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J Saxton

Publications and source records attributed to J Saxton.

At least 19 recordsLinked to original sources
PubMed2005

Functional neuroimaging indicators of successful executive control in the oldest old.

Attentional control, motor planning abilities, and executive cognitive functions (ECF) rapidly decline with age. In particular, older adults experience difficulty in manipulating selected motor responses in the presence of conflicting or distracting information. To examine age-related changes in the neural substrates of the attentional and motor planning components of ECF, we assessed the patterns of brain activation in 8 cognitively normal older adults (mean age 81.5) and 20 young individuals (mean age 23.0) while they responded to low and high loads of attentional demands of the Preparing to Overcome Prepotency (POP) task. In the POP task, the selection of one out of two possible motor responses in the presence of increasing attentional task loads determines the accuracy of the performance. Older individuals were slower than young adults (P < 0.001) but achieved a strikingly high accuracy similar to the young group (P = 0.2), regardless of the task load. Both groups showed a load-related fMRI signal increase in the anterior cingulate cortex (ACC), posterior parietal cortex (PPC: Brodmann areas 7 and 40), and dorsolateral prefrontal cortex (dLPFC: Brodmann areas 9, 45, and 46) bilaterally. Compared to young individuals, older adults had lower activation in dLPFC (Brodmann areas 9, 45, and 46: P = 0.007, P = 0.043, and P = 0.040) and Brodmann area 7, P = 0.002. Activation in Brodmann areas 40 and ACC was similar in the two groups (P > 0.05). Among older adults, the most successful performers were those who responded to increasing task loads with greater activation in PPC (Brodmann area 40), despite lower dLPFC activation. Older adults who are able to perform executive control tasks as well as young adults, also seem to implement speed-accuracy trade-off strategies which may rely on increased parietal activation.

Adolescent↗
PubMed2004

Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset.

OBJECTIVE: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset. METHODS: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years). RESULTS: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later. CONCLUSIONS: Cognitive changes can be detected well before onset of Alzheimer disease.

Age of Onset↗
PubMed2003

A critique of a UK standardized test of finger rewarming after cold provocation in the diagnosis and staging of hand-arm vibration syndrome.

BACKGROUND: Accurate diagnosis and staging of hand-arm vibration syndrome (HAVS) is important in health surveillance of vibration-exposed workers and the substantial number of related medico-legal cases. The measurement of the rewarming rate of fingers after cold provocation to the hands (CPT) has been suggested as a useful test in diagnosing HAVS. AIM: To investigate the diagnostic value of a standardized version of the CPT test using a 15 degrees C cold challenge for 5 min applied in the recent compensation assessment of UK miners. METHODS: Analysis of a subset of UK miners assessed at our unit, together with data from a small repeatability study of the standardized CPT in normal subjects. RESULTS: Rewarming time in the CPT was significantly lower in those subjects classified as vascular Stockholm stage 0 compared with Stockholm stages 1-3 combined, but did not discriminate between the stages of abnormality. Using the suggested cut-off in the CPT test, the sensitivity and specificity were calculated as 43 and 78%, respectively. Receiver operator characteristic analysis suggested that the rewarming time of highest accuracy gave a sensitivity of 66% and specificity of 59%. In 10 miners who reported unilateral hand blanching, there was no significant difference in CPT measurements between blanching and non-blanching hands. Repeat CPT measurements in normal subjects suggested mean differences of 52 and 107 s for each hand, and the Bland-Altman coefficient of repeatability was approximately 600 s for all fingers. CONCLUSION: Single application of this standardized CPT test may have limited value in diagnosing the vascular component of HAVS in an individual.

Adult↗
PubMed2002

The relation of White Matter Hyperintensities to implicit learning in healthy older adults.

OBJECTIVE: This study examined whether MRI evidence of cerebrovascular disease in the form of white matter hyperintensities (WMH) was associated with decreased implicit sequence learning performance in a high-functioning group of normal elderly volunteers. METHOD: One hundred and eight community-dwelling elderly individuals received an MRI and performed an implicit sequence learning task, the serial reaction time (SRT) task. RESULTS: Hyperintensities present in the white matter were associated with a decreased learning effect. This association was found with both deep white matter and periventricular changes. Other factors affecting SRT performance (i.e., baseline reaction time and switch-cost) were not significantly related to the presence of WMH. CONCLUSIONS: The results indicate that in addition to previously identified generalized cognitive deficits, WMH are also associated with a specific decrease in the implicit learning of sequences.

Aged↗
PubMed2002

Does weight loss improve incontinence in moderately obese women?

The aim of this study was to evaluate the effect of weight reduction on urinary incontinence in moderately obese women. This prospective cohort study enrolled moderately obese women experiencing four or more incontinence episodes per week. BMI and a 7-day urinary diary were collected at baseline and on the completion of weight reduction. The study included 10 women with a mean (+/-SD) baseline BMI of 38.3 (+/-10.1) kg/m2 and 13 (+/-10) incontinent episodes per week. Participants had a mean BMI reduction of 5.3 (+/-6.2) kg/ m2 (P < 0.03). Among women achieving a weight loss of > or = 5%, 6/6 had > or = 50% reduction in incontinence frequency compared to 1 in 4 women with < 5% weight loss (P < 0.03). Incontinence episodes decreased to 8 (+/-10) per week following weight reduction (P < 0.07). The study demonstrated an association between weight reduction and improved urinary incontinence. Weight reduction should be considered for moderately obese women as part of non-surgical therapy for incontinence.

Adult↗
PubMed2002

Clinical features and assessment of severe dementia. A review.

Sound understanding of the dementia syndrome requires adequate acquaintance with its entire spectrum, from the lightest to the most advanced stages. Most studies of dementia deal with light to moderate stages of the condition, while relatively little attention has been paid to its most severe stages. This review presents a clinical description of patients with severe dementia and of the tests currently available to evaluate their cognitive, behavioural, and functional status. Available instruments such as the Hierarchic Dementia Scale or the Severe Impairment Battery now allow quantification of the cognitive and behavioural status of patients with severe dementia. Experience with severe dementia shows that, far from being in a "vegetative state", as is commonly thought, late-stage patients are in fact quite different from one another and in most cases continue to have an interaction with their environment. This ability to better define the characteristics of patients with severe dementia provides the basis for correlations between clinical data and data derived from neuroimaging, neurochemistry, or neuropathology. It also sets the stage for possible therapeutic trials involving these patients.

Alzheimer Disease↗
PubMed2002

Cholinesterase inhibitor treatment alters the natural history of Alzheimer's disease.

OBJECTIVE: To describe the effect of cholinesterase inhibitors (CEIs) on the natural course of Alzheimer's disease (AD). METHODS: The short and long term effects of CEIs were evaluated in 135 patients with probable Alzheimer's disease relative to 135 patients who were never exposed to CEIs matched by age, education, duration of the symptoms, and cognitive status. We measured 1 year change in cognitive and functional performance, and the likelihood of arriving at each of four end points: (1) mini mental state examination (MMSE) of 9 or lower, (2) Blessed dementia rating scale for activities of daily living of 12 or higher, (3) nursing home admission, and (4) death, over an average 3 years of observation (36.7 (SD 21.5) months). RESULTS: Patients on CEIs were better cognitively and functionally after 1 year compared with those patients who never used CEIs. A proportional hazard analysis with CEI use as a time dependent covariate showed that the use of CEIs decreased the risk of nursing home admission. There was no association, however, between use of CEIs and time to cognitive and functional end points, or to death. CONCLUSIONS: This observational study showed that there was an initial cognitive and functional benefit from the use of CEIs in Alzheimer's disease, which waned as the disease progressed. However, the results suggest that there is a long term beneficial effect of the use of CEIs, as indicated by the delay in admission to nursing homes.

Aged↗
PubMed2001

Serum response factor cleavage by caspases 3 and 7 linked to apoptosis in human BJAB cells.

Apoptosis involves the cessation of cellular processes, the breakdown of intracellular organelles, and, finally, the nonphlogistic clearance of apoptotic cells from the body. Important for these events is a family of proteases, caspases, which are activated by a proteolytic cleavage cascade and drive apoptosis by targeting key proteins within the cell. Here, we demonstrate that serum response factor (SRF), a transcription factor essential for proliferative gene expression, is cleaved by caspases and that this cleavage occurs in proliferating murine fibroblasts and can be induced in the human B-cell line BJAB. We identify the two major sites at which SRF cleavage occurs as Asp(245) and Asp(254), the caspases responsible for the cleavage and generate a mutant of SRF resistant to cleavage in BJAB cells. Investigation of the physiological and functional significance of SRF cleavage reveals that it correlates with the loss of c-fos expression, whereby neither SRF cleavage fragment retains transcriptional activity. Moreover, the expression of a noncleavable SRF in BJAB cells suppresses apoptosis induced by Fas cross-linking. These results suggest that for apoptosis to proceed, the transcriptional events promoting cell survival and proliferation, in which SRF is involved, must first be inactivated.

3T3 Cells↗
PubMed2001

Alcohol dementia: "cortical" or "subcortical" dementia?

Most dementias are considered to exhibit either a predominantly "cortical" (e.g. Alzheimer's disease, AD) or "subcortical" (e.g. Parkinson's disease) pattern. A double dissociation has been reported, such that cortical and subcortical dementias can be differentiated based on performance on tests of declarative and procedural learning. The goal of this study was to determine if subjects with alcohol dementia exhibit a predominantly cortical or subcortical dementia profile. The performance of 10 elderly subjects diagnosed with alcohol dementia, 29 elderly subjects with histories of alcohol dependence but who were not demented, and 11 subjects with AD was compared to 20 elderly control subjects. The results indicated that the procedural learning task did not differentiate among the groups, whereas the discriminability index from the California Learning Test (the declarative learning task) did. Thus, alcohol dementia cannot clearly be ascribed to either dementia classification.

Journal Article↗
PubMed2001

Relationship of deep white matter hyperintensities and apolipoprotein E genotype to depressive symptoms in older adults without clinical depression.

OBJECTIVE: This study examined whether evidence of cerebrovascular disease in the form of magnetic resonance imaging (MRI) signal hyperintensities in white matter was associated with depressive symptoms in a high-functioning group of normal elderly volunteers. METHOD: Ninety-two community-dwelling elderly individuals participating in a study of white matter hyperintensities (WMHs) in normal aging whose apolipoprotein E (APOE) genotype had been determined completed the Geriatric Depression Scale and received an MRI scan. Univariate analyses of variance were used to examine the relationship between depressive symptoms and the location of WMHs (in deep white matter versus in periventricular white matter) and to determine whether WMHs were more likely to be associated with symptoms of impaired motivation and concentration or with mood symptoms. The effect on depressive symptoms of the interaction between severity of cerebrovascular disease as evidenced by WMHs and APOE genotype was also examined. RESULTS: Hyperintensities in the deep white matter, but not in the periventricular white matter, were associated with depressive symptoms, especially symptoms of impaired motivation, concentration, and decision making. The relationship between deep WMHs and depressive symptoms was especially strong in individuals carrying the APOE-4 allele. CONCLUSIONS: The pattern of depressive symptoms associated with WMHs in this study was similar to the pattern described in the literature as characterizing "vascular" depression in older persons with major depression. The results suggest that cerebrovascular disease may also underlie the depressive symptoms often found in older individuals who are not clinically depressed.

Aged↗
PubMed2000

Research evaluation and diagnosis of probable Alzheimer's disease over the last two decades: I.

OBJECTIVE: To describe the experience of a research clinic diagnosing AD during the last two decades, with special emphasis on patients who meet the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD, their patterns of clinical presentation, and neuropathologic outcomes. BACKGROUND: Probable AD has a heterogeneous clinical presentation, and can occur in the context of complicating factors. There are few reports, and none with this large of a sample, about the pattern of presentation, the nature of comorbidities, and the sensitivity and specificity of diagnosis. RESULTS: The AD Research Center of Pittsburgh examined 1139 patients with probable AD between April 1983 and February 2000. Of these 1139 probable AD patients, 29 (2.5%) had slow progression, 27 (2%) had rapid progression, 70 (6%) had an atypical presentation, and 85 (7%) had coexistent cerebrovascular disease. Confluent periventricular white matter lesions were found in 348 (30.5%) patients with probable AD. The overall sensitivity for the diagnosis of AD was 97% and the specificity 80%. However, the accuracy for the diagnosis of AD varied over the years: from 1983 to 1989, the sensitivity was 94% and specificity 52%, and from 1990 to 2000, the sensitivity was 98% and specificity 88%. CONCLUSION: Although the diagnosis of probable AD has been used to indicate the presence of a homogeneous clinical entity, these patients can vary in presentation, onset, or clinical course. This finding is of particular importance for the understanding of the pathophysiologic basis of the disease, and for the better identification of responders to dementia treatments. Although the sensitivity for the diagnosis of AD remained above 90% over the last two decades, the specificity increased, reflecting progressive improvement in the diagnosis of other dementing disorders.

Aged↗
PubMed2000

Research evaluation and diagnosis of possible Alzheimer's disease over the last two decades: II.

OBJECTIVE: To describe the experience of a research clinic diagnosing possible AD during the last two decades. BACKGROUND: The National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for possible AD are generally used to indicate that a patient has AD in association with another disease process that could by itself cause dementia. There are no studies describing how these criteria should be applied, and there are no descriptions of functional and cognitive progression or survival in possible AD. METHODS: The authors examined the clinical characteristics of 267 patients diagnosed with possible AD at the AD Research Center of Pittsburgh from 1983 to 2000 and the likelihood of arriving at four endpoints: Mini-Mental State Examination score of </= 9, Blessed Dementia Rating Scale for activities of daily living score of >/= 12, nursing home admission, and death. RESULTS: The possible AD classification has been simplified in six categories: possible AD with cerebrovascular disease (CVD) (69%), with history of alcohol abuse (15%), with history of depression (7%), with thyroid disease (4%), with history of head trauma (6%), with vitamin B12 deficiency (6%), and with other disease process that may have affected the clinical presentation of AD (4%). The presence of CVD, history of alcohol abuse, and history of depression concomitant with the onset of dementia were associated with time to death. Neither thyroid disease, history of head trauma, nor vitamin B12 deficiency were associated with any of the four endpoints. CONCLUSION: This cohort showed that comorbid conditions that can affect cognition delineate clearly defined subgroups in AD. The presence of environmental or other brain disorders sufficient to produce dementia appears to affect physical survival in patients with AD, but not functional and cognitive decline or institutionalization.

Aged↗
PubMed2000

Normative data on the Boston Naming Test and two equivalent 30-item short forms.

Because of the significance of the Boston Naming Test (BNT) in the differential diagnosis of the dementias, especially Alzheimer's disease, adequate norms from community-dwelling elderly individuals are essential. The present study describes the development of two new empirically derived equivalent short forms (30 items each) of the test. Normative data for the total BNT and the two equivalent 30-item halves based on item difficulty are presented using the performance of 314 community-dwelling individuals aged 65 and over. Age and education norms are presented using an overlapping midpoint interval strategy.

Aged↗
PubMed2000

Dynamic control and conventional strength ratios of the quadriceps and hamstrings in subjects with anterior cruciate ligament deficiency.

The hamstrings:quadriceps muscle strength ratio has been used as an indicator of normal balance between the knee flexors and extensors. A more functional approach to this strength ratio would be to compare opposite muscle actions of antagonistic muscle groups. The dynamic strength control ratio (DSCR) should give a more appropriate measure relating to knee function. There is a lack of normative data relating to DSCR for anterior cruciate ligament (ACL) deficient subjects. Effects of ACL deficiency on isokinetic peak torque for eccentric and concentric muscle actions of the quadriceps and hamstrings, in conjunction with isometric peak torque, were examined in 10 patients awaiting reconstructive surgery (male = 8, female = 2 ; age = 32.8 +/- 8.3 years; height = 1.77 +/- 0.08 m; mass = 72.1 +/- 12.5 kg). These variables were assessed using an isokinetic dynamometer. The results were considered in terms of the conventional ratio and DSCR. Anterior tibial drawer was measured using a knee ligament arthrometer to confirm clinical diagnosis of ACL rupture. The isokinetic peak torque data analysed were for angular velocities of 1.05 rad s(-1) (60 degrees s(-1)). Significant strength deficits were apparent between normal and injured sides for: concentric isokinetic quadriceps action (p < 0.05); isometric quadriceps action at 70 degrees of knee flexion (p < 0.05); isometric quadriceps action at 40 degrees of knee flexion (p<0.01); eccentric isokinetic hamstrings action (p < 0.05). With bilateral comparison, the conventional strength ratios showed no significant difference, as did the DSCR. The bilateral comparison of isometric strength ratios revealed significant losses in quadriceps strength for the injured side (p < 0.05) but no significant losses in hamstring strength (p > 0.05). Thus, differences can be seen in conventional ratios and DSCR for ACL-deficient subjects. This is an area of clinical interest with the increasing frequency of ACL reconstruction using hamstrings tendons.

Adult↗
PubMed2000

Alcohol, dementia, and Alzheimer's disease: comparison of neuropsychological profiles.

Thirty-nine detoxified elderly alcoholics (mean age = 65.85) completed a comprehensive assessment designed to identify individuals meeting DSM-IV criteria for alcohol-related dementia. Ten subjects meeting criteria (mean age = 69.8; mean Mini-Mental State Examination [MMSE] = 25.1) were compared to the 29 nondemented alcoholics (mean age = 64.5; mean MMSE = 27.8), 9 patients with Alzheimer's disease (mean age = 73.4; mean MMSE = 22.3), and 15 control subjects (mean age = 70.8; mean MMSE = 28). Comparison of neuropsychological test scores revealed several statistically significant differences. Furthermore, the overall pattern of test performance between the two demented groups was different. Alzheimer's patients were more impaired on confrontation naming, recognition memory, animal fluency, and orientation. Alcohol dementia subjects were more impaired than controls on initial letter fluency, fine motor control, and free recall. However, alcohol dementia subjects did not differ from controls on tests of verbal recognition memory. This study suggests that it is possible to clinically differentiate the cognitive deficits of alcohol-related dementia from typical Alzheimer's disease. However, the results are preliminary and are based on small sample sizes so should be interpreted with caution.

Aged↗
PubMed2000

Does paclitaxel improve the chemoradiotherapy of locoregionally advanced esophageal cancer? A nonrandomized comparison with fluorouracil-based therapy.

PURPOSE: A phase II trial of accelerated fractionation radiation with concurrent cisplatin and paclitaxel chemotherapy was performed to investigate the role of the paclitaxel, when substituted for fluorouracil (5-FU), in the chemoradiotherapy of esophageal cancer. PATIENTS AND METHODS: Patients with an esophageal ultrasound stage of T(3) or N(1) or M(1) (nodal) esophageal cancer were treated with two courses of a cisplatin infusion (20 mg/m(2)/d for 4 days) and paclitaxel (175 mg/m(2) over 24 hours) concurrent with a split course of accelerated fractionation radiation (1.5 Gy bid to a total dose of 45 Gy). Surgical resection was performed 4 to 6 weeks later followed by a single identical postoperative course of chemoradiotherapy (24 Gy) in patients with significant residual tumor at surgery. Toxicity and results of this treatment were retrospectively compared with our previous 5-FU and cisplatin chemoradiotherapy experience. RESULTS: Between September 1995 and July 1997, 40 patients were entered onto this study. Although dysphagia proved worse in our 5-FU-treated patients, profound leukopenia and a need for unplanned hospitalization were significantly more common in the paclitaxel group. Thirty-seven patients (93%) proved resectable for cure. The 3-year projected overall survival is 30%, locoregional control is 81%, and distant metastatic disease control is 44%. When compared with a similarly staged cohort of 5-FU-treated patients, there was no advantage for any survival function studied. CONCLUSION: This paclitaxel-based treatment regimen for locoregionally advanced esophageal cancer produced increased toxicity with no improvement in results when compared with our previous 5-FU experience. Paclitaxel-based treatments must be carefully and prospectively studied before their incorporation into the standard management of esophageal cancer.

Adult↗
PubMed2000

The neuropsychological consequences of abstinence among older alcoholics: a cross-sectional study.

BACKGROUND: The older alcoholic has been distinguished from the younger alcoholic with regard to both the acute effects of alcohol and also the recovery of functioning with abstinence. Few studies, however, have included samples of exclusively older subjects. In this investigation we examined the recovery of functioning in an older cohort of recovering alcoholics (age range 55-83) to determine which neuropsychological functions improve and which remain impaired with abstinence. METHODS: We used a cross-sectional design, comparing three demographically matched groups on a battery of neuropsychological tests: (a) older alcoholics who had been abstinent for greater than 6 months, (b) older alcoholics who had been abstinent for less than 6 months, and (c) a control group of older subjects without alcohol abuse histories. RESULTS: In almost all tasks, the alcoholics who were abstinent for less than 6 months performed worse than the control group. In contrast, the alcoholics who had been abstinent for more than 6 months differed from the control group on learning and recall of a word list, immediate and delayed recall of a complex figure, initial letter fluency, and clock drawing. CONCLUSIONS: Memory and executive skills appear to be resistant to recovery or at least slower to recover with abstinence in the older alcoholic. The impairment with visuospatial skills reported in prior investigations of alcoholics may be related to compromised executive functions, which interfere with the encoding of more complex visuospatial information and thus affect recall of such information. Studies that involve larger samples of older alcoholics are needed to understand their ability to recover cognitive functioning with abstinence.

Aged↗