduced CSF Aβ(1-42) was an independent predictor of cognitive decline in patients with PD. This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD. This biomarker may provide clinically useful prognostic information, particularly if combined with other risk factors for cognitive impairment in PD.
Neurology 09/2010; 75(12):1055-61. · 8.31 Impact Factor
ABSTRACT: Diagnosis of hydatidiform mole by histology and ploidy analysis is limited by overlap of criteria for nonmolar hydropic abortion, complete mole, and partial mole. With early presentation, diagnosis is difficult due to limited tissue and lack of clinical features. Accurate diagnosis of these entities is important for both prognosis and patient management. We assessed a polymerase chain reaction (PCR) assay for polymorphic short tandem repeats (STR) for discrimination between nonmolar hydropic abortion, complete mole, and partial mole based on the genetic composition of molar pregnancies.
Seventeen cases of products of conception (POC) diagnosed by histology and flow cytometry ploidy analysis were studied retrospectively. PCR was performed using maternal and chorionic villus DNA extracted from microdissected, formalin-fixed, paraffin-embedded tissue sections. Allelic patterns for up to eight well-characterized polymorphic STR loci were determined using the GenePrint Fluorescent STR System (Promega Corporation, Madison, WI). The presence of three villus alleles at a single locus was interpreted as partial mole. Detection of only one allele in the villi, different from all maternal allele(s) at the same locus, was interpreted as a complete mole.
This technique identified eight complete moles previously diagnosed as complete mole (3), hydatidiform mole, otherwise unspecified (1), hydropic villi (2), hydropic villi versus partial mole (1), and partial mole (1). The diagnoses of five partial moles by the molecular assay were consistent with the diagnoses by histology and flow cytometry. One nonmolar gestation was identified, which had been diagnosed previously as hydropic villi. In three cases, maternal DNA amplification was insufficient for definitive diagnosis.
Molecular genetic testing of POC from paraffin-embedded tissue accurately distinguishes complete mole, partial mole, and nonmolar hydropic abortion. Identification of triploidy by flow cytometry can confirm a histological impression of partial mole. Histological and ploidy analysis of POC results in underdiagnosis of complete moles.
Molecular Diagnosis 04/1999; 4(1):11-9.
American Journal of Roentgenology 03/1998; 170(2):437-41. · 2.78 Impact Factor
American Journal of Roentgenology 04/1997; 168(3):849-50. · 2.78 Impact Factor