Biomedical subjects

Warren W Barker

Publications and source records attributed to Warren W Barker.

12 recordsLinked to original sources

PubMed2006

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies.

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.

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PubMed2006

Using different memory cutoffs to assess mild cognitive impairment.

OBJECTIVE: Although mild cognitive impairment (MCI) is characterized by performance on memory and other measures below expected normative values, neither a scientific rationale nor a consensus exists regarding which measures have the most use or the optimal cutoffs to use to establish impairment. METHODS: Different memory measures were administered to 80 normal community-dwelling subjects divided into two age groups. This provided conormed data on eight different memory indices by which to compare 23 nondemented clinically diagnosed patients with MCI who met all other criteria for Alzheimer disease (AD). RESULTS: On immediate memory for passages, delayed visual reproduction, object memory, and a measure sensitive to semantic interference, 70%-78% of patients with MCI were identified as impaired at 1.5 standard deviations or greater below expected levels. Conditional logistical regression for age-matched samples indicated that consideration of raw scores for these neuropsychologic tests in combination did not significantly change the odds of MCI diagnosis. When impairment relative to the total normal elderly sample was calculated based on one or more impairments at a 1.5 or greater cutoff, specificity fell below acceptable levels when more than three memory measures were considered. CONCLUSION: An array of widely used neuropsychologic measures demonstrated utility in distinguishing patients with MCI-AD from cognitively normal community-dwelling elders. The appropriateness of more or less stringent cutoffs was highly influenced by the number of measures considered. These findings have important implications regarding the choice of cut points for impairment used for the diagnosis of MCI in both research and clinical settings.

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PubMed2005

The cyclooxygenase 2 -765 C promoter allele is a protective factor for Alzheimer's disease.

The cyclooxygenase-2 enzyme (COX-2) is of particular importance in the inflammatory response and recent findings have demonstrated a considerable role in Alzheimer's disease (AD) pathogenesis. In order to assess the possible putative role of a COX-2 polymorphism (765G/C) in AD, we examined its distribution in 161 community-based controls and 168 AD clinic-based cases previously recruited from memory disorder clinics in Tampa and Miami, Florida. There were no significant differences between the two groups in age/age of onset or gender. A significant difference was observed in the distribution of the COX-2 -765 alleles between AD cases and controls (chi(2) = 6.565, p = .010; OR = .596; CI = [.401-.888], p = .011), with the frequency of the C allele being higher in controls. In addition, a significant difference was observed for this polymorphism by genotype (chi(2) = 6.561, p = .038) and by presence or absence of C+ genotypes (chi(2) = 6.207, p = .013; OR = .464, CI = [.351-.885], p = .013). In this sample, the C allele of COX-2 -765 promoter polymorphism is associated with decreased risk of Alzheimer's disease, a finding which further supports the involvement of COX-2 in AD etiology.

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PubMed2005

A clinical perspective of mild cognitive impairment: what radiologists should know.

Mild cognitive impairment (MCI), a major risk factor for dementia, has an amnestic subtype that has a high probability of progressing to Alzheimer's disease. The rate of progression may be predicted by the severity of memory impairment at baseline, the severity of hippocampal atrophy, and, possibly, the presence of an epsilon4 allele of the apolipoprotein E gene. MCI can be diagnosed using purely clinical or a combination of clinical and neuropsychologic criteria. Treatment trials show no disease-modifying effect. The radiologists' role is to determine whether or not the hallmarks of degenerative and vascular disease of the brain are present, aiding in the diagnosis of the cause of MCI.

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PubMed2004

Conversion to dementia among two groups with cognitive impairment. A preliminary report.

OBJECTIVE: To determine the conversion rates to dementia in patients diagnosed with mild cognitive impairment (MCI) thought to be caused by incipient Alzheimer's disease (MCI-AD) or with MCI with features of vascular disease (MCI-Vas). METHODS: On the basis of patient history, neurocognitive, neurological and MRI evaluation, 99 patients were diagnosed with MCI-AD and 35 with MCI-Vas. Conversion to dementia over an average of a 2.4 +/- 1.8-year period was determined. RESULTS: Over the follow-up period, 44% converted to dementia, 51.5% remained classified as MCI, and 4.5% were reclassified as cognitively normal. The conversion rate to dementia was significantly faster at 3 years for the MCI-AD (50.5%) than for the MCI-Vas group (25.7%). The neuropsychological test found to best differentiate converters from non-converters was the Fuld-OME, a measure of learning and recall. Age, education, gender or APOE epsilon4 allele frequency did not differentiate converters from non-converters. CONCLUSIONS: MCI-AD and MCI-Vas are clinically meaningful subtypes of MCI that may convert to dementia at different rates. Prospective studies on larger subsets of MCI patients are required to confirm these findings.

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PubMed2004

No association between subjective memory complaints and apolipoprotein E genotype in cognitively intact elderly.

OBJECTIVE: This cross-sectional study examined the relationship between subjective memory complaints and the apolipoprotein epsilon 4 allele (epsilon4), a genetic risk factor for Alzheimer's disease (AD), among cognitively normal subjects identified from a community memory screening. DESIGN: The sample comprised 232 consecutive white non-Hispanic older adults who presented to a free community-based memory-screening program at a University affiliated memory disorders center. Participants were classified as cognitively normal based on scores on the age and educated adjusted Folstein Mini-Mental Status Exam (MMSAdj) and a brief Delayed Verbal Recall Test (DRT). Subjects were assessed for APOE genotype, subjective memory complaints (Memory Questionnaire, MQ), depressive symptoms (Hamilton Depression Rating Scale, HDRS), and history of four major medical conditions that have been associated with memory loss (stroke/transient ischemic attack [TIA], atherosclerotic heart disease, hypertension, and diabetes). A hierarchical regression analysis was performed to examine the association between APOE genotype and memory complaints after controlling for a host of potential confounding factors. RESULTS: The APOE epsilon4 allele frequency for cognitively normal subjects was 0.13. Subjective memory complaints were predicted by depressive symptoms and a history of stroke/TIA. They were not associated with APOE genotype, MMSAdj score, DRT score, age, education, gender, and reported history of atherosclerotic heart disease, hypertension, or diabetes. CONCLUSION: The results did not suggest an association between subjective memory complaints and the APOE epsilon4 allele in this sample of cognitively intact subjects. This indicates that memory complaints may confer risk for future dementia through pathways independent of APOE genotype. The results also show that older adults with memory complaints are at increased risk for underlying depression.

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PubMed2004

Apolipoprotein E polymorphism and age of onset for Alzheimer's disease in a bi-ethnic sample.

OBJECTIVE: This study examined the association between the Apolipoprotein-E epsilon4 allele (APOE epsilon4) and age of disease onset in a bi-ethnic sample of community dwelling Alzheimer's disease (AD) patients. DESIGN: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic. SUBJECTS: A clinic-based cohort of white non-Hispanic (WNH; n=601) and white Hispanic (WH; n = 359) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria. MEASURES: Global cognitive functioning of the subjects was evaluated using the Mini-mental State Exam. The age of onset of AD was calculated from the patient's current age minus the reported duration of disease obtained from a knowledgeable family member. RESULTS: A significant relationship was discovered between APOE epsilon4 and age of onset for WNH, with lower ages of onset among patients carrying the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes in relation to patients with the epsilon3/epsilon3 genotype. The results revealed a more modest effect for APOE genotype in the WH cohort, with a lower age of onset witnessed among epsilon4 positive patients (epsilon2/epsilon4, epsilon3/epsilon4 and epsilon4/epsilon4 genotypes) in comparison to epsilon4 negative patients (epsilon2/epsilon2, epsilon2/epsilon3 and epsilon3/epsilon3 genotypes). CONCLUSION: The association between the epsilon4 allele and earlier age of onset was more pronounced in WNH compared to WH patients, suggesting the impact of APOE polymorphism on clinical phenotype may be different for distinct ethnic groups in the U.S.

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PubMed2004

Semantic interference deficits and the detection of mild Alzheimer's disease and mild cognitive impairment without dementia.

Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer's disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation.

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PubMed2002

Apolipoprotein E genotype and cognitive impairment in community-dwelling black older adults.

OBJECTIVE: The relationship between the epsilon 4 allele of the apolipoprotein E gene (APOE-epsilon4) located on chromosome 19 and Alzheimer's disease is well documented among Caucasian populations. However, the findings of research addressing the link between APOE polymorphism and neurocognitive functioning in populations of African origin from around the world have been equivocal. Therefore, the current study explored the relation of APOE-epsilon4 with cognitive impairment in a sample of community-dwelling English-speaking elderly blacks. METHODS: All participants (N = 57) were recruited consecutively from a community memory-screening program at a University affiliated Memory Disorders Clinic and evaluated using standardized assessment procedures. Cognitive impairment was classified according to an age and education adjusted Mini-Mental State Exam score of less than 24 as well as poorer functioning on a measure of delayed verbal memory. RESULTS: Increased risk for global cognitive dysfunction (OR = 9.5, 95 percent CI = 2.3-55.3, p = .004) and poorer verbal recall performance (beta = -.36, p = .006) were linked with the APOE epsilon4 allele after controlling for the potentially confounding effects of age, education, and gender. CONCLUSIONS: This investigation supports the role of APOE polymorphism in determining neurocognitive impairment among black elders residing in the community.

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PubMedDate not supplied

Apolipoprotein E polymorphism and cognitive impairment in a bi-ethnic community-dwelling elderly sample.

The epsilon 4 (epsilon 4) and epsilon 2 (epsilon 2) alleles of the apolipoprotein gene (APOE) located on chromosome 19 have been associated with increased and decreased risk for Alzheimer disease (AD) in older adults, respectively. However, there is a dearth of studies examining the relation of APOE polymorphism with cognitive functioning among community-dwelling ethnic minority elderly. This study examined the risk for cognitive impairment associated with the APOE epsilon 4 and epsilon 2 alleles in a community-based cohort of non-Hispanic white (NHW; N = 739) and white Hispanics (WH; N=321). All patients were recruited consecutively from a memory-screening program and evaluated using standardized assessment procedures. Cognitive impairment was classified according to an age and education adjusted Folstein Mini-Mental State Exam (MMSAdj) score of less than 24. The results indicated the APOE epsilon 4 allele was associated with increased risk for cognitive dysfunction in NHW and WH after controlling for the effects of age, education, and gender. This risk was generally observed to be dose-dependent, with greater risk among epsilon 4 homozygotes in relation to epsilon 4 heterozygotes. The epsilon 2 allele of APOE did not confer decreased risk for cognitive impairment among NHW and WH. This study supports the relation of APOE polymorphism to cognitive dysfunction among two ethnic populations residing in the community.

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PubMedDate not supplied

Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank.

Alzheimer disease (AD) is the most common dementing illness in the elderly, but there is equivocal evidence regarding the frequency of other disorders such as Lewy body disease (LBD), vascular dementia (VaD), frontotemporal dementia (FTD), and hippocampal sclerosis (HS). This ambiguity may be related to factors such as the age and gender of subjects with dementia. Therefore, the objective of this study was to calculate the relative frequencies of AD, LBD, VaD, FTD, and HS among 382 subjects with dementia from the State of Florida Brain Bank and to study the effect of age and gender on these frequencies. AD was the most frequent pathologic finding (77%), followed by LBD (26%), VaD (18%), HS (13%), and FTD (5%). Mixed pathology was common: Concomitant AD was present in 66% of LBD patients, 77% of VaD patients, and 66% of HS patients. The relative frequency of VaD increased with age, whereas the relative frequencies of FTD and LBD declined with age. Males were overrepresented among those with LBD, whereas females were overrepresented among AD subjects with onset age over 70 years. These estimates of the a priori probabilities of dementing disorders have implications for clinicians and researchers.

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PubMedDate not supplied

The effect of a memory screening program on the early diagnosis of Alzheimer disease.

CONTEXT: Alzheimer Disease (AD) is often diagnosed at a moderately advanced stage, even though its early detection has become increasingly important, because of the continuing development of treatments that may improve its outcome. OBJECTIVE: To determine if a free memory screening program is associated with an earlier diagnosis of AD, compared with traditional referral methods, such as by physicians and family members. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 1489 consecutive patients with AD who presented to an outpatient memory disorders clinic between 1993 and 2002. Subjects were classified according to referral source (memory screening, physician, family/friend, other), and self-reported ethnicity (white non-Hispanic, white Hispanic). The associations between referral source and the presenting cognitive and behavioral status of subjects were evaluated using analysis of variance and logistic regression analyses, after controlling for potentially confounding factors. MAIN OUTCOME MEASURES: Score on the Folstein Mini-Mental State Examination (MMSE), duration of cognitive symptoms, and presence of psychosis, defined as delusions and/or hallucinations. RESULTS: After controlling for ethnicity, gender, and the year of diagnosis, subjects with AD, who were referred by the memory screening program, scored significantly higher at presentation on the MMSE (20.8 +/- 5.7), than those referred by physicians (18.8 +/- 6.6), family/friends (16.8 +/- 6.6), or other referral sources (15.3 +/- 7.1). Subjects with AD, referred by the memory screening program, also had a lower reported duration of illness at presentation, and a decreased frequency of psychosis compared with those referred by family/friend and other methods. Other factors related to a diagnosis of AD at a later stage included female gender, Hispanic ethnicity, and a diagnosis early in the 1993 to 2002 time period. CONCLUSIONS: The memory screening program referred patients with AD to a memory clinic at an earlier phase of illness compared with traditional methods such as physician referral.

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