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1.  Dual Immunofluorescence Study of Citrullinated Proteins in Alzheimer Diseased Frontal Cortex 
Neuroscience letters  2013;545:107-111.
Deimination is a post-translational modification of proteins in which selected arginine amino acids are enzymatically converted to citrullines. Using dual-color immunofluorescence, the present study is the first to examine the frontal cortex of patients with Alzheimer's disease (AD) versus age-matched controls with an established monoclonal antibody (F95) against peptidyl-citrulline moieties. In AD specimens, a number of new findings were discovered, including evidence for deiminated proteins in extracellular plaques, the walls of large blood vessels, the nuclei of selective neurons immunoreactive for phosphorylated tau and numerous reactive astrocytes concentrated around extracellular plaques, ventricular surfaces and at the interface between the gray and white matter of the cortex. Although the identities of these citrullinated proteins remain largely unknown, the present study adds to the growing number of locations in which deiminated proteins may be found in the brains of patients with AD.
PMCID: PMC3731154  PMID: 23648390
amyloid beta; citrulline; deimination; glial fibrillary acidic protein; peptidyl arginine deiminase; tau
2.  Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis 
Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination.
Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intraarticular glucocorticoid injection, and eight healthy volunteers. Synovial inflammation was assessed with double-blind semiquantitative analysis of lining thickness, cell infiltration, and vascularity by using a 4-point scale. Expression of citrullinated proteins (CPs) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically with double-blind semiquantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB), mononuclear cells (MCs), and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed with immunohistochemistry for expression of CP as well as PAD2 and PAD4 enzymes.
The presence of synovial CP was almost exclusive in RA compared with healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination, as demonstrated by the decrease in the level of citrullination and PAD expression after incubation of SFMC and synovial explants with dexamethasone.
Synovial citrullination and PAD expression are dependent on local inflammation and targeted by glucocorticoids.
PMCID: PMC3392813  PMID: 22284820
3.  Clinical Interview Assessment of Financial Capacity in Older Adults with Mild Cognitive Impairment and Alzheimer’s Disease 
To investigate financial capacity in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using a clinician interview approach.
Tertiary care medical center.
Healthy older adults (N=75), patients with amnestic MCI (N=58), mild AD (N=97), and moderate AD (N=31).
The investigators and five study physicians developed a conceptually based, semi-structured clinical interview for evaluating seven core financial domains and overall financial capacity (Semi-Structured Clinical Interview for Financial Capacity; SCIFC). For each participant, a physician made capacity judgments (capable, marginally capable, or incapable) for each financial domain and for overall capacity.
Study physicians made a total of over 11,000 capacity judgments across the study sample (N=261). Very good inter-rater agreement was obtained for the SCIFC judgments. Increasing proportions of marginal and incapable judgment ratings were associated with increasing disease severity across the four study groups. For overall financial capacity, 95 percent of physician judgments for older controls were rated as capable, as compared to only 82% for patients with MCI, 26% for patients with mild AD, and 4% for patients with moderate AD.
Financial capacity in cognitively impaired older adults can be reliably evaluated by physicians using a relatively brief, semi-structured clinical interview. Financial capacity shows mild impairment in MCI, emerging global impairment in mild AD, and advanced global impairment in moderate AD. MCI patients and their families should proactively engage in financial and legal planning given these patients’ risk of developing AD and accelerated loss of financial abilities.
PMCID: PMC2714907  PMID: 19453308
financial capacity; competency; clinical assessment; mild cognitive impairment; Alzheimer’s disease
4.  The Contribution of Executive Control on Verbal-Learning Impairment in Patients with Parkinson's Disease with Dementia and Alzheimer's Disease 
Deficits in learning, memory, and executive functions are common cognitive sequelae of Parkinson's disease with dementia (PDD) and Alzheimer's disease (AD); however, the pattern of deficits within these populations is distinct. Hierarchical regression was used to investigate the contribution of two measures with executive function properties (Verbal Fluency and CLOX) on list-learning performance (CVLT-II total words learned) in a sample of 25 PDD patients and 25 matched AD patients. Executive measures were predictive of list learning in the PDD group after the contribution of overall cognition and contextual verbal learning was accounted for, whereas in the AD group the addition of executive measures did not add to prediction of variance in CVLT-II learning. These findings suggest that deficits in executive functions play a vital role in learning impairments in patients with PDD; however, for AD patients, learning difficulties appear relatively independent of executive dysfunction.
PMCID: PMC2765349  PMID: 19587066
Parkinson's disease with dementia; Alzheimer's disease; Executive function; List learning; Neuropsychologic tests; Comparative studies
5.  Medical Decision-Making Capacity in Cognitively Impaired Parkinson's Disease Patients Without Dementia 
Little is currently known about the higher order functional skills of patients with Parkinson disease and cognitive impairment. Medical decision-making capacity (MDC) was assessed in patients with Parkinson's disease (PD) with cognitive impairment and dementia. Participants were 16 patients with PD and cognitive impairment without dementia (PD-CIND), 16 patients with PD dementia (PDD), and 22 healthy older adults. All participants were administered the Capacity to Consent to Treatment Instrument (CCTI), a standardized capacity instrument assessing MDC under five different consent standards. Parametric and non-parametric statistical analyses were utilized to examine capacity performance on the consent standards. In addition, capacity outcomes (capable, marginally capable, or incapable outcomes) on the standards were identified for the two patient groups. Relative to controls, PD-CIND patients demonstrated significant impairment on the understanding treatment consent standard, clinically the most stringent CCTI standard. Relative to controls and PD-CIND patients, patients with PDD patients were impaired on the three clinical standards of understanding, reasoning, and appreciation. The findings suggest that impairment in decisional capacity is already present in cognitively impaired PD patients without dementia, and increases as these patients develop dementia. Clinicians and researchers should carefully assess decisional capacity in all PD patients with cognitive impairment.
PMCID: PMC2579319  PMID: 18759361
consent capacity; medical decision-making; cognitive impairment without dementia; functional change; Parkinson's disease

Results 1-5 (5)