Brain volume loss in MCI predicts dementia.
Rates of temporal horn volume change were significantly greater in the subjects with mild cognitive impairment who were developing dementia vs those who remained stable.
Aged↗
Biomedical subjects
G Sexton
Publications and source records attributed to G Sexton.
Asynchronous regional brain volume losses in presymptomatic to moderate AD.
To determine if rates and locations of brain volume loss associated with AD are phase-specific, occurring prior to clinical onset and at later stages, we performed longitudinal volumetric MRI analysis on 155 subjects enrolled in a prospective study of aging and dementia. Subjects were divided by Clinical Dementia Rating (CDR) scale into stages of Normal (CDR 0 --> 0), Very Mild (CDR 0 --> 0.5 and 0.5 --> 0.5), Mild (CDR 0.5 --> 1.0 and 1.0 --> 1.0) and Moderate (CDR 1.0 --> 2.0 and 2.0 --> 2.0) dementia. Rates of volume change in CSF spaces, lobar and medial temporal lobe regions were analyzed for group differences across stages. Annual rates of ventricular volume change differed between non-demented and very mild group (p<0.01). In later severity stages, ventricular, temporal, basal ganglia-thalamic region and total volumes show change. Rates of volume loss increase as dementia progresses, but not uniformly in all regions. These regional and phase-specific volume changes form targets for monitoring disease-modifying therapies at clinically relevant, defined stages of dementia.
Aged↗
Changes in premorbid brain volume predict Alzheimer's disease pathology.
OBJECTIVE: To assess whether changes in antemortem MRI brain volume measurements are valid predictors of subsequent Alzheimer disease (AD) pathology. METHODS: Thirty-nine subjects, 15 nondemented and 24 with cognitive impairment, were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to cross-sectional and longitudinal volumetric measurements obtained from antemortem MRI. RESULTS: Total brain volume change over time was related to the accumulation of cortical NFT. The rate of ventricular CSF volume increase was related to both cortical NFT and SP. The last hippocampal volume prior to death was related to hippocampal NFT burden; the rate of hippocampal volume atrophy was not related to hippocampal NFT pathology. These significant relationships continue to exist when all nondemented subjects are excluded from analysis. In subjects with cognitive impairment, the best predictor of cortical NFT and SP is the rate of ventricular volume increase. Excluding subjects with long duration between MRI and death did not appreciably alter results. CONCLUSIONS: MRI volumes measured over time are valid biomarkers of pathologic progression of AD across a range of antemortem clinical states. The rate of ventricular volume enlargement can be used to monitor disease progression or response to treatment in future clinical trials that are targeted at NFT and SP pathology.
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Natural history of cognitive decline in the old old.
OBJECTIVE: To prospectively examine the occurrence and outcome of cognitive decline in healthy, community-dwelling elders. METHODS: Ninety-five elders (mean age 84 years) who at entry had no cognitive impairment were followed for up to 13 years. Cognitive decline was defined as obtaining either a Clinical Dementia Rating (CDR) = 0.5 or Mini-Mental State Examination (MMSE) score < 24 on two examinations. RESULTS: Three outcomes of aging were determined: intact cognition, persistent cognitive decline without progression to dementia, and dementia. Whereas 49% remained cognitively intact, 51% developed cognitive decline. Mean follow-up to first CDR 0.5 was 3.8 years and age at conversion was 90.0 years. Those who remained cognitively intact had better memory at entry and were less likely to have APOE4 than those who developed cognitive decline. Of the 48 participants with cognitive decline, 27 (56%) developed dementia (CDR > or =1) a mean of 2.8 years later. Participants with cognitive decline who progressed to dementia had poorer confrontation naming at the time of their first CDR 0.5 than those with persistent cognitive decline who did not progress during follow-up. CONCLUSION: The old old are at high risk for developing cognitive decline but many will not progress to dementia in the next 2 to 3 years or even beyond. These findings are important for understanding the prognosis of cognitive decline and for the design of treatment trials for AD. APOE genotype is a risk factor for cognitive decline.
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Evaluation of the THINK FIRST For KIDS injury prevention curriculum for primary students.
THINK FIRST is a national non-profit organization whose mission is to educate young people about the prevention of brain and spinal cord injuries. This paper describes a study conducted by THINK FIRST of Oregon on one of its injury prevention curricula, THINK FIRST for KIDS.
Accident Prevention↗
Parkinson's disease, CYP2D6 polymorphism, and age.
OBJECTIVE: PD may be caused by genetic susceptibility to neurotoxins. CYP2D6 is a candidate gene for PD because it regulates drug and toxin metabolism, but association studies have been inconsistent. The aim of this study was to test if the CYP2D6*4 allele (poor metabolizer phenotype) is associated with earlier age at onset. METHODS: Five hundred seventy-six patients with PD and 247 subjects without PD were studied using standard diagnostic, genotyping, and statistical techniques. RESULTS: Surprisingly, mean onset age was significantly later in *4-positive patients. Frequency of *4 was significantly higher in late-onset PD than early-onset PD. When early- and late-onset PD were analyzed separately, *4 had no effect on onset age; hence, the association with delayed onset was likely an artifact of an elevated *4 frequency in late-onset PD. Contrary to a common assumption that CYP2D6 frequencies do not change with age, *4 frequency rose significantly with advancing age, both in patients with PD (from 0.16 at mean age of 56.5 years to 0.21 at mean age of 72) and subjects without PD (from 0.09 at mean age of 45.5 years to 0.21 at mean age of 72). *4 Frequencies in patients with early- and late-onset PD, although different from each other, were in agreement with similarly aged subjects without PD, suggesting the elevated *4 frequency in late-onset PD was likely an age effect, unrelated to PD. CONCLUSION: The CYP2D6*4 allele is not associated with earlier PD onset. *4 May be associated with survival. Inconsistent results from allelic association studies may have been due to an unrecognized age effect.
Age of Onset↗
Exacerbated physical fatigue and mental fatigue in Parkinson's disease.
OBJECTIVE: To characterize fatigue in Parkinson's disease (PD). BACKGROUND: Fatigue is a recognized problem in PD. Fatigue can be in the physical realm or in the mental realm. Fatigue has not been characterized in PD. METHODS: We characterized fatigue in 39 PD patients and 32 age-matched normal controls using five questionnaires: A. The Multidimensional Fatigue Inventory (MFI), which measures five dimensions of fatigue independently including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. B. The Fatigue Severity Inventory (FSI), which quantifies fatigue in general. C. The Profile of Mood States (POMS), which assesses six subjective subscales: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, vigor-activity, and confusion-bewilderment. D. Center for Epidemiological Studies-Depression Scale (CES-D). E. Visual Analog linear scale of energy (VA-E). RESULTS: PD patients scored higher in all of the five dimensions of fatigue in the MFI including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue (P < 0.001 except for mental fatigue P = 0.005). The severity of physical fatigue did not correlate with that of mental fatigue. PD patients scored higher on the FSI, POMS, CES-D, and scored lower on the VA-E. The scores in the FSI correlated with general fatigue, physical fatigue, reduced activity, and reduced motivation but not with mental fatigue in the MFI. Depression correlated with all dimensions of fatigue except physical fatigue in the MFI. Disease severity, as measured by Modified Hoehn and Yahr staging, did not correlate with any of the measures. CONCLUSIONS: PD patients have increased physical fatigue and mental fatigue compared to normals. Physical fatigue and mental fatigue are independent symptoms in PD that need to be assessed and treated separately.
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Patient characteristics and physicians' practice activities for patients with chronic low back pain: a practice-based study of primary care and chiropractic physicians.
BACKGROUND: Chronic low back pain sufferers are among those who account for the greatest usage of health care resources. Primary care medical (MD) physicians and chiropractic (DC) physicians treat most of these patients. OBJECTIVES: To study patient characteristics and physician practice activities for patients with chronic low back pain treated by DC physicians and MD physicians. METHODS: A longitudinal, practice-based observational study was undertaken in 14 general practice and 51 DC community-based clinics. A total of 2945 consecutive patients with ambulatory low back pain of mechanical origin were enrolled; 835 patients were in the chronic subgroup. Patients were followed for 12 months. Data were obtained on all of the following: patient demographics, health status, and psychosocial characteristics; history, duration, and severity of low back pain and disability; physicians' practice activities; and low back complaint status at 1 year. RESULTS: Patients treated by MD physicians were younger and had lower incomes; their care was more often paid for by a third party; their baseline pain and disability were slightly greater. In addition, patients treated by MD physicians had one fourth as many visits as patients treated by DC physicians. Utilization of imaging procedures by enrolling physicians was equivalent for the two provider groups. Medications were prescribed for 80% of the patients enrolled by MD physicians; spinal manipulation was administered to 84% of patients enrolled by DC physicians. Physical modalities, self-care education, exercise, and postural advice characterized low back pain management in both provider groups. Patients' care-seeking was not exclusive to one provider type. Most patients experienced recurrences (patients treated by MD physicians, 59.3%; patients treated by DC physicians, 76.4%); 34.1% of patients treated by MD physicians and 12.7% of patients treated by DC physicians reported 12 months of continuous pain. Only 6.7% of patients treated by MD physicians and 10.9% of patients treated by DC physicians reported 1 resolved episode during the year. CONCLUSIONS: Differences in sociodemographics, present pain intensity, and functional disability may distinguish patients with chronic low back pain seeking care from primary care medical physicians from those seeking care from DC physicians. Although the primary treatment modality differs, the practice activities of MD physicians and DC physicians have much in common. Long-term evaluation suggests that chronic back pain is persistent and difficult to treat for both provider types.
Adult↗
Memory testing in dementia: how much is enough?
Analyses of eight widely used memory measures (Word List Acquisition and Recall used in the Alzheimer's Disease Assessment Scale and the Consortium to Establish a Registry for Alzheimer's Disease neuropsychology battery, Wechsler Memory Scale-Revised [WMS-R] Logical Memory I and II, WMS-R Visual Reproduction I and II, the memory scores from the Neurobehavioral Cognitive Status Examination [NCSE], memory scores from the Mini-Mental State Examination [MMSE]), and the MMSE total score showed each to have moderate predictive power in differentiating between patients with mild dementia and healthy normal controls. When these instruments were combined in a logistic regression analysis, three of them had substantial predictive power. Together, the Word List Acquisition, WMS-R Logical Memory II, and WMS-R Visual Reproduction II were 97.26% accurate (100% sensitive and 94.59% specific) in distinguishing these two groups. The Word List Acquisition is a brief test that alone had high accuracy (92%). These memory tests are highly useful in the diagnosis of mild dementia.
Aged↗
Pain, disability, and satisfaction outcomes and predictors of outcomes: a practice-based study of chronic low back pain patients attending primary care and chiropractic physicians.
BACKGROUND: Few studies exist on the prognostic value of demographic, clinical, or psychosocial factors on long-term outcomes for patients with chronic low back pain. OBJECTIVE: This study reports on long-term pain and disability outcomes for patients with chronic low back pain, evaluates predictors of long-term outcomes, and assesses the influence of doctor type on clinical outcome. METHODS: Sixty chiropractic (DC) and 111 general practice (MD) physicians participated in data collection for a prospective, longitudinal, practice-based, observational study of ambulatory low back pain of mechanical origin. The primary outcomes, measured at 6 months and 12 months, were pain (by using the Visual Analog Scale), and functional disability (by using the Revised Oswestry Disability Questionnaire). Satisfaction was a secondary outcome. RESULTS: Overall, long-term pain and disability outcomes were generally equivalent for patients seeking care from medical or chiropractic physicians. Medical and chiropractic care were comparable for patients without leg pain and for patients with leg pain above the knee. However, an advantage was noted for chronic chiropractic patients with radiating pain below the knee after adjusting for baseline differences in patient and complaint characteristics between MD and DC cohorts (adjusted differences = 8.0 to 15.2; P <.002). A greater proportion of chiropractic patients were satisfied with all aspects of their care (P =.0000). The strongest predictors of primary outcomes included an interaction of radiating pain below the knee with provider type and baseline values of the outcomes. Income, smoking, comorbidity, and chronic depression were also identified as predictors of outcomes in this study. CONCLUSION: Chiropractic care compared favorably to medical care with respect to long-term pain and disability outcomes. Further study is required to explore the advantage seen for chiropractic care in patients with leg pain below the knee and in the area of patient satisfaction. Identification of patient and treatment characteristics associated with better or worse outcomes may foster changes in physicians' practice activities that better serve these patients' needs.
Adult↗
Premenopausal black women are uniquely at risk for coronary heart disease compared to white women.
Premenopausal black women have a two to threefold greater rate of coronary heart disease than premenopausal white women. This study was designed to provide greater insight into the reasons for this difference which is currently unclear. Coronary heart disease risk factors were compared in 100 black and 100 white, healthy premenopausal women, ages 18-45 years, and of relatively advantaged socioeconomic status. Compared to white women, black women had a higher body mass index (32.0±9.2 vs. 29.0±9.4 kg/m2, p=0.021), and higher systolic (124±17 vs. 115±14 mm Hg, p<0.0001) and diastolic (79±14 vs. 75±11 mm Hg, p=0.048) blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher in the black women (40.2±31.3 mg/dL) than in the white women (19.2±23.7 mg/dL, p<0.0001). The plasma total homocysteine level was also higher in the black women (8.80±3.38 vs. 7.81±2.58 mmol/L, p=0.013). The black women, however, had lower plasma triglyceride levels (0.91±0.46 vs. 1.22±0.60 mmol/L, p<0.0001) and a trend toward higher high-density lipoprotein cholesterol levels (1.37±0.34 vs. 1.29±0.31 mmol/L, p=0.064) than the white women. Plasma total and low-density lipoprotein cholesterol levels were similar. Black women consumed more saturated fat and cholesterol. Rates of cigarette smoking and alcohol intake were low and similar between the races. In summary, compared to white women, black women had a higher mean body mass index, higher blood pressures, higher lipoprotein(a) and plasma total homocysteine levels, and greater consumption of saturated fat and cholesterol. The differences in coronary risk factors between these two premenopausal groups may explain the higher incidence of coronary heart disease in black women. (c) 2000 by CHF, Inc.
Journal Article↗
Longitudinal analysis of the effects of the aging process on neuropsychological test performance in the healthy young-old and oldest-old.
A sample of 33 young-old (ages 65 to 74) and 20 oldest-old (ages 84 to 93) healthy elderly without dementia were assessed with neuropsychological tests annually over a 4-year period to examine longitudinal changes in cognitive functioning. Significant age-group differences existed at baseline in participants' performances on tests of immediate memory and visuospatial skills. There were no age-group differences in the rate of change over the 4-year interval on any neuropsychological tests. Within each age-group, the amount of change over time was minimal for most tests though some practice effects were apparent, and on some tests mild decline was observed. Results suggest that healthy old adults, including the oldest-old, do not experience measurable declines in cognitive functioning over a 4-year period.
Age Factors↗
Higher total homocysteine concentrations and lower folate concentrations in premenopausal black women than in premenopausal white women.
BACKGROUND: Premenopausal black women have a greater rate of coronary artery disease (CAD) than do premenopausal white women. Plasma total homocysteine concentrations, a risk factor for CAD, have not been reported in premenopausal black women. OBJECTIVE: The purpose of this study was to compare plasma total homocysteine, folate, and vitamin B-12 concentrations in premenopausal black and white women. DESIGN: Eighty-nine black and 90 white, healthy, premenopausal women living in Portland, OR, were recruited. Dietary histories were obtained by using the Diet Habit Survey, a 40-item eating-behavior questionnaire. Plasma concentrations of total homocysteine, folate, and vitamin B-12 were measured. RESULTS: Black women had higher plasma total homocysteine (8.32 compared with 7.60 micromol/L;P = 0. 013), lower plasma folate (6.62 compared with 9.88 nmol/L;P < 0. 0001), and higher vitamin B-12 (355 compared with 283 pmol/L;P < 0. 001) concentrations than white women. White women had a greater rate of daily multivitamin supplement use (42.4% compared with 24.7%;P = 0.019) and ate more ready-to-eat cereal than did black women. After adjustment for multivitamin use and intake of ready-to-eat cereal, plasma total homocysteine concentrations did not differ significantly, but plasma folate remained significantly lower in the black women. None of the black women but 12.3% of the white women (P = 0.013) were homozygous for the cytosine to thymidine mutation at nucleotide 677 in the methylenetetrahydrofolate reductase gene. CONCLUSIONS: Black women had higher plasma total homocysteine and lower plasma folate concentrations than white women, largely because of lifestyle factors, which may contribute to the greater rate of CAD in premenopausal black than in white women.
Adolescent↗
Factors associated with brain donation among optimally healthy elderly people.
BACKGROUND: Consent rates for brain donation were examined in 140 healthy elderly participants of the Oregon Brain Aging Study, a longitudinal study of successful aging. Subjects were initially selected for good health. The study population had a relatively high education level, a high socioeconomic status, and were predominantly white. METHODS: At each annual examination, a project physician asked participants to consider brain donation. This analysis examined variables that may affect the rate of brain donation consent: age, gender, education, socioeconomic status, marital status, religiosity, cognitive status, depression, and functional status. RESULTS: Of these variables only age was a meaningful factor. CONCLUSION: The oldest old participants (> or =85 years of age) were more likely to consent to donation than the younger participants (65-84 years of age).
Age Factors↗
The influence of anesthetic choice, PaCO2, and other factors on osmotic blood-brain barrier disruption in rats with brain tumor xenografts.
UNLABELLED: Increasing the delivery of therapeutic drugs to the brain improves outcome for patients with brain tumors. Osmotic opening of the blood-brain barrier (BBB) can markedly increase drug delivery, but achieving consistent, good quality BBB disruption (BBBD) is essential. We evaluated four experiments compared with our standard isoflurane/O2 protocol to improve the quality and consistency of BBBD and drug delivery to brain tumor and normal brain in a rat model. Success of BBBD was assessed qualitatively with the large molecular weight marker Evans blue albumin and quantitatively by measuring delivery of the low molecular weight marker [3H]-methotrexate. With isoflurane/O2 anesthesia, the effects of two BBBD drugs of different osmolalities were evaluated at two different infusion rates and infusion durations. Arabinose was superior to saline (P = 0.006) in obtaining consistent Evans blue staining in 16 of 24 animals, and it significantly increased [3H]-methotrexate delivery compared with saline in the tumor (0.388 +/- 0.03 vs 0.135 +/-0.04; P = 0.0001), brain around the tumor (0.269 +/- 0.03 vs 0.035 +/- 0.03; P = 0.0001), brain distant to the tumor (0.445 +/- 0.05 vs 0.034 +/- 0.07; P = 0.001), and opposite hemisphere (0.024 +/- 0.00 vs 0.016 +/- 0.00; P = 0.0452). Forty seconds was better than 30 s (P = 0.0372) for drug delivery to the tumor. Under isoflurane/O2 anesthesia (n = 30), maintaining hypocarbia was better than hypercarbia (P = 0.025) for attaining good BBBD. A propofol/ N2O regimen was compared with the isoflurane/O2 regimen, altering blood pressure, heart rate, and PaCO2 as covariates (n = 48). Propofol/N2O was superior to isoflurane/O2 by both qualitative and quantitative measures (P < 0.0001). Neurotoxicity and neuropathology with the propofol/N2O regimen was evaluated, and none was found. These data support the use of propofol/N2O along with maintaining hypocarbia to optimize BBBD in animals with tumors. IMPLICATIONS: Propofol/N2O anesthesia may be better than isoflurane/O2 for optimizing osmotic blood-brain barrier disruption for delivery of chemotherapeutic drugs to brain tumor and normal brain.
Anesthetics, Inhalation↗
Age-related brain changes associated with motor function in healthy older people.
OBJECTIVE: To identify the MRI imaging findings associated with motor changes in healthy older people. DESIGN: A cross-sectional study. SETTING: A study of neurologic function in very healthy older people, the Oregon Brain Aging Study. PARTICIPANTS: Clinical and MRI data were examined in 50 very healthy older subjects (mean age = 85.1, SD = 7.2 years). MEASUREMENTS: Clinical measures (finger tapping, hand opening and closing, steps and time to walk 30 feet and timed standing on one foot) were dependent variables in multiple regression analyses using age and the following MRI measures as independent variables: total brain volume (TBV)/intracranial volume; ventricular volume/TBV; periventricular high signal/TBV; deep high signal/TBV. RESULTS: The number of steps and the time to walk 30 feet were each associated with periventricular high signal (steps: r = .58, P < .001; time: r = .60, P < .001) and ventricular volume (steps: r = .54, P < .001; time: r = .58, P < .001). These associations remained significant after adjusting for age. None of the other clinical variables was associated with the MRI volumes. CONCLUSIONS: Gait measures were associated significantly with periventricular high signal and ventricular volume. These CNS changes contribute to the cause of these important markers of aging.
Aged↗
Premenopausal black women have more risk factors for coronary heart disease than white women.
Premenopausal black women have a 2- to 3-fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide greater insight into the reasons for this difference, which are currently unclear. We compared CHD risk factors in 99 black and 100 white, healthy premenopausal women, aged 18 to 45 years, and of relatively advantaged socioeconomic status. Compared with white women, black women had a higher body mass index (32.0 +/- 9.2 vs 29.0 +/- 9.4 kg/m2, p = 0.021), and higher systolic (124 +/- 17 vs 115 +/- 14 mm Hg, p <0.0001) and diastolic (79 +/- 14 vs 75 +/- 11 mm Hg, p = 0.048) blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher in the black women (40.2 +/- 31.3 mg/dl) than in the white women (19.2 +/- 23.7 mg/dl, p <0.0001). The plasma total homocysteine level was also higher in the black women (8.80 +/- 3.38 vs 7.81 +/- 2.58 micromol/L, p = 0.013). The black women, however, had lower plasma triglyceride levels (0.91 +/- 0.46 vs 1.22 +/- 0.60 mmol/L, p <0.0001), and a trend toward higher high-density lipoprotein (HDL) cholesterol levels (1.37 +/- 0.34 vs 1.29 +/- 0.31 mmol/L, p = 0.064) than the white women. Plasma total and low-density lipoprotein (LDL) cholesterol levels were similar, despite a greater consumption of saturated fat and cholesterol by the black women. Rates of cigarette smoking and alcohol intake were low and similar between the races. In summary, premenopausal black women had a higher mean body mass index, blood pressure, lipoprotein(a), and plasma total homocysteine level, and a greater consumption of saturated fat and cholesterol than white women. These differences in coronary risk factors may place the black women in our study at increased risk for CHD compared with the white women.
Adolescent↗
Verbal fluency task affects gait in Parkinson's disease with motor freezing.
We examined the effects of a simultaneous verbal fluency task on walking in Parkinson's disease (PD) patients with freezing of gait (PD-F) compared to nonfreezing patients (PD-NF) or control subjects (C). Effects of antiparkinsonian medications on gait in PD-F were examined. PD-F patients exhibited a greater increase in the number of steps to complete the walk with verbal fluency, even when the effect of medication was taken into account (mean increase +/- SD): PD-F = 4.2 +/- 4.6, n = 10; PD-NF = 0.1 +/- 1.6, n = 9; C = 1.5 +/- 1.5, n = 19; P = .007. Medications improved walking in PD-F patients by decreasing the number of steps, the time to walk, and freezing. PD-F patients may be more dependent on attention for walking.
Aged↗