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H Chui

Publications and source records attributed to H Chui.

At least 19 recordsLinked to original sources
PubMed2001

Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To update the 1994 practice parameter for the diagnosis of dementia in the elderly. BACKGROUND: The AAN previously published a practice parameter on dementia in 1994. New research and clinical developments warrant an update of some aspects of diagnosis. METHODS: Studies published in English from 1985 through 1999 were identified that addressed four questions: 1) Are the current criteria for the diagnosis of dementia reliable? 2) Are the current diagnostic criteria able to establish a diagnosis for the prevalent dementias in the elderly? 3) Do laboratory tests improve the accuracy of the clinical diagnosis of dementing illness? 4) What comorbidities should be evaluated in elderly patients undergoing an initial assessment for dementia? RECOMMENDATIONS: Based on evidence in the literature, the following recommendations are made. 1) The DSM-III-R definition of dementia is reliable and should be used (Guideline). 2) The National Institute of Neurologic, Communicative Disorders and Stroke--AD and Related Disorders Association (NINCDS-ADRDA) or the Diagnostic and Statistical Manual, 3rd edition, revised (DSM-IIIR) diagnostic criteria for AD and clinical criteria for Creutzfeldt--Jakob disease (CJD) have sufficient reliability and validity and should be used (Guideline). Diagnostic criteria for vascular dementia, dementia with Lewy bodies, and frontotemporal dementia may be of use in clinical practice (Option) but have imperfect reliability and validity. 3) Structural neuroimaging with either a noncontrast CT or MR scan in the initial evaluation of patients with dementia is appropriate. Because of insufficient data on validity, no other imaging procedure is recommended (Guideline). There are currently no genetic markers recommended for routine diagnostic purposes (Guideline). The CSF 14-3-3 protein is useful for confirming or rejecting the diagnosis of CJD (Guideline). 4) Screening for depression, B(12) deficiency, and hypothyroidism should be performed (Guideline). Screening for syphilis in patients with dementia is not justified unless clinical suspicion for neurosyphilis is present (Guideline). CONCLUSIONS: Diagnostic criteria for dementia have improved since the 1994 practice parameter. Further research is needed to improve clinical definitions of dementia and its subtypes, as well as to determine the utility of various instruments of neuroimaging, biomarkers, and genetic testing in increasing diagnostic accuracy.

Dementia↗
PubMed2001

Dementia due to subcortical ischemic vascular disease.

Ischemic vascular disease (IVD) is the second most common cause of dementia in the Western world. This article focuses on dementia resulting from subcortical ischemic vascular disease (SIVD), a subtype of IVD, which in many cases may be prevented. Hypertension and diabetes are the leading causes of small-artery disease, subcortical brain ischemia, and stepwise or slowing progressive decline in cognitive function. The pattern of cognitive impairment in SIVD, as compared with Alzheimer's disease, is characterized by greater impairment of executive function but better preservation of recognition memory. Structural neuroimaging studies, such as computed tomography and especially magnetic resonance imaging, are more sensitive than the clinical examination and can enable detection of subcortical lacunes and deep white matter changes that are clinically silent. Often the brain can be protected against SIVD by early diagnosis and management of risk factors. Once end-organ damage has occurred, however, treatment outcome is less satisfactory. The most common risk factors for SIVD--hypertension and diabetes mellitus--are best detected and managed in primary care settings.

Algorithms↗
PubMed2000

Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease.

BACKGROUND: The cause of dementia in subcortical ischemic vascular disease (SIVD) is controversial. OBJECTIVES: To determine whether cognitive impairment in SIVD 1) correlates with measures of ischemic brain injury or brain atrophy, and/or 2) is due to concomitant AD. METHODS: Volumetric MRI of the brain was performed in 1) elderly subjects with lacunes (L) and a spectrum of cognitive impairment-normal cognition (NC+L, n = 32), mild cognitive impairment (CI+L, n = 26), and dementia (D+L, n = 29); 2) a comparison group with probable AD (n = 28); and 3) a control group with normal cognition and no lacunes (NC). The authors examined the relationship between the severity of cognitive impairment and 1) volume, number, and location of lacunes; 2) volume of white matter signal hyperintensities (WMSH); and 3) measures of brain atrophy (i. e., hippocampal, cortical gray matter, and CSF volumes). RESULTS: Among the three lacune groups, severity of cognitive impairment correlated with atrophy of the hippocampus and cortical gray matter, but not with any lacune measure. Although hippocampal atrophy was the best predictor of severity of cognitive impairment, there was evidence for a second, partially independent, atrophic process associated with ventricular dilation, cortical gray matter atrophy, and increase in WMSH. Eight autopsied SIVD cases showed variable severity of ischemic and neurofibrillary degeneration in the hippocampus, but no significant AD pathology in neocortex. The probable AD group gave evidence of only one atrophic process, reflected in the severity of hippocampal atrophy. Comparison of regional neocortical gray matter volumes showed sparing of the primary motor and visual cortices in the probable AD group, but relatively uniform atrophy in the D+L group. CONCLUSIONS: Dementia in SIVD, as in AD, correlates best with hippocampal and cortical atrophy, rather than any measure of lacunes. In SIVD, unlike AD, there is evidence for partial independence between these two atrophic processes. Hippocampal atrophy may result from a mixture of ischemic and degenerative pathologies. The cause of diffuse cortical atrophy is not known, but may be partially indexed by the severity of WMSH.

Aged↗
PubMed2000

Head injury and the risk of AD in the MIRAGE study.

OBJECTIVES: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-epsilon4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. SUBJECTS: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study. METHODS: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses. RESULTS: Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking epsilon4 (OR = 3.3) than among epsilon4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3). CONCLUSION: Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE-epsilon4 compared with those having one or two epsilon4 alleles, suggesting that these risk factors may have a common biologic underpinning.

Aged↗
PubMed2000

Research criteria for subcortical vascular dementia in clinical trials.

Vascular dementia (VaD) incorporate different vascular mechanisms and changes in the brain, and have different causes and clinical manifestations. Variation in defining the cognitive syndrome, in vascular etiologies, and allowable brain changes in current clinical definitions of VaD have resulted in variable estimates of prevalence, of groups of subjects, and of the types and distribution of putative causal brain lesions. Thus current criteria for VaD select an etiologically and clinically heterogeneous group. This definitional heterogeneity may have been a factor in "negative" clinical trials. An alternative for clinical drug trials is to focus on a more homogeneous group, such as those with subcortical (ischemic) VaD. This designation incorporates two small vessel clinical entities "Binswanger's disease" and "the lacunar state". It comprises small vessel disease as the primary vascular etiology, lacunar infarct(s) and ischaemic white matter lesions as the primary type of brain lesions, and subcortical location as the primary location of lesions. The subcortical clinical syndrome is the primary clinical manifestation, a definition which still requires additional empirical data. We expect that subcortical VaD show a more predictable clinical picture, natural history, outcome, and treatment responses. We propose a modification of the NINDS-AIREN criteria as a new research criteria for subcortical VaD.

Clinical Trials as Topic↗
PubMed2000

Vascular dementia, a new beginning: shifting focus from clinical phenotype to ischemic brain injury.

Dementia may result from complete or incomplete infarction of brain regions subserving memory and cognition. Several effective treatments reduce the risk of initial and recurrent stroke. Presumably, these interventions reduce the risk of vascular cognitive impairment. Incomplete infarction caused by recurrent, chronic, or subclinical ischemia appears to represent another important cause of ischemic brain injury, but has been relatively neglected. A shift in focus from the serendipitous clinical phenotype of vascular dementia to preventing and ameliorating the broad spectrum of ischemic brain injury is recommended.

Aged↗
PubMed1999

Rigid point feature registration using mutual information.

We have developed a new mutual information-based registration method for matching unlabeled point features. In contrast to earlier mutual information-based registration methods, which estimate the mutual information using image intensity information, our approach uses the point feature location information. A novel aspect of our approach is the emergence of correspondence (between the two sets of features) as a natural by-product of joint density estimation. We have applied this algorithm to the problem of geometric alignment of primate autoradiographs. We also present preliminary results on three-dimensional robust matching of sulci derived from anatomical magnetic resonance images. Finally, we present an experimental comparison between the mutual information approach and other recent approaches which explicitly parameterize feature correspondence.

Algorithms↗
PubMed1999

Cerebral amyloid angiopathy in Alzheimer disease is associated with apolipoprotein E4 and cortical neuron loss.

Pathological correlations were sought between cerebral amyloid angiopathy (CAA) and other classical neurodegenerative changes in 101 consecutive cases of autopsy-confirmed Alzheimer disease (AD). Some degree of CAA was found in at least one area of the brain in 81% of the cases; severe CAA was found in at least one brain region in 29% of the cases. In a subset of 42 cases for which genomic DNA was available, greater severity of CAA was associated more with cases that were homozygous for apolipoprotein epsilon4 than in cases with only one or no epsilon4 alleles (Fisher's exact test, p = 0.005). In all brain regions, severity of CAA was inversely correlated with numbers of neurons. This correlation was statistically significant in the temporal lobe (r = -0.29,p = 0.004) and the frontal lobe (r = -0.22, p = 0.02). Our findings suggest that two factors may modify the severity of AD pathology: Apolipoprotein E4 may accentuate the vascular deposition of beta-amyloid, and severe CAA may accelerate neuronal loss.

Aged↗
PubMed1999

Magnetization transfer ratio of white matter hyperintensities in subcortical ischemic vascular dementia.

BACKGROUND AND PURPOSE: In subjects with subcortical ischemic vascular dementia (SIVD), tissue vacuolization, myelin pallor, and demyelination have been found on pathologic examination of white matter signal hyperintensities (WMSH). Magnetization transfer ratio (MTR) values provide a potential measure of compromised white matter integrity. The purpose of this study was to determine if there were differences in MTR of WMSH between subjects with SIVD and cognitively normal healthy control subjects. METHODS: Fifteen subjects with SIVD and 16 control subjects of comparable age and sex were studied. MTR images were coregistered to MR images segmented into tissue classes (gray matter, white matter, CSF, WMSH, and lacunar infarcts). MTR of WMSH was compared across groups and examined by WMSH location, size, and total burden. RESULTS: WMSH burden was greater in SIVD patients than in control subjects (2.4% vs 0.67%). MTR of WMSH did not differ between groups, but MTR of periventricular WMSH was lower in SIVD patients than in control subjects (37.6% vs 39.4%). Even after accounting for covariant effects of lesion burden, there was still a trend toward reduced periventricular WMSH MTR in the group with dementia. There was no correlation between WMSH MTR and WMSH lesion size. CONCLUSION: These findings are consistent with observations that pathologic changes in vascular dementia are most severe in the periventricular white matter and suggest that insight into the pathophysiology of SIVD might be gleaned from studies of the periventricular region.

Aged↗
PubMed1998

Ideomotor apraxia in early Alzheimer's disease: time and accuracy measures.

Twenty-six Alzheimer's disease (AD) and 42 healthy control (NC) subjects were evaluated with neuropsychological and apraxia batteries. ADs produced a greater range of error types, but did not differ from NCs in their most frequent error types. Hand sequencing ability contributed significantly to AD praxis with no predictors for NCs. Although groups did not differ in gesture time, the AD group had significantly longer response latencies for periods prior to gesture execution and the effect was prominent for transitive tasks and nondominant hand use. Results illustrate the sensitivity of timing measures in identifying abnormal praxis in early stages of AD.

Alzheimer Disease↗
PubMed1997

Potent alpha 4 beta 1 peptide antagonists as potential anti-inflammatory agents.

The migration, adhesion, and subsequent extravasation of leukocytes into inflamed tissues contribute to the pathogenesis of a variety of inflammatory diseases including asthma, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. The integrin adhesion receptor alpha 4 beta 1 expressed on leukocytes binds to the extracellular matrix protein fibronectin and to the cytokine inducible vascular cell adhesion molecule-1 (VCAM-1) at inflamed sites. Binding of alpha 4 beta 1 to VCAM-1 initiates firm adhesion of the leukocyte to the vascular endothelium followed by extravasation into the tissue. Monoclonal antibodies generated against either alpha 4 beta 1 or VCAM-1 can moderate this inflammatory response in a variety of animal models. Recently peptides containing a consensus LDV sequence based on the connecting segment-1 (CS-1) of fibronectin and cyclic peptides containing an RCD motif have shown promise in modulating leukocyte migration and inflammation presumably by blocking the interaction of alpha 4 beta 1 with VCAM-1. Here we describe novel, highly potent, cyclic peptides that competitively inhibit alpha 4 beta 1 binding to VCAM-1 and fibronectin at sub nanomolar concentrations. The structure of a representative analog was determined via NMR spectroscopy and used to facilitate optimization of peptide leads. The peptides discussed here utilize similar functional groups as the binding epitope of VCAM-1, inhibit lymphocyte migration in vivo, and are highly selective for alpha 4 beta 1. Furthermore the structure--activity relationships described here have provided a template for the structure-based design of small molecule antagonists of alpha 4 beta 1-mediated cell adhesion processes.

Animals↗
PubMed1997

A robust point-matching algorithm for autoradiograph alignment.

We present a novel method for the geometric alignment of autoradiographs of the brain. The method is based on finding the spatial mapping and the one-to-one correspondences (or homologies) between point features extracted from the images and rejecting non-homologies as outliers. In this way, we attempt to account for the local, natural and artifactual differences between the autoradiograph slices. We have used the resulting automated algorithm on a set of left prefrontal cortex autoradiograph slices, specifically demonstrated its ability to perform point outlier rejection, validated its robustness property using synthetically generated spatial mappings and provided an anecdotal visual comparison with the well-known iterated closest-point (ICP) algorithm. Visualization of a stack of aligned left prefrontal cortex autoradiograph slices is also provided.

Algorithms↗
PubMed1997

Evaluation of dementia: a systematic study of the usefulness of the American Academy of Neurology's practice parameters.

OBJECTIVE: This study examined the usefulness of the "Practice Parameters for the Evaluation of Dementia," published by the Quality Standards Subcommittee of the American Academy of Neurology (1994). The Practice Parameters are stratified according to three levels of certainty (standards, guidelines, and options), and suggest indications for the use of neuroimaging studies. METHODS: We reviewed 119 consecutive cases referred for assessment of memory loss to a university-affiliated interdisciplinary clinic. We assessed the diagnostic value of laboratory, neuropsychological, and neuroimaging studies above the standard history, neurologic, and mental status examinations. We also assessed the sensitivity and specificity of four clinical indicators (i.e., early symptom onset, noninsidious course, focal neurologic signs or symptoms, and gait disturbance) for predicting the diagnostic utility of neuroimaging studies. RESULTS: The largest changes in diagnostic categories between the standard and the comprehensive diagnostic process was a 9% decrease in the diagnosis of Alzheimer's disease, a 6% increase in the diagnosis of mixed dementia (due largely to laboratory studies), and a 4% increase in the diagnosis of vascular dementia (due to neuroimaging). The clinical indicators were 82% sensitive and 50% specific in predicting that neuroimaging studies would change the diagnosis. In six cases, meaningful neuroimaging findings were not associated with any clinical indicator (5% false negatives). In 43 cases, neuroimaging provided no significant clinical findings despite the presence of an indicator (36% false positives). CONCLUSIONS: In this convenience sample, diagnostic accuracy was improved to a comparable degree by laboratory and neuroimaging studies, although at a significant difference in cost. Use of the four clinical indicators would have reduced the frequency of neuroimaging studies by 33% but missed clinically meaningful information in 5%. Although imperfect, the Practice Parameters represent a first step toward improving the cost effectiveness of the dementia work-up.

Aged↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4.

Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one epsilon 4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking epsilon 4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband's APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility.

Adult↗
PubMed1993

Studies of the enteric nervous system in Alzheimer disease and other dementias of the elderly: enteric neurons in Alzheimer disease.

Studies of the myenteric (Auerbach) plexus of esophagus, stomach, small intestine, colon, and rectum, by microdissection and pointcount morphometry, for 18 patients with Alzheimer disease (AD), eight with other types of dementia of the elderly, non-demented elderly patients, and younger control patients, show a normal loss of enteric neurons and plexus mass with age, comparable to that reported by others for rats and guinea pigs. Values for patients with AD or other non-AD dementias did not differ from those for elderly controls. Enteric neurons in AD or the other dementias studied showed no definite stain with ALZ-50, a monoclonal antibody to a derivative of the microtubule-associated protein tau, which stains degenerating cerebral neurons in AD. Although the processes in the central nervous system in AD affect some neurons derived from the neural plate, the results of this study suggest that the enteric neurons, which are of neural crest origin, are not affected in AD. Enteric neurons, at least by the methods of this study, do not provide a useful peripheral marker for AD.

Age Factors↗
PubMed1991

Temporal and hippocampal metabolic rate during an olfactory memory task assessed by positron emission tomography in patients with dementia of the Alzheimer type and controls. Preliminary studies.

Positron emission tomography with fludeoxyglucose F 18 was used to assess cortical metabolic rate during an olfactory memory task in six patients with dementia of the Alzheimer type. Metabolic activity was compared with that of both age-matched controls performing the olfactory task and controls resting with their eyes closed. Patients had lower metabolic rates in the anterior portion of the medial-temporal cortex than did controls, and the difference was greatest between patients and the controls performing the memory task. This region is known to receive a large olfactory input and has been implicated in the encoding of human memory. Normal controls resting with their eyes closed had significantly lower metabolic rates in this area when compared with normal controls performing the task. Our results are consistent with those of earlier reports of temporal lobe decreases in metabolic rate and extend them through the examination of areas salient to the behavioral loss.

Aged↗