Biomedical subjects

James T Becker

Publications and source records attributed to James T Becker.

30 records · Page 2Linked to original sources

PubMed2003

Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1.

OBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study. DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort. SETTING: Multicenter population study. PATIENTS: We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI. MAIN OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type. RESULTS: The overall prevalence of MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in participants younger than 75 years to 29% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599 participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple cognitive deficits-type was 16%. CONCLUSIONS: Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.

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PubMed2003

Risk factors for mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 2.

OBJECTIVE: To examine the risk factors for mild cognitive impairment (MCI) in a longitudinal population study-the Cardiovascular Health Study Cognition Study. DESIGN: We examined the factors that in the period 1991 through 1994 predicted the development of MCI in all participants of the Cardiovascular Health Study Cognition Study. Further examination was conducted in the Pittsburgh, Pa, cohort (n = 927), where participants with MCI were classified as having either the MCI amnestic-type or the MCI multiple cognitive deficits-type. SETTING: Multicenter population study. PATIENTS: This study includes all participants of the Cardiovascular Health Study Cognition Study (n = 3608) who had a magnetic resonance imaging (MRI) scan of the brain between 1991 and 1994, and detailed neuropsychological, neurological, and medical evaluations to identify the presence of MCI or dementia in the period 1998 to 1999. The mean time between the closest clinical examination to the MRI and the diagnostic evaluation for cognitive disorders was 5.8 years for the Cardiovascular Health Study Cognition Study cohort and 6.0 years for the Pittsburgh cohort. MAIN OUTCOME MEASURES: Risk factors for MCI at the time of the MRI were identified using logistic regression, controlling for age, race, educational level, baseline Modified Mini-Mental State Examination and Digit Symbol Test scores, measurements of depression, MRI findings (atrophy, ventricular volume, white matter lesions, and infarcts), the presence of the apolipoprotein E (APOE) epsilon4 allele, hypertension, diabetes mellitus, and heart disease. RESULTS: Mild cognitive impairment (n = 577) was associated with race (African American), low educational level, low Modified Mini-Mental State Examination and Digit Symbol Test scores, cortical atrophy, MRI-identified infarcts, and measurements of depression. The MCI amnestic-type was associated with MRI-identified infarcts, the presence of the APOE epsilon4 allele, and low Modified Mini-Mental State Examination scores. The MCI multiple cognitive deficits-type was associated with low Modified Mini-Mental State Examination and Digit Symbol Test scores. CONCLUSIONS: The development of MCI is associated with measurements of cognition and depression, racial and constitutional factors, and cerebrovascular disease. Early cognitive deficits seem to be a common denominator for the 2 forms of MCI; the presence of cerebrovascular disease and the APOE epsilon4 allele is associated with the amnestic type of MCI.

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PubMed2003

Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer's disease: correlation with cognitive impairment.

alpha-1-Antichymotrypsin (ACT) is present in neuritic plaques in which it participates in the inflammatory cascade of Alzheimer's disease (AD). Reports of blood ACT levels in AD, and its usefulness as a disease biomarker, have been conflicting. In an effort to clarify this, we measured plasma ACT levels in 516 white subjects including 359 subjects with probable or possible AD, 44 subjects with other late-life dementias, and 113 nondemented people. Subjects with systemic inflammatory diseases or who were taking antiinflammatory medications were excluded. All patients underwent extensive medical and detailed neuropsychological examinations at the time their blood was drawn. We found that plasma ACT levels were elevated in AD patients compared with the control group (p = 0.01) and were associated with severity of AD dementia; there was a negative association with the Mattis Dementia Rating Scale (a global measure of cognition) and a positive association with the Clinical Dementia Rating Scale (a global functional assessment). These relationships remained significant after controlling for demographic and genetic variables. When AD subjects were stratified into subgroups by dementia severity, matched by age, education, and gender, increased serum ACT correlated with Clinical Dementia Rating Scale (p = 0.0041) or Mattis Dementia Rating Scale (p = 0.0031) scores. ACT measurements in cerebrospinal fluid from an additional 34 AD cases and 16 controls showed elevated levels (p = 0.02) in AD. There was a negative correlation (p = 0.037) between cerebrospinal fluid ACT levels and clinical severity as measured by the Mini-Mental State Examination. Our results demonstrate that peripheral ACT levels are elevated in AD, but not in dementias other than AD, and they increase with progression of AD dementia. Although not useful as a diagnostic biomarker, ACT may reflect disease severity and may be helpful as a within subject biomarker in interventions (particularly with antiinflammatory agents) directed at slowing or halting progression of disease.

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PubMed2003

Positron emission tomography imaging of the aging brain.

PET imaging provides a vital means to study the human brain in vivo in aging and early disease states. PET studies using selective markers for brain metabolism and neurotransmitter function have uncovered a wealth of information on healthy and pathologic brain aging, and its relationship to behavior and mood states. Recognition of inherent potential confounds in the use of PET in aging studies is essential to the proper interpretation of these data.

Affect↗

PubMed2003

Psychosocial risk factors of HIV morbidity and mortality: findings from the Multicenter AIDS Cohort Study (MACS).

Despite the use of laboratory markers in estimating HIV prognosis, significant variation in the natural history of HIV-1 infection remains unexplained. Recent studies suggest psychosocial risk factors have important prognostic significance in HIV disease. The objective of the present study was to examine the prognostic influence of age, general intellectual functioning, and emotional distress across the spectrum of HIV disease progression. The study sample was drawn from the Multicenter AIDS Cohort Study (MACS), a 13-year, prospective study of HIV-seropositive men recruited from four study centers across the country. The participants were 1,231 HIV-seropositive MACS participants, followed from baseline (median 8/15/87) to the end of the observation period (12/15/98). HIV disease progression was evaluated with respect to three outcome measures: (1) number of years from baseline testing to the first AIDS defining illness (progression to AIDS), (2) years from baseline to HIV-dementia (progression to dementia), and (3) years from baseline to death (survival). The influence of psychosocial risk factors on outcome measures was evaluated using survival analyses. General intellectual functioning, age, and somatic symptoms of depression, were found to be significant predictors of HIV disease progression and survival. Older age at baseline was associated with a more rapid progression to dementia and death. Lower Shipley IQ estimates were associated with a more rapid disease progression (AIDS and dementia) and shortened survival. Somatic symptoms of depression were associated with shortened survival. In addition, age, IQ, and somatic symptoms of depression, had an additive effect with an increase in the number of risk factors associated with accelerated disease progression and shortened time to death. These findings remained consistent, despite controlling for baseline CD4 and HIV medication use. Psychosocial cofactors are important in understanding HIV disease progression. Methods for estimating HIV prognosis may become more reliable if psychosocial factors are considered. Future research will clarify if psychosocial risk factors reflect central nervous system integrity, brain reserve capacity or mediate morbidity and mortality through social economic status, access to health care and other social correlates.

AIDS Dementia Complex↗

PubMed2003

Patterns of change in the treatment of psychiatric symptoms in patients with probable Alzheimer's disease from 1983 to 2000.

The authors examined the pattern of use of psychiatric medication as prescribed by community physicians in 1,155 patients with probable Alzheimer's disease (AD) referred to the Alzheimer's Disease Research Center of Pittsburgh between April 1983 and July 2000. The use of antidepressants and of sedatives, hypnotics, and anxiolytics (SHA) increased over time, while the use of antipsychotics decreased. The increased use of antidepressants and decreased use of antipsychotics may reflect the growing evidence that newer antidepressants (e.g., selective serotonin reuptake inhibitors) can be used to treat not only mood-related disorders, but also abnormal behavior (e.g., aggression, agitation) and sleep disorders in AD. Although the use of SHA has a proven deleterious effect on patients with AD, their use has increased over the past two decades.

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PubMed2003

Psychiatric symptoms vary with the severity of dementia in probable Alzheimer's disease.

This cross-sectional study examines relationships among the constellation of psychiatric syndromes in Alzheimer's disease (AD) as a function of dementia severity in 1155 patients with probable AD. The frequency of major depression decreased in severe stages, while agitation, aggression, and psychosis were more frequent in late stages. Major depression was associated with anhedonia, sleep disorders, depressed mood, low self-esteem, anxiety, and hopelessness in mild/moderate and severe stages. Agitation was associated with aggression and psychosis in mild/moderate stages, and psychosis was associated with aggression in moderate/severe stages. In addition, there was a constellation of psychiatric symptoms (e.g., anxiety, wandering, irritability, inappropriate behavior, uncooperativeness, emotional lability) associated with agitation, aggression, and psychosis, which varied according to the severity of the dementia, suggesting a progressive deterioration of frontal-temporal limbic structures. Education and race were independently associated with psychosis. However, while education was associated with psychosis in mild/moderate stages, race was associated with psychosis in moderate/severe stages.

Aggression↗

PubMed2002

Recovery of replication-competent HIV type 1-infected circulating monocytes from individuals receiving antiretroviral therapy.

The affect of antiretroviral therapy (ART) on HIV-1 recovery from blood monocytes was determined in purified peripheral blood monocyte-derived macrophage (MDM) cultures from HIV-1-infected subjects with undetectable plasma viremia or active viral replication. Additionally, the association between replication-competent HIV-1-infected MDM and neurocognitive status was examined. Fifty-two individual with previous AIDS-defining illnesses receiving nucleoside analogues with and without protease inhibitors or no ART were followed for up to 1.5 years. Detection of plasma viremia significantly correlated with the occurrence of infected monocytes. Viral replication was detected in less than 10% of the MDM cultures from 23 individuals receiving effective antiretroviral therapy. In contrast, approximately 50% of the MDM cultures from 29 individuals with active viral replication and evidence of decreased immune function, including all individuals with neurocognitive impairment, produced detectable virus indicating that a lack of adequate ART results in increased abundance of replication-competent blood monocytes. Proviral DNA levels were a minimum of 13-fold higher in MDM from subjects with active viral replication. The infrequent detection of viral DNA in cultures from individuals receiving effective ART suggested low levels of circulating monocytes harboring replication-incompetent virus. These studies demonstrate that HIV-infected individuals on ART with breakthrough viremia have significantly higher levels of circulating infected monocytes, the precursors of tissue macrophages.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Research evaluation and prospective diagnosis of dementia with Lewy bodies.

OBJECTIVE: To evaluate the relative merits of recently developed criteria for dementia with Lewy bodies (DLBs) in a longitudinal study of dementia. DESIGN: The diagnosis of DLBs was used in combination with other clinical diagnosis. Patients were classified primarily based on the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) clinical criteria for probable or possible Alzheimer disease, or with other disease process that can cause dementia (eg, Parkinson disease), and secondarily according to the consensus guidelines for DLBs. This "double" clinical diagnosis was implemented to capture different pathological entities. The neuropathological diagnosis of Lewy bodies was made with monoclonal antibodies against alpha-synuclein. SETTING: Multidisciplinary research clinic. RESULTS: Prospective application of the consensus guidelines for DLBs from January 1, 1997, to September 29, 2000, identified 11 patients having the diagnosis of probable DLBs and 35 having possible DLBs. The diagnosis of probable or possible DLBs was associated with probable Alzheimer disease in 34 patients, with possible Alzheimer disease in 5 patients, with Parkinson disease in 2 patients, and with other disease processes in 2 patients. Three patients were diagnosed as having probable DLBs alone. An autopsy was performed in 26 of the cases who were clinically examined during the study period. Cortical Lewy bodies were identified in 13 cases; 4 had had premortem diagnosis of DLBs (sensitivity, 30.7%; specificity, 100%). CONCLUSIONS: The prospective validation of the clinical criteria for DLBs showed poor accuracy in this series. We believe that current criteria for DLBs are useful when DLBs occur in isolation, but have low sensitivity when Lewy bodies coexist with the pathological abnormalities of Alzheimer disease.

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PubMed2002

Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration.

OBJECTIVE: The authors' goal was to compare regional brain volumes in depressed elderly subjects with those of nondepressed elderly subjects by using voxel-based morphometry. METHOD: They used statistical parametric mapping to analyze magnetic resonance imaging scans from 30 depressed patients 59 to 78 years old and 47 nondepressed comparison subjects 55 to 81 years old. RESULTS: Depressed patients had smaller right hippocampal volume than comparison subjects. The volume of the hippocampal-entorhinal cortex was inversely associated with the number of years since the first lifetime episode of depression. CONCLUSIONS: These data provide further evidence of structural brain abnormalities in geriatric depression, particularly in patients with a longer course of illness.

Age Factors↗

PubMedDate not supplied

Evaluation of dementia in the cardiovascular health cognition study.

OBJECTIVE: To describe a methodology to evaluate dementia and frequency of different types of dementia and prevalence of the Cardiovascular Health Study (CHS). METHODS: The CHS is a longitudinal study of cardiovascular disease among community-dwelling individuals over the age of 65. Of the 5,888 participants in the original study, 3,608 had a magnetic resonance imaging (MRI) of the brain in 1991, and formed the cohort for the dementia study. The CHS included yearly measures of cognitive function and, from 1998 to 2000, participants were evaluated for dementia by detailed neurological, and neuropsychological examinations. The possible cases of dementia and mild cognitive impairment (MCI) were adjudicated by a review committee of neurologists and psychiatrists. RESULTS: There were 480 cases of (13.3%) incident dementia in the total sample, 227 (6.3%) prevalent dementia, 577 (16.0%) MCI, and 2,318 (64.4%) normal. The adjudication committee classified 69% of the incident dementia as Alzheimer's disease (AD), 11% as vascular dementia (VaD), 16% as both, and 4% as other types. There was a substantial agreement between pre- and postMRI diagnosis of types of dementia. The frequency of dementia within the CHS cohort which survived to the end of the study in 1998-1999, was 13.5% for white men, 14.5% for white women, 22.2% for black men and 23.4% for black women. CONCLUSION: The CHS has developed a methodology for longitudinal studies of dementia in large cohorts and represents the largest study of dementia including cognitive testing, MRI and genetic markers.

Age Distribution↗

PubMedDate not supplied

Executive functioning, illness course, and relapse/recurrence in continuation and maintenance treatment of late-life depression: is there a relationship?

OBJECTIVE: The authors tested the hypothesis that impaired executive functioning leads to high rates of relapse and recurrence in late-life depression. METHODS: They analyzed data from subjects participating in two independent intervention trials. Study I included 53 elderly depressed patients who participated in an open trial comparing the efficacy of paroxetine and nortriptyline and recurrence prevention over 18 months. Study II focused on 146 elderly depressed patients who received open treatment with paroxetine in a relapse-prevention study over 4 months of continuation treatment. They examined the effect of cognitive functioning, in general, and executive functioning, in particular, on time-to-relapse/recurrence, using baseline and post-treatment measures of neuropsychological functioning. RESULTS: The associations between cognitive measures and both probability of, and time-to-relapse/recurrence were small and statistically nonsignificant. CONCLUSION: Data failed to support the hypothesis that cognitive impairment, in general, or executive dysfunction, in particular, predicts relapse or recurrence of major depression in late life. Authors recommend future testing of the hypothesis with detailed, comprehensive measures over longer periods of observation during maintenance trials.

Age of Onset↗