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ABSTRACT: OBJECTIVE: To determine whether the temporal onset of visual phenomena distinguishes Lewy body disease (LBD) from Alzheimer's disease (AD), and to characterize the extent Lewy bodies and neurofibrillary tangles are associated with these clinical features. METHODS: Consecutive cases of autopsy-confirmed LBD (n = 41), AD (n = 70), and AD with amygdala-predominant Lewy bodies (AD-ALB) (n = 14) with a documented clinical history of dementia were included. We mailed questionnaires to next-of-kin asking about symptoms during life. Lewy pathology and neurofibrillary tangle pathology were assessed. RESULTS: The occurrence of visual hallucinations, misperceptions and family misidentification did not distinguish LBD from AD or AD-ALB, but the onset was earlier in LBD compared to AD and AD-ALB. When visual hallucinations developed within the first 5 years of dementia, the odds were 4-5 times greater for autopsy-confirmed LBD (or intermediate/high likelihood dementia with Lewy bodies) and not AD or AD-ALB. In LBD, limbic but not cortical Lewy body pathology was related to an earlier onset of visual hallucinations, while limbic and cortical Lewy body pathology were associated with visual misperceptions and misidentification. Cortical neurofibrillary tangle burden was associated with an earlier onset of misidentification and misperceptions in LBD and AD, but only with earlier visual hallucinations in AD/AD-ALB. CONCLUSION: When visual hallucinations occur within the first 5 years of the dementia, a diagnosis of LBD was more likely than AD. Visual hallucinations in LBD were associated with limbic Lewy body pathology. Visual misperceptions and misidentification delusions were related to cortical Lewy body and neurofibrillary tangle burden in LBD and AD/AD-ALB.
Parkinsonism & Related Disorders 11/2012; · 3.80 Impact Factor
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R Duara,
D A Loewenstein,
E Potter,
J Appel,
M T Greig,
R Urs,
Q Shen,
A Raj,
B Small, W Barker,
E Schofield,
Y Wu,
H Potter
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ABSTRACT: Despite convenience, accessibility, and strong correlation to severity of Alzheimer disease (AD) pathology, medial temporal lobe atrophy (MTA) has not been used as a criterion in the diagnosis of prodromal and probable AD.
Using a newly validated visual rating system, mean MTA scores of three bilateral medial temporal lobe structures were compared for subjects with no cognitive impairment (NCI) (n = 117), nonamnestic mild cognitive impairment (MCI) (n = 46), amnestic MCI (n = 45), and probable AD (n = 53). Correlations between MTA scores and neuropsychological test scores at baseline, and predictors of change in diagnosis at 1-year follow-up were evaluated.
With NCI as the reference group, a mean MTA cut score of 1.33 yielded an optimal sensitivity/specificity of 85%/82% for probable AD subjects and 80%/82% for amnestic MCI subjects. MTA and Clinical Dementia Rating Sum of Boxes scores at baseline were independent and additive predictors of diagnosis at baseline, and of transition from NCI to MCI or from MCI to dementia at 1-year follow-up.
Medial temporal lobe atrophy (MTA) scores 1) distinguish probable Alzheimer disease (AD) and amnestic mild cognitive impairment (MCI) subjects from nonamnestic MCI and no cognitive impairment (NCI) subjects, 2) help predict diagnosis at baseline, and 3) predict transition from NCI to MCI and from MCI to probable AD. MTA scores should be used as a criterion in the clinical diagnosis of AD.
Neurology 01/2009; 71(24):1986-92. · 8.31 Impact Factor
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B K Woodruff,
N R Graff-Radford,
T J Ferman,
D W Dickson,
M W DeLucia,
J E Crook,
Z Arvanitakis,
S Brassler,
C Waters, W Barker,
R Duara
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ABSTRACT: Genetic factors are important in Alzheimer disease (AD) and Parkinson disease but have not been well characterized in Lewy body dementia (LBD). The authors obtained family history in patients from an autopsy series of AD and LBD and in living healthy controls. A family history of dementia was more common in both LBD and AD compared with controls, suggesting that genetic factors are as important in LBD as they are in AD.
Neurology 07/2006; 66(12):1949-50. · 8.31 Impact Factor
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ABSTRACT: The authors assessed the equivalence of the factor structure of the Cornell Scale for Depression in Dementia (CSDD) in samples of Anglo and Hispanic patients with Alzheimer's disease (AD). Comparing the factor structure of the CSDD in these groups helps establish its validity and aids in its clinical interpretation with Hispanic patients. CSDD ratings were first subjected to preliminary exploratory factor analyses; then the factor structure of the CSDD across groups of English- and Spanish-speaking patients was tested using structural equation modeling. Analyses showed overall similarity in the CSDD factor structure for the two groups but also revealed differences in factor content for several items. The authors discuss the relevance of these differences for those using the CSDD with Hispanic AD patients.
American Journal of Geriatric Psychiatry 02/2001; 9(3):217-24. · 3.64 Impact Factor
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ABSTRACT: This report addresses the clinical differentiation of Alzheimer's disease (AD) from frontotemporal dementia (FTD), including Pick's disease. The accuracy of a clinical diagnosis of a dementing disorder is determined in part by the prior probability (base rates) of the disorder, which predicts an overwhelming likelihood of a diagnosis of AD, because the prevalence of AD is much greater than FTD. The clinical features of the disorder also determine the accuracy of diagnosis. Recent studies have reported an improvement in the differential diagnosis of FTD, utilizing the Lund-Manchester criteria. Patients with FTD typically have early noncognitive behavioral changes with relatively spared cognition, frontal atrophy and enlargement of the Sylvian fissures on CT and MRI scans, and frontal-temporal deficits on SPECT or PET scans. In contrast, AD patients have early cognitive changes with relatively preserved personality and behavior, hippocampal and medial-temporal lobe atrophy on CT or MRI scans, and parietotemporal SPECT or PET deficits.
Dementia and Geriatric Cognitive Disorders 02/1999; 10 Suppl 1:37-42. · 2.14 Impact Factor
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JAMA The Journal of the American Medical Association 12/1998; 280(19):1661-2; author reply 1663. · 30.03 Impact Factor
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ABSTRACT: The epsilon4 allele of the apolipoprotein E gene (APOE) has repeatedly been associated with increased risk for Alzheimer's disease (AD). Bullido and colleagues recently identified a polymorphism in the promoter region of the APOE gene (-491A/T) and found that -491A homozygosity predicted AD independently of APOE epsilon4. Since the -491A/T polymorphism and the known APOE polymorphism must be in tight linkage disequilibrium, and the later polymorphism is know to be associated with the disease, we wished to determine to what extent this linkage disequilibrium explained the -491A/T polymorphism association with Alzheimer's disease. We genotyped a community-based control sample (n = 132) and a clinic-based Alzheimer's disease sample (n = 190) for the known APOE and -491A/T polymorphisms, and find that, while the -491A/T polymorphism confers some independent risk for AD, linkage disequilibrium between the known APOE and -491A/T polymorphic sites explains most of the -491A association. Furthermore, when considering the known APOE and -491A/T polymorphisms alone, APOE epsilon4 status is the best predictor of the disease.
Neuroscience Letters 09/1998; 252(2):95-8. · 2.11 Impact Factor
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Y Q Song,
E Rogaeva,
S Premkumar,
N Brindle,
T Kawarai,
A Orlacchio,
G Yu,
G Levesque,
M Nishimura,
M Ikeda,
Y Pei,
C O'Toole,
R Duara, W Barker,
S Sorbi,
M Freedman,
L Farrer,
P St George-Hyslop
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ABSTRACT: A novel polymorphism (-491 A/T) within the regulatory region on the apolipoprotein E gene has recently been reported to be associated with risk for Alzheimer disease (AD). To test this association in an independent data set, we have examined this polymorphism in a sample of 88 well-characterized AD cases and compared the allele frequency and genotype frequencies for this polymorphism with those observed in 112 cognitively normal subjects drawn from the same ethnic group. These results suggest that in the current data set at least, the -491 A/T polymorphism is not associated with risk for AD, but may be in partial linkage disequilibrium with the APOE epsilon2/epsilon3/epsilon4 polymorphism.
Neuroscience Letters 08/1998; 250(3):189-92. · 2.11 Impact Factor
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ABSTRACT: It is now commonly known that possession of the epsilon4 allele of the apolipoprotein E (APOE) gene confers an increased risk for both familial and sporadic Alzheimer's disease (AD), in a dose-dependent way. Other genes that may play a role in AD, either through independent association with the disease or through modification of the existing APOE risk, have been reported with conflicting results. One such gene, the low density lipoprotein receptor-related protein (LRP) gene, was recently reported by two groups to be associated with AD, although the groups identified different risk-conferring alleles. Both studies were based on clinic-derived AD populations (one American, one French), and both reported only marginally significant results. We have genotyped a community-based AD and control population at this LRP polymorphism and find no association between the variants at that polymorphism and the occurrence of AD. Further, despite the biochemical relationship between LRP and the ApoE protein, we find no significant statistical interaction between the alleles at these loci.
Neuroscience Letters 10/1997; 233(2-3):145-7. · 2.11 Impact Factor
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Biological Psychiatry 02/1997; 41(2):246-8. · 8.28 Impact Factor
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ABSTRACT: In a previous publication the theory, procedure, and results of a method were described for making two sequential measurements of cerebral metabolic rate for glucose (CMRglc), within a 2-hr period, using [18F]fluorodeoxyglucose. The error that is specific to this technique was estimated using computer simulations. CMRglc for the second state was sensitive to errors in (a) the values of the rate constants, (b) alignment of PET slices between the two scans, and (c) subtraction of one PET image from another. The root mean square of the average error from each error source was 6.4%, which gives the theoretical reliability of this method. The measured reproducibility, taken from our previous publication, was 4.2-6.2%, which is in good agreement with the present result. This method contributes a small additional error above that expected for two independent scans. However, independent scans done on different days are likely to be subject to larger physiological variations in CMRglc than would occur using this method.
Journal of Nuclear Medicine 02/1989; 30(1):93-105. · 6.38 Impact Factor
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ABSTRACT: Positron emission tomographic (PET) scans using [18F]-fluorodeoxyglucose and magnetic resonance imaging (MRI) scans were quantitatively analyzed for metabolic and structural abnormalities in normal subjects and patients classified as having Alzheimer's disease (AD), mixed dementia and multi-infarct dementia (MID) according to Hachinski ischemic scores. MRI-detected abnormalities in the periventricular white matter and in subcortical locations increased in incidence with age in normals and increased markedly in AD and especially in MID. Upper limits for the severity of these white matter lesions could be defined only for normal young and elderly subjects, but not for AD, mixed or MID patients. PET scan abnormalities occurred in about 90% of demented patients and in 54% of elderly and 34% of young normals. There was no characteristic pattern of abnormality that distinguished MID from AD patients. It is concluded that PET and MRI studies in demented patients are useful ancillary tests especially in evaluating the mild, questionably demented subject and for assessing the functional impact of structural disease.
European Neurology 02/1989; 29 Suppl 3:9-15. · 1.81 Impact Factor
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ABSTRACT: We have developed a method that allows two sets of regional cerebral metabolic rates of glucose (rCMRglc) to be obtained in a single extended procedure using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). This is an adaptation of the deoxyglucose method, with the addition of a second injection of FDG immediately after completion of the first scan, then followed 30 min later by a second scan. A model has been developed to allow for correction of measured tracer concentration in the second scan by subtracting the predicted remnant from the first scan. The possible applications of this method in studying behavior-metabolism relationships are demonstrated. The preliminary results show 6%-12% changes in rCMRglc values for appropriate brain regions when the behavioral state is altered, but show 0%-5% change in rCMRglc values when the behavioral state is unchanged. The method can contribute significantly to the understanding of behavior-metabolism relationships by allowing the noninvasive study of two behavioral states in a single PET procedure.
Journal of Nuclear Medicine 06/1987; 28(5):852-60. · 6.38 Impact Factor
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ABSTRACT: When psychological activation is studied with PET using the deoxyglucose method, a stable and specific psychological state for at least 30 minutes is required before commencing the scan. At this time, if the subject reverts to the testing state, a progressive degradation of the activated pattern occurs. However, a strategy could be used to obtain corrected activation state data and resting state data in a single study using a tracer such as FDG. The amount of tracer FDG and FDG-6P in the tissue at the time of study completion, t, will be the sum of the remaining quantity (R) of tracer accumulated in the tissue at the time T, when activation ceases, and the uptake during the subsequent period t-T when resting state glucose transport kinetics apply.
04/1985
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ABSTRACT: Resting cerebral glucose metabolic rates (CMRglc) were measured in 23 subjects by PET using FDG. Subjects were divided into several groups (mean age +- S.D.) 5 young males (YM) (27 +- 6); 6 young females (YF)(33 +9); 5 elderly males (EM)(73 +- 5); 7 elderly females (EF)(69 +- 7). Additionally, from these groups 4 YM, 3YF, 5EM and 4EF were studied again within 6 weeks under identical conditions. CMRglc in the YF group again was significantly hider than YM (p 0.05). No obvious relationships of CMRglc to the phase of the menstrual cycle was found in this small group. There was a trend (p=0.06) toward a higher CMRglc in YF than EF. These results support the findings of higher CBF in YF versus YM. The differences between the results of Kuhl et al (J. Cereb. and a reduction of CMRglc with age was found in a mixed group of males and females (58and female), and where no age effect was found the males, are also resolved by these findings. The authors suggest that the apparent age effect, in females in this study, is principally a hormonal one.
04/1985
