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J W Ashford

Publications and source records attributed to J W Ashford.

At least 19 recordsLinked to original sources
PubMed2006

Spatial test for agricultural pesticide "blow-in" effect on prevalence of Parkinson's disease.

The current study used Department of Veteran's Affairs (VA) clinical records, State of California pesticide application records, spatial maps of distribution of Parkinson's disease patients, and pesticide applications to determine if there was evidence for "blow-in" of pesticides as a factor in explaining the prevalence of Central Valley Parkinson's disease. The results did not support the hypothesis of increasing prevalence of Parkinsonism attributable to wind drift.

Agriculture↗
PubMed2004

Use of a VA pharmacy database to screen for areas at high risk for disease: Parkinson's disease and exposure to pesticides.

The purpose of this study was to assess whether pharmacy database information from US Department of Veterans Affairs (VA) medical centers could be used to screen for areas of higher Parkinson's disease prevalence in patients exposed to pesticides. The authors used pharmacy data sets and compared the use of antiparkinsonian medications at 2 VA medical centers in California: one in Palo Alto, near the ocean, and one in Fresno, downwind from extensively farmed parts of the Central Valley. They found that patients at Fresno had higher odds ratios (1.5-1.8) for the use of Parkinson's disease medications than patients at Palo Alto. These data are consistent with the observations of prior epidemiologic studies and suggest that VA pharmacy databases can prioritize locations for further epidemiologic research. However, a thorough exploration of alternative explanations is needed to reach definitive conclusions regarding the findings suggested by this method.

Antiparkinson Agents↗
PubMed2002

Measuring cognition in advanced Alzheimer's disease for clinical trials.

Measurement of cognitive dysfunction and treatment response in the early stages of Alzheimer's disease (AD) has used such scales as the Mini-Mental State Examination (MMSE) and the AD Assessment Scale (ADAS). With the exception of clinical rating scales, however, there are only a few objective measures of cognition for tracking progression in advanced AD. Given renewed interest in potential therapies for advanced AD, objective measures of cognition are important for the adequate evaluation of change due to AD progression or therapy. Several cognitive measures for advanced AD are reviewed. One measure, the Severe Impairment Battery (SIB) is reviewed in detail. Preliminary analyses from a trial of memantine show significant change on the SIB in memory (p < 0.001) and visuospatial functions (p < 0.02) over six-months with a trend for language and praxis. Data from a donepezil trial also highlight the importance of accurate assessment in advanced AD.

Aged↗
PubMed2001

Modeling the time-course of Alzheimer dementia.

Alzheimer's disease (AD) progresses from a preclinical period, through a middle phase of cognitive deterioration, to a late, profound state. The temporal progression of disability can be modeled with a horologic (time-based) function using "time-index" (TI) intervals (day- or year-units) to quantify an individual's disability across multiple cognitive and functional domains relative to a reference AD population. Clinicians and researchers can use TI quantification to assess dementia severity and initial therapy benefits. Rate of progression and confidence intervals require at least two successive measurements. Rate of progression measures can be used to support diagnosis and to investigate disease-course-modifying therapies.

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PubMed2000

"Preclinical" AD revisited: neuropathology of cognitively normal older adults.

OBJECTIVE: To classify neuropathologic alterations in the brains of nondemented older adults using current sets of criteria for AD. BACKGROUND: AD neuropathologic alterations are found in the brains of some nondemented elderly subjects and suggest the possibility of presymptomatic AD. Three sets of guidelines have been developed to classify AD using senile plaques, neuritic plaques, and neurofibrillary tangles (NFT). METHODS: Neuropathologic changes in 59 older adults followed longitudinally with a standard battery of mental status measures were investigated using Khachaturian, Consortium to Establish a Registry for Alzheimer's Disease (CERAD), and National Institute on Aging-Reagan Institute (NIA-RI) guidelines. AD neuropathologic markers were evaluated in neocortical and allocortical regions. Cases were categorized as neuropathologically "normal" or "AD-like" and compared for possible mental status differences. RESULTS: Between 11 and 49% of cases met one or more of the three classifications of AD. With adjustments for multiple comparisons, only NFT in hippocampal CA1 region were associated with autopsy age, suggesting that this may represent a pathologic process associated with normal brain aging. Using the NIA-RI guidelines, subjects in the AD-like group performed less well on the immediate paragraph recall and word-list delayed recall than their counterparts who did not meet these guidelines. CONCLUSIONS: These data indicate that the prevalence of "preclinical" AD in our population is relatively low based on the NIA-RI classification. Although many subjects had AD-like changes based on CERAD and Khachaturian guidelines, they exhibited no differences in mental performance, suggesting that the aging brain may be able to withstand such structural changes without meaningful impact on mental functioning.

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PubMed2000

Single SPECT measures of cerebral cortical perfusion reflect time-index estimation of dementia severity in Alzheimer's disease.

UNLABELLED: To determine the relationship between cerebral cortical blood flow loss and the temporal development of the dementia in Alzheimer's disease (AD), SPECT was studied in a cross section of AD patients with a broad range of impairment. METHODS: Thirty patients with a diagnosis of probable AD had their mini-mental state examination scores transformed into time-index values to give an estimation of dementia severity relative to the developmental time course. SPECT images were obtained using 99mTc-ethyl cysteinate dimer and a 3-head camera. Cortical surface perfusion was analyzed, including modified Talairach standardization, to obtain cortical elements from the convexity (each representing about 0.25 cm2 at the surface, 6.6-mm cortical depth) referenced to the mean perfusion of the full greater cerebellar hemisphere. These element ratios were analyzed (individually and by averages of estimated Brodmann's areas and brain regions) using linear regression with the time-index value. RESULTS: For individual posterotemporal and inferoparietal Brodmann's areas (21, 22 and 39, 40, respectively) the correlation coefficients between cortical perfusion ratios and dementia severity ranged between -0.67 and -0.78 (P < 0.001). Perfusion ratios from these regions declined 2.5%-4.2% for each estimated year of progression. Prefrontal area perfusion showed less association with severity. Perfusion in primary cortical regions had no significant association with dementia severity. CONCLUSION: Cerebral cortical perfusion loss is temporally related to development of dementia. The spatial pattern of high, significant correlations between cortical perfusion and dementia severity shows a regional distribution that corresponds closely to the distribution of AD pathology described in autopsy studies.

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PubMed1998

Pharmacokinetics, pharmacodynamics, and safety of metrifonate in patients with Alzheimer's disease.

Metrifonate is converted nonenzymatically to 2.2, dimethyl dichlorovinyl phosphate (DDVP), an inhibitor of acetylcholinesterase (AChE). This 21-day, randomized, double-blind, placebo-controlled trial of metrifonate in patients with Alzheimer's disease (n = 27) evaluated four doses, each administered orally once daily. All patients received a loading dose (LD) for 6 days followed by a maintenance dose (MD) for 15 days. The treatment groups were: panel 1, LD = 1.5 mg/kg (75-135 mg), MD = 0.25 mg/kg (12.5-25 mg); panel 2, LD = 2.5 mg/kg (125-225 mg), MD = 0.40 mg/kg (20-35 mg); panel 3, LD = 4.0 mg/kg (200-335 mg), MD = 0.65 mg/kg (30-60 mg); and panel 4, LD = 4.0 mg/kg (200-335 mg), MD = 1.0 mg/kg (50-90 mg). All metrifonate doses were well tolerated. Most adverse events were mild to moderate in intensity, gastrointestinal in nature, and transient. Mean area under the concentration-time curve (AUC) and maximum concentration (Cmax) for both metrifonate and DDVP increased in relation to dose. Metrifonate and DDVP had similar, largely dose-independent mean values for time to Cmax (tmax) and half-life (t1/2). There was little or no accumulation of either metrifonate or DDVP with long-term administration. After 21 days of treatment, mean percent erythrocyte AChE inhibition was 14%, 35%, 66%, 77%, and 82% for placebo and panels 1 through 4, respectively. Cognitive improvement was observed with the two highest metrifonate doses. These results reflect favorable safety and pharmacokinetic profiles for the use of metrifonate in the treatment of Alzheimer's disease.

Acetylcholinesterase↗
PubMed1998

Neuropil threads are collinear with MAP2 immunostaining in neuronal dendrites of Alzheimer brain.

Alzheimer disease (AD) neuropathology includes neuropil threads (NTs) and neurofibrillary tangles (NFTs). In tangle-bearing neurons, the normal cytoskeleton is severely disrupted and replaced with paired helical filament (PHF) aggregates of aberrantly phosphorylated microtubule-associated protein tau. In this study, double-label immunocytochemistry was used to clarify the relationship between the appearance of neurofibrillary pathology (NTs and NFTs) and the loss of normal cytoskeletal components, such as microtubule-associated protein 2 (MAP2) in 13 AD cases and 6 nondemented elderly control individuals. Brain areas examined included neocortex (cingulate, motor, and inferior parietal cortices), hippocampus, and entorhinal cortex. In mildly affected neurons, PHF-1 immunostained NTs were found in dendrites, frequently at dendritic branch points, and were adjacent to MAP2 immunostaining. In more severely affected neurons, the PHF-1 immunoreactivity occupied distinct dendritic segments and appeared to displace MAP2. Interspersed MAP2 immunopositive dendritic segments were often beaded in appearance. In all instances where dendrites with NTs could be traced back to the soma, the soma also contained PHF-1 immunostained fibrils in various stages of NFT formation. The results suggest that PHFs gradually displace normal microtubules in dendrites, and cause degeneration of dendritic segments between NTs.

Aged↗
PubMed1996

Age, education, and changes in the Mini-Mental State Exam scores of older women: findings from the Nun Study.

OBJECTIVE: To describe the relationship of Mini-Mental State Exam (MMSE) scores and changes over time in MMSE scores to age and education in a population of older women. DESIGN: A prospective study of a defined population. SETTING: Various motherhouses and church-run health care facilities in the Eastern, Midwestern, and Southern regions of the United States. PARTICIPANTS: Catholic sisters (nuns) participating in the Nun Study, a study of aging and Alzheimer's Disease. The 678 participants were 75 to 102 years old (mean 83.3, standard deviation 5.5, median 82.3) at the time of the first functional assessment. Second assessments were obtained an average of 1.6 years later on 575 survivors. MEASUREMENTS: The outcome variables were MMSE scores at the first assessment (Time-one), and MMSE scores at the second assessment (Time-two). The independent variables were age at Time-one, and education (bachelor's degree or no bachelor's degree). RESULTS: Time-one MMSE scores decreased with age at Time-one. The decrease in MMSE scores with age was less in sisters with bachelor's degrees than in sisters without bachelor's degrees. The changes in MMSE scores had a "U-shaped" relationship with Time-one score, where the greatest declines occurred in sisters with intermediate Time-one scores. Stratified analysis by age, education, and Time-one MMSE scores of 20 or greater because of the small numbers of sisters with Time-one scores less than 20. In sisters with Time-one MMSE scores in the categories 20 to 23, 24 to 26, or 27 to 30, older ages at Time-one were associated with greater decline in those with bachelor's degrees, but not in those without bachelor's degrees. Also, lower education was associated with greater decline in sisters aged 75 to 84 years at Time-one, but this education effect disappeared or reversed in sisters who were 85 years of age or older at Time-one. CONCLUSIONS: Cognitive function as measured by the MMSE decreased with age at Time-one, most steeply as a function of age in those without bachelor's degrees. Cognitive function declined over 1.6 years within individuals, and the extent of decline increased with age in the sisters with bachelor's degrees. The extent of decline varied with age and education in an interactive manner, which may have been attributable to a hardy survivor effect in lower educated sisters. It may be necessary to consider such interactions whenever changes in function are studied, particularly when analyses are stratified by the initial level of function.

Aged↗
PubMed1993

Psychopathology associated with Alzheimer's disease and related disorders.

BACKGROUND: This study compared the occurrence of psychiatric symptoms in a large group of community-residing participants enrolled in an Alzheimer's disease patient registry who met clinical diagnostic criteria for Alzheimer's disease or multi-infarct dementia, as well as mixed Alzheimer's disease and multi-infarct dementia. METHODS: Psychiatric morbidity observed from a psychiatric examination of 514 patients with Alzheimer's disease, 135 patients with multi-infarct dementia, and 86 cases with mixed dementia was analyzed using analysis of variance comparing symptoms across groups and chi-square test for differences in frequency of occurrence. Associations between pairs of symptoms were also reported. RESULTS: The frequency of occurrence and patterns of psychiatric problems were similar in patients with Alzheimer's disease and multi-infarct dementia. Agitation was the most frequent symptom, followed by depression, apathy, and behavioral disorders. Patients with mixed dementia had significantly more psychopathology. CONCLUSION: This study demonstrated that significant psychopathology occurs in individuals with Alzheimer's disease or multi-infarct dementia. The high levels of symptoms in mixed dementia suggest that the two conditions have a synergistic effect on behavioral problems. The prevalence of multiple symptoms is higher than previously reported.

Aged↗
PubMed1993

Sex differences in the psychiatric manifestations of Alzheimer's disease.

OBJECTIVE: To test the null hypothesis, ie, that there are no gender differences in psychiatric problems manifest in patients with Alzheimer's disease. DESIGN: Survey. SETTING: Patients living in the community and evaluated at Alzheimer's disease and geriatric outpatient programs. PATIENTS: Three hundred twenty-eight women and 186 men clinically diagnosed with Alzheimer's disease using NINCDS/ADRDA or DSM-III-R criteria. MEASUREMENTS: Psychiatric signs and symptoms recorded following a psychiatric interview, including the Hamilton Depression Rating Scale. RESULTS: Approximately two-thirds of both men and women had psychiatric problems, but women had significantly more multiple symptoms. When pairs of symptoms were analyzed for independence, agitation was only significantly associated with paranoia in men, whereas in women agitation was significantly associated with most other psychiatric problems. CONCLUSION: The higher prevalence of multiple psychiatric problems in women may be due to many factors, including sociodemographic influences, physician bias, and/or other differences between men and women. The finding of a different pattern of association of symptoms with agitation in men and women deserves replication.

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PubMed1993

Drug use patterns of persons with Alzheimer's disease and related disorders living in the community.

OBJECTIVE: To describe drug use patterns by persons with Alzheimer's disease, multi-infarct dementia, and mixed Alzheimer's disease and multi-infarct dementia. DESIGN: Multicenter, patient registry. SETTING: Community-living persons evaluated in primary care, geriatric, and Alzheimer ambulatory settings. PARTICIPANTS: Of the 930 persons in three diagnostic categories, there were 671 with probable or possible Alzheimer's disease by NINCDS/ADRDA criteria or Alzheimer's disease by DSM-III-R criteria, 162 multi-infarct cases by DSM-III-R criteria, and 97 mixed cases by DSM-III-R criteria. In each diagnostic category, 65% were women, and the majority were 70 years or older. MEASUREMENTS: The average number of all prescription and non-prescription drugs and selected therapeutic categories by age, sex, diagnosis, and mini-mental status score at the time of diagnosis or evaluation. RESULTS: Alzheimer patients average 2.3 drugs compared with multi-infarct (4.3; P < 0.0001) and mixed (3.7; P = 0.002) patients, and their pattern of drug use was different when stratified by therapeutic categories and drug classes. Drug use increased with age, and women used significantly more drugs than men in all three diagnostic categories. Women with Alzheimer's disease used significantly more cardiovascular drugs than men with Alzheimer's disease (P < 0.05). The lower the mini-mental status score in patients with any dementia, the greater the mean number of central nervous system agents used. The higher the mini-mental status score in a patient with multi-infarct or mixed dementia, the greater the use of cardiovascular drugs. CONCLUSION: Drug use by Alzheimer patients was lower than in multi-infarct and mixed patients, primarily due to a lower prevalence of cardiovascular drugs.

Age Factors↗
PubMed1992

Human serum stimulates Alzheimer markers in cultured hippocampal neurons.

The mechanism for promoting the distinct types of lesions in the Alzheimer disease (AD) brain and other changes outside the brain is unknown. We examined neurons in culture, unprotected by glia or a blood-brain barrier, to determine if exposure to serum from Alzheimer patients would affect markers for Alzheimer brain lesions. Rat hippocampal neurons were first grown for 4 days in a new serum-free culture medium, then exposed for 24 hr to human sera. Sera from 12 AD patients or their spouses increased four molecular markers characteristic of Alzheimer senile plaques and neurofibrillary tangles: Alz-50, beta-amyloid (beta/A4), MAP2, and ubiquitin, each with their expected cytologic distributions. Sera from ten young adults produced significantly less stimulation. By quantitative immunofluorescence, neuronal exposure to the elderly human sera produced 1.8- to 2.5-fold increases in mean fluorescent area/cell for each of these four markers relative to no serum exposure. As controls, an unrelated neuronal marker, enolase, was unaffected and fetal bovine serum did not stimulate immunoreactivity. Neuron viability and somal area were unaffected at 24 hours. The MAP2 increases were dose dependent with negligible effect at 2% serum and maximum effect at 10% serum after 24 hr. The MAP2 increase was greater after 48 hr of exposure than 24 hr and negligible at 2 hr. This stimulation of AD markers by human serum suggests that the genesis of both neuronal plaques and tangles may arise from access of toxic serum factors to susceptible neurons and/or failure to detoxify these factors.

Adult↗
PubMed1992

Assessing Alzheimer severity with a global clinical scale.

Diagnosis of dementia needs to be complemented by precise determination of disease severity across the broad spectrum of disease progression. The Mini-Mental State Exam (MMS), the Activities-of-Daily-Living assessment (ADL) and the Clinical Dementia Rating scale (CDR) were modified for direct comparability and administered to 112 outpatients and 45 nursing home residents with a range of dementia severity from mild to profound. The scales showed the highest correlations for the probable Alzheimer's disease patient group (62) (Global Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment; EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86). For these patients, scores on the individual scales tended to be similar. Disparity among the three scores for individual cases was associated with the presence of comorbidities. The high correlations and correspondence among these scales demonstrate their reliability, validity, and utility in the assessment of dementia severity. The use of an average of these measures, with their increased precision, may give a more accurate indication of dementia severity over a broader range of impairment.

Activities of Daily Living↗
PubMed1992

Functional status and clinical findings in patients with Alzheimer's disease.

We analyzed the association of clinical findings with impaired functional status, i.e., activities of daily living (ADLs), in a sample of 240 patients diagnosed with Alzheimer's disease by NINCDS/ADRDA or DSM-III-R criteria. Logistic regression models were used to determine independent predictors of both the number of ADL impairments and number of ADL impairments characterized as moderate to severe. Two psychiatric problems, behavioral disorders and apathy, as well as a history of hypertension were significantly associated with ADL impairment independent of age, sex, race, and cognitive impairment. Behavioral disorders and apathy were also significantly associated with moderate to severe ADL impairment, but hypertension was not significant at this level.

Activities of Daily Living↗
PubMed1992

Severe family violence and Alzheimer's disease: prevalence and risk factors.

This study describes the prevalence of violence and the putative risk factors for violence in 184 Alzheimer patients and their primary caregivers living in the community. Analysis of the severe violence subscale of the Conflict Tactics Scale indicated that 15.8% of patients had been violent in the year since diagnosis. A total of 5.4% of caregivers reported being violent toward the patient. The overall prevalence of violence was 17.4%. The variables most associated with violence were caregiver depression and living arrangement.

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