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Biomedical subjects

F A Schmitt

Publications and source records attributed to F A Schmitt.

At least 19 recordsLinked to original sources
PubMed2006

Risk factors for transitions from normal to mild cognitive impairment and dementia.

OBJECTIVE: To identify risk factors associated with transitions from cognitively normal to various forms of mild cognitive impairment (MCI) and then from MCI into early dementia with death as a competing state. METHODS: Cognitive assessments from 554 subjects participating in a longitudinal study at the University of Kentucky AD Center were used to classify individuals into one of three transient states at any visit: cognitively normal, amnestic MCI, or mixed MCI. Between visits subjects could die or become demented. A series of polytomous logistic models were used to model transitions among these states over time and to determine how the log odds of these transitions vary with age, education, sex, family history of dementia, and APOE status. RESULTS: Age affects all transitions among transient states as well as those to dementia or death. Presence of at least one apolipoprotein 4 allele affects transitions from cognitively normal into amnestic MCI or into dementia. At most 12 years of education affects transitions into mixed MCI. Transitions do not vary with sex or family history. CONCLUSION: Aside from age, the usual risk factors associated with conversion from cognitively normal into dementia are likely risk factors for transitions into mild cognitive impairment.

Aged↗
PubMed2005

Evidence of increased oxidative damage in subjects with mild cognitive impairment.

OBJECTIVE: To determine if increased levels of oxidative damage are present in the brains of persons with mild cognitive impairment (MCI), a condition that often precedes Alzheimer disease (AD). METHODS: The authors assessed the amount of protein carbonyls, thiobarbituric acid-reactive substances (TBARS), and malondialdehyde in the superior and middle temporal gyri (SMTG) and cerebellum of short postmortem interval and longitudinally evaluated normal subjects and those with MCI and early AD. RESULTS: Elevated levels of protein carbonyls (approximately 25%), malondialdehyde (approximately 60%), and TBARS (approximately 210%) were observed in the SMTG of individuals with MCI and early AD vs normal control subjects. The elevation in TBARS was associated with the numbers of neuritic but not diffuse plaques. Levels of protein carbonyls increased as delayed verbal memory performance declined. CONCLUSION: Oxidative damage occurs in the brain of subjects with mild cognitive impairment, suggesting that oxidative damage may be one of the earliest events in the onset and progression of Alzheimer disease.

Aged↗
PubMed2005

Longitudinal functional alterations in asymptomatic women at risk for Alzheimer's disease.

PURPOSE: The authors sought to determine whether known alterations of brain function in normal individuals who are at high risk for Alzheimer's disease (AD) worsen or stay the same after a significant interval of time. METHODS: The authors used functional magnetic resonance imaging (fMRI) to observe cortical activation during confrontation naming in 14 women with high AD risk and 10 with low risk, based on family history and apolipoprotein-E4 allele status. They repeated the identical scan protocol in the same patients after 4 years. RESULTS: fMRI activation in high-AD-risk participants was found to be further diverged from that of their low-AD-risk counterparts over this period. CONCLUSION: fMRI may report on the presence and progression of neuropathology in the ventral temporal cortex or in functionally connected regions in presymptomatic AD.

Alzheimer Disease↗
PubMed2002

Women at risk for AD show increased parietal activation during a fluency task.

BACKGROUND: Imaging studies have shown disparities in resting metabolism and in functional activation between cognitively normal individuals at high and low risk for AD. A recent study has shown increased parietal activation in high-risk subjects during a paired associates recall task, which the authors postulated might overlap activation typically observed in verbal fluency. OBJECTIVE: To determine whether parietal activation is altered in a letter fluency task in cognitively normal individuals at high risk for AD. METHODS: fMRI was used to compare cortical activation between two groups of cognitively normal women differing in their risk for developing AD. A letter fluency task was used, which activates left frontal and parietal regions. The risk groups differed in family history of AD and APOE allele status but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 53 years. RESULTS: The regional patterns of brain activation were similar between groups and similar to patterns observed by other investigators. However, the high-risk group showed significantly increased activation in the left parietal region despite identical letter fluency performance between risk groups. CONCLUSIONS: Cognitively normal individuals at high risk for AD show increased brain activation in the left parietal region with letter fluency, a region adjacent to that observed by others using a recall task. This convergence of results indicates disruption of functional circuits involving the left parietal lobe in asymptomatic individuals at increased risk for AD.

Alzheimer Disease↗
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.

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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.

Aged↗
PubMed2001

Acceleration of HIV dementia with methamphetamine and cocaine.

We report a patient with rapidly accelerating HIV dementia accompanied by seizures and an unusual movement disorder despite highly potent antiretroviral therapy. This clinical constellation was associated with the non-parenteral use of methamphetamine and cocaine. Fractional enhancement time on post contrast magnetic resonance imaging studies revealed a progressive breakdown of the blood brain barrier particularly in the basal ganglia. The movement disorder but not the dementia responded to a combination of dopamine replacement and anticholinergic therapy. While the movement disorder may have been unmasked by concomitant anticonvulsant therapy, we suggest in this instance, that prior drug abuse synergized with HIV to cause a domino effect on cerebral function. Careful attention and analysis to histories of remote non-injecting drug abuse may help substantiate our hypothesis.

AIDS Dementia Complex↗
PubMed2001

Brain donation in normal aging: procedures, motivations, and donor characteristics from the Biologically Resilient Adults in Neurological Studies (BRAiNS) Project.

Medical autopsy rates have been declining for the past several decades, yet, for more than a decade, the University of Kentucky Alzheimer's Disease Research Center has been recruiting healthy older adults into a program involving annual assessments of mental status, biannual medical and neurological exams, and prearranged postmortem brain examination. The present article focuses on the characteristics of these donors to explore potential factors that contribute to the decision to donate. The motivations of this unique group of individuals could serve to inform physicians who request autopsies for medical and research purposes. Over 500 volunteers who have enrolled in this program are well-educated community-dwelling adults over the age of 60. They are generally motivated by personal experiences with Alzheimer's disease, referral by someone already enrolled, and a desire to promote scientific knowledge. These volunteers' reasons suggest that rates of tissue donation or autopsy for basic research and investigations of causes of death might be increased by providing individuals and families with information concerning the medical and scientific value of the procedure. Within research settings, encouraging participant recruitment of friends or family members would likely increase tissue acquisition rates.

Aged↗
PubMed2001

Differences in functional magnetic resonance imaging activation by category in a visual confrontation naming task.

OBJECTIVE: Cortical processing involved in seemingly similar tasks may differ in important ways. The authors mapped cortical regions engaged in a commonly performed picture naming task, seeking differences by semantic category. Functional magnetic resonance imaging was used during presentation of standardized line drawings in 18 healthy right-handed female participants, comparing living versus nonliving entities. During visual naming, across categories there was strong activation of left frontal (BA45/47), bilateral temporo-occipital junction (BA19), and inferior temporal regions (BA36/37). Activation of right inferior temporal cortex (BA19 and BA37) was greater during naming of living versus nonliving category items. No category differences in activation strength in the left temporal lobe were observed. The authors conclude that visual semantic operations may involve visual association cortex in the right temporal lobe in women.

Brain Mapping↗
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.

Aged↗
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.

Aged↗
PubMed1999

Altered brain activation in cognitively intact individuals at high risk for Alzheimer's disease.

OBJECTIVE: To determine whether brain function is altered in cognitively normal individuals at high risk for AD several years before the typical age at onset for this illness. BACKGROUND: Neuropathologic alterations in AD precede cognitive impairment by several years. It is unknown whether functional alterations in neural circuitry accompany these neuropathologic changes, and if so, whether they may be detectable before onset of symptoms. METHODS: We used functional MRI to compare cortical activation between two groups of cognitively normal women differing only in their risk for developing AD. Visual naming and letter fluency tasks were used to activate brain areas subserving object and face recognition, previously described sites of hypometabolism and neuropathologic alteration in AD. The risk groups differed in family history of AD and apolipoprotein E allele status, but were matched in age, education, and measures of cognitive performance. Average age of the study participants was 52 years. RESULTS: The regional patterns of brain activation were similar between groups. However, the high risk group showed areas of significantly reduced activation in the mid- and posterior inferotemporal regions bilaterally during both tasks despite identical naming and letter fluency performance. CONCLUSIONS: Cognitively normal individuals at high risk for AD demonstrate decreased brain activation in key areas engaged during naming and fluency tasks. Decreased activation in the high risk group may be a consequence of the presence of subclinical neuropathology in the inferotemporal region or in the inputs to that region. If so, these findings provide evidence of a window of opportunity for disease-modifying treatment before the onset of symptomatic AD.

Adult↗
PubMed1999

Critical decline in fine motor hand movements in human aging.

BACKGROUND: Slowing of motor movements in human aging is a well-known occurrence, but its biologic basis is poorly understood. Reliable quantitation may refine observations of this phenomenon to better aid research on this entity. METHODS: A panel equipped with timing sensors under computer control was used to measure upper extremity movement times in two groups of healthy individuals: adults younger than 60 years of age (n = 56; range, 18-58 years) and adults older than 60 years of age (n = 38; range, 61-94 years). RESULTS: Fine motor performance was better in the dominant hand (p = 0.0007) regardless of age. Adult and aged groups differed on two basic timing measures, which reflect coarse motor and fine motor performance (p < 0.0001). There were no gender differences on either measure. There was a strong effect of task difficulty with age on coarse motor (p < 0.01) and fine motor (p < 0.0001) measures. The fine motor measure of hand performance in healthy individuals correlated in a nonlinear fashion with age for more difficult tasks (r2 = 0.63) but showed a simple linear relation for less-demanding tasks (r2 = 0.5). CONCLUSION: This technique sensitively detects age-related motor performance decline in humans. There may be a critical period in late midlife when fine motor performance decline either begins or abruptly worsens.

Adolescent↗
PubMed1999

Alzheimer neuropathologic alterations in aged cognitively normal subjects.

The histopathologic changes distinguishing early Alzheimer disease (AD) from normal or pathologic aging are not clearly defined. This report describes the autopsy findings of 59 elderly, well-educated, volunteers. They were examined longitudinally with mental status testing, some for up to 8 years, as part of our normal aging study. This study reveals that (1) the brains of many subjects who did not show cognitive impairment on neuropsychologic testing contain abundant senile plaques (SP) and/or neurofibrillary tangles (NFT); (2) 29 subjects met Khachaturian criteria for AD, 15 met CERAD and 7 met National Institute on Aging-Reagan Institute guidelines; (3) Braak and Braak staging method included 9 in stage IV subjects, 4 in stage V, and 1 in stage VI; (4) there was a progression of NFT from entorhinal cortex to hippocampus and amygdala as a function of age; (5) 2 subjects met criteria for a diagnosis of dementia with Lewy bodies but were not demented; (6) cerebral amyloid angiopathy was present in leptomeningeal vessels in 75% of subjects and in parenchymal vessels in 62% of subjects; (7) only 10 of 59 subjects (17%) had no or few degenerative brain changes. Our study demonstrates that the brains of a large percentage of cognitively normal, relatively well-educated individuals contain numerous degenerative changes and only a small percentage are relatively free of these changes.

Aged↗
PubMed1999

MRI temporal lobe volume measures and neuropsychologic function in Alzheimer's disease.

The authors performed quantitation of the temporal lobes using magnetic resonance imaging in 20 patients with mild-to-moderate Alzheimer's disease, 20 age-matched aged control subjects, and 26 healthy young volunteers. Compared to young subjects, aged controls showed volume reductions in amygdala (17%, p = 0.02), hippocampus (15%, p = 0.0001) and temporal lobe (22%, p = 0.0001). Compared to aged controls, Alzheimer's subjects showed further volume reductions in amygdala (33%, p = 0.0001) and hippocampus (20%, p = 0.006) but not temporal lobe (7%, p = 0.15). In Alzheimer's subjects, left temporal lobe volume correlated strongly with the Mini Mental State (MMSE) score (adjusted r2 = 0.46, p = 0.0006) whereas right amygdala volume correlated inversely with the noncognitive ADAS score (adjusted r2 = 0.46, p = 0.0006). The authors conclude that significant volume changes occur in the temporal lobe in aging and in Alzheimer's disease, with the greatest percentage reductions in the amygdala in Alzheimer's disease. Temporal neocortical atrophy and temporal limbic atrophy might be associated with different patterns of performance and behavior in Alzheimer's patients.

Adult↗
PubMed1999

Short-term neuropsychological outcome following Gamma Knife radiosurgery for arteriovenous malformations: a preliminary report.

This study investigated the effect of Gamma Knife radiosurgery for the treatment of arteriovenous malformations (AVMs) on neuropsychological functioning. We examined neuropsychological performance in 10 patients before and after radiosurgical treatment with the Leksell cobalt-60 Gamma Knife unit. The patients included 7 right-handed women and 3 right-handed men. Three patients had left hemisphere AVMs, 4 had right hemisphere AVMs, and 3 had midline AVMs. Each patient was given neuropsychological testing within 1 week before Gamma Knife radiosurgery. Testing was repeated an average of 11.4 months after treatment. There were no statistically significant differences between pre- and postradiosurgical neuropsychological test scores on any measure. Pretreatment AVM diameter as measured on magnetic resonance scans ranged from 1.6 to 6.5 cm. After treatment, 2 AVMs disappeared, 4 decreased slightly in size, and 4 remained unchanged. We conclude that Gamma Knife radiotherapy in this sample of patients was neither detrimental nor beneficial to neuropsychological functioning.

Adult↗