Biomedical subjects

R Au

Publications and source records attributed to R Au.

10 recordsLinked to original sources

PubMed2004

Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study.

BACKGROUND: Mid-life stroke risk factors have been related to late-life cognitive impairment. This association may result not only from clinical strokes but also from subclinical brain injury, such as a global atrophy demonstrable on quantitative brain MRI. METHODS: The authors evaluated the community-based cohort of Framingham Offspring Study participants. A total of 1,841 subjects (mean age, 62 years; 857 men, 984 women) who underwent quantitative MRI and cognitive testing between 1999 and 2001 and were free of clinical stroke and dementia constituted our study sample. The authors used age- and sex-adjusted linear regression models to relate previous (1991 to 1995) and recent (1998 to 2001) Framingham Stroke Risk Profile (FSRP) scores to the total cerebral brain volume ratio (TCBVr) on follow-up MRI, and further to relate the TCBVr with education-adjusted scores on neuropsychological tests administered at the time of imaging. RESULTS: There was an inverse association between FSRP scores and TCBVr. The TCBVr also showed a significant positive association with performance on tests of attention (Trails A), executive function (Trails B), and visuospatial function (visual reproduction, Hooper visual organization), but not with performance on tests of verbal memory or naming. CONCLUSIONS: The Framingham Stroke Risk Profile may identify subjects with smaller brains and poorer cognitive function among stroke- and dementia-free subjects, reinforcing the importance of managing stroke risk factors.

Adult↗

PubMed2000

The preclinical phase of alzheimer disease: A 22-year prospective study of the Framingham Cohort.

OBJECTIVES: To relate performance on tests of cognitive ability to the subsequent development of probable Alzheimer disease (pAD) and to identify the pattern of earliest changes in cognitive functioning associated with a diagnosis of pAD. DESIGN: From May 1975 to November 1979, a screening neuropsychological battery was administered to Framingham Study participants. They were followed up prospectively for 22 years and examined at least every 2 years for the development of pAD. SETTING: A community-based center for epidemiological research. PARTICIPANTS: Subjects were 1076 participants of the Framingham Study aged 65 to 94 years who were free of dementia and stroke at baseline (initial) neuropsychological testing. MAIN OUTCOME MEASURE: Presence or absence of pAD during a 22-year surveillance period was related to test performance at initial neuropsychological testing. RESULTS: Lower scores for measures of new learning, recall, retention, and abstract reasoning obtained during a dementia-free period were associated with the development of pAD. Lower scores for measures of abstract reasoning and retention predicted pAD after a dementia-free period of 10 years. CONCLUSIONS: The "preclinical phase" of detectable lowering of cognitive functioning precedes the appearance of pAD by many years. Measures of retention of information and abstract reasoning are among the strongest predictors of pAD when the interval between initial assessment and the development of pAD is long. Arch Neurol. 2000.

Aged↗

PubMed2000

Docetaxel (Taxotere) in combination with anthracyclines in the treatment of breast cancer.

Considering the single-agent activity of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and doxorubicin in breast cancer and their potential non-cross-resistance, several docetaxel/anthracycline-based combination chemotherapies were developed in phase I and II programs for metastatic breast cancer patients. The rationale for these combinations was also reinforced by the fact that docetaxel showed significant activity in phase III trials in patients previously exposed or having failed anthracycline chemotherapy. In a pivotal randomized phase III study of doxorubicin plus docetaxel versus doxorubicin plus cyclophosphamide as first-line chemotherapy for 429 patients with metastatic breast cancer, doxorubicin/docetaxel emerged as the more effective regimen. Despite a lower-dose intensity of doxorubicin, patients receiving doxorubicin/docetaxel experienced a higher response rate as well as a significantly longer time to progression and time to treatment failure. This difference was seen even in patients with poor-prognosis disease. Febrile neutropenia was more common in doxorubicin/docetaxel-treated patients. However, there were no septic deaths among 213 patients receiving doxorubicin/ docetaxel. Extrahematologic toxicity appeared mild for both regimens and the combination docetaxel/doxorubicin did not increase the cardiac toxicity expected for an anthracycline-containing regimen. Docetaxel plus doxorubicin is the first regimen, involving a newly developed agent, proven superior to a standard anthracycline-containing combination in metastatic breast cancer and its potential is now being investigated in the adjuvant setting.

Antibiotics, Antineoplastic↗

PubMed1999

Verb naming in normal aging.

Few studies have examined verb naming in normal aging, although decline in the ability to name nouns has been well documented. In this study, we examined longitudinal performance on the Action Naming Test (ANT), a confrontation naming test for verbs. The purpose of this study was to confirm the verb naming deficit associated with aging, which was previously seen only in cross-sectional studies, and to provide additional normative data on verb naming ability that may prove useful to studies on verb naming in populations with brain dysfunction. Sixty-six healthy men and women aged 30 to 79 were each tested with the ANT 3 times over a 7-year span. ANT performance showed a significant decline over time for all participants except the youngest group. Longitudinal methodology supports the conclusion that this finding of a decline in verb naming ability arises from true age-related changes and not from cohort differences.

Adult↗

PubMed1999

Docetaxel and anthracycline polychemotherapy in the treatment of breast cancer.

Given the single-agent activity of docetaxel and doxorubicin in metastatic breast cancer and their potential non-cross-resistance, several phase I/II pilot studies of either docetaxel/doxorubicin (TA) or TA plus cyclophosphamide (TAC) were conducted. The results of these studies show that the main toxicity is related to neutropenia and its consequences, although documented infections are rarely reported. Other toxicities are mild, while docetaxel-specific toxicities (fluid retention, nail changes, etc) are seldom seen. No significant cardiotoxicity, even when patients are exposed to a cumulative doxorubicin dose greater than 360 mg/m2, has been observed. In terms of efficacy, response rates in the range of 70% to 80% were noted in all studies, even for patients with visceral metastases. Preliminary data suggest that the combination of docetaxel with epirubicin is also feasible, with manageable toxicities and significant activity. Several phase III randomized trials using TA or TAC are presently being performed in first-line metastatic breast cancer and, most importantly, in the adjuvant setting to assess whether TA-based combinations will change the natural history of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Lifetime risk of dementia and Alzheimer's disease. The impact of mortality on risk estimates in the Framingham Study.

We estimated the remaining lifetime risks of developing Alzheimer's disease (AD) and dementia from all causes, based on data from longitudinal population studies. The risk of developing AD during one's lifetime depends on both disease incidence and life expectancy. Conventional estimates of cumulative incidence overestimate the risk when there is a substantial probability of mortality due to competing causes. A total of 2,611 cognitively intact subjects (1,061 men, 1,550 women; mean age, 66 +/- 7 years) were prospectively evaluated for the development of AD or other dementia. A modified survival analysis was used to estimate both cumulative incidence and the sex-specific remaining lifetime risk estimates for quinquennial age groups above age 65 years. Over a 20-year follow-up period, 198 subjects developed dementia (120 with AD). The remaining lifetime risk of AD or other dementia depended on sex, being higher in women, but varied little with age between 65 and 80 years. In a 65-year-old man, the remaining lifetime risk of AD was 6.3% (95% CI, 3.9 to 8.7) and the remaining lifetime risk of developing any dementing illness was 10.9% (95% CI, 8.0 to 13.8); corresponding risks for a 65-year-old woman were 12% (95% CI, 9.2 to 14.8) and 19% (95% CI, 17.2 to 22.5). The cumulative incidence between age 65 and 100 years was much higher: for AD, 25.5% in men and 28.1% in women; for dementia, 32.8% in men and 45% in women. The actual remaining lifetime risk of AD or dementia varies with age, sex, and life expectancy and is lower than the hypothetical risk estimated by a cumulative incidence in the same population.

Aged↗

PubMed1996

On the nature of naming errors in aging and dementia: a study of semantic relatedness.

This study investigated the nature of naming errors produced on the Boston Naming Test by patients with mild and moderate Alzheimer's disease (AD) and elderly and young controls, using a newly devised scoring system. This new approach involved ratings of error responses on a scale of semantic relatedness to the target name. Error responses of both mild and moderate AD subjects were no less semantically related to target names than were responses of age- and education-matched controls. We conclude that some available evidence of semantic loss in AD may be an artifact of the methodology chosen for evaluating naming errors.

Adult↗

PubMed1996

Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study.

Apolipoprotein E type 4 allele (apoE epsilon4) is associated with Alzheimer's disease (AD) in the late-onset familial form and in sporadic cases, but the age-associated risk in a randomly sampled elderly population is not established. We examined the association of apoE epsilon4 with AD and other dementias (mainly multi-infarct or dementia following stroke) in 1,030 persons aged 71 to 100 years in the population-based Framingham Study cohort. Kaplan-Meier survival analysis revealed that 55% of the apoE epsilon4/epsilon4 homozygotes developed AD by age 80, whereas 27% of apoE epsilon3/epsilon4 heterozygotes developed AD by age 85, and 9% of those without a 4 allele developed AD by age 85 years. In comparison with persons without a 4 allele, the risk ration for AD was 3.7 (95% CI = 1.9 to 7.5) for apoE epsilon3/epsilon4 heterozygotes and 30.1 (95% CI = 10.7 to 84.4) for apoE epsilon4 homozygotes. ApoE epsilon2 (2/2, 2/3, or 2/4 genotypes) was associated with an absence of AD. One-half (n=21) of the 43 AD patients were either homozygous or heterozygous for apoE epsilon4. We found evidence for an association of apoE epsilon4 with other dementia, primarily multi-infarct dementia and stroke. The risk ratio was 2.3 (95% CI = 0.9 to 6.1) for non-AD dementias among persons with apoE epsilon3/epsilon4. Although the apoE epsilon4 allele is a potent risk factor for AD and may be associated with other forms of dementia, most apoE epsilon4 carriers do not develop dementia, and about one-half of AD is not apoE epsilon4 associated. The low positive predictive value of this marker (0.10) suggest that use of apoE genotyping as a screening test for AD is not supported.

Adult↗

PubMed1995

The effect of education on the incidence of dementia and Alzheimer's disease in the Framingham Study.

OBJECTIVE: To evaluate whether low educational attainment is a risk factor for the incidence of dementia and Alzheimer's disease (AD) in the Framingham Study and to determine whether age at onset of dementia is earlier in persons with low educational levels. DESIGN: A community-based cohort was studied longitudinally for the development of dementia. Diagnosis was made according to strict criteria by two neurologists and a neuropsychologist. Subtype of dementia and year at onset were determined. Incidence rates were compared in three education groups: < grade school, < high school, and > or = high school. PARTICIPANTS: A total of 3,330 men and women aged 55 to 88 years. RESULTS: During 17 years of follow-up, 258 incident cases of dementia, including 149 AD cases, were identified. Unadjusted incidence rates were significantly elevated (p < 0.05) for dementia and non-AD dementia among the least educated. The age-adjusted relative risk for subjects with a grade school education or less compared with those who earned a high school diploma was 1.31 (95% confidence interval [CI], 0.90 to 1.90) for dementia generally, 1.04 (95% CI, 0.62 to 1.74) for AD, and 1.75 (95% CI, 1.03 to 2.98) for non-AD dementia. Age at onset of dementia did not vary by educational attainment. CONCLUSIONS: After age adjustment, low educational attainment was not a significant risk factor for the incidence of dementia generally or of AD. Low educational attainment was associated with increased risk of non-AD dementia, perhaps because of deleterious smoking habits and other risk factors for stroke in the least-educated individuals. Adequately adjusting for age and examining subtypes of dementia are important in assessing the influence of education on dementia incidence.

Age of Onset↗

PubMed1992

Speech monitoring skills in Alzheimer's disease, Parkinson's disease, and normal aging.

We examined the abilities of 15 patients with dementia of the Alzheimer type (DAT), 22 patients with Parkinson's Disease (PD), and 141 healthy subjects (ranging in age from 30 to 79 years) to detect and correct their own speech errors. Each subject was shown the Cookie Theft picture of the BDAE (Goodglass & Kaplan, 1972. The assessment of aphasia and related disorders. Philadelphia: Lea & Febiger.) and instructed to tell the examiner the "...story of what's happening in the picture." Self-monitoring performance was assessed by tabulating the number of uncorrected errors as well as repaired errors. We divided repairs into two types based on the psycholinguistics literature (van Wijk & Kempen, 1987. Cognitive Psychology, 19, 403-440). Speech corrections were judged to be lemma repairs when the reparandum was a single word, and reformulation repairs when a new syntactic constituent was added to the reparandum. Patients with DAT corrected only 24% of their total errors and patients with PD only 25%. Healthy subjects, by contrast, corrected from 72 to 92% of their total errors. Patients with DAT tended to rely on reformulation repairs while patients with PD used both repair types about equally often. While healthy elderly Ss (in the 70s group) utilized lemma repairs more often than the reformulation strategy, all other healthy Ss used both strategies about equally often. Across all groups naming performance correlated negatively with numbers of undetected errors. Results point to a previously unrecognized communication disorder associated with PD and DAT and manifested by an impairment in the ability to correct output errors. This impairment may be related to attentional and frontal dysfunction in the two patient groups.

Adult↗