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H Chui

Publications and source records attributed to H Chui.

18 recordsLinked to original sources
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↗
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↗
PubMed1989

Phenotypic heterogeneity in familial Alzheimer's disease: a study of 24 kindreds.

We report the clinical and neuropathological characteristics occurring in 180 demented individuals from 24 kindreds with familial Alzheimer's disease (FAD). Each family had at least two affected generations, and at least one autopsy or brain biopsy was compatible with the diagnosis of AD. Forty-nine neuropathological specimens or reports were reviewed. Mean age of onset for the total group was 54.7 years +/- 11.5, with a large range of 30 to 84 years. Mean age at death was 63.5 years +/- 12.2, with a range of 46 to 85. Mean duration of disease was 8.8 years +/- 4.4, with a range of 1 to 23 years. Six findings suggested phenotypic heterogeneity in FAD. (1) Five families represented an early age of onset group with mean onset at 42 years (range 30 to 51 years) and mean disease duration of 6.7 years. (2) Eight families represented a late onset group with mean onset at 68 years (range 59 to 78 years) and a mean duration of 8.5 years. (3) Seven families were of Volga German ancestry, all originating from the same two villages in Russia. Mean age of onset was 55.9 years (range 40 to 72 years), with a mean disease duration of 10 years. This group probably represents the genetic founder effect of an autosomal dominant gene for AD. (4) One family had the unusual characteristics of neurofibrillary tangles and granulovacuolar change but no amyloid plaques, a mean disease duration of more than 11 years, and a "schizophrenia-like" onset. (5) One family with late onset also had clinical and pathological evidence for anterior horn cell disease. (6) Two autopsies in 1 family both showed remarkable rarefaction of myelin and expansion of perivascular spaces in centrum semiovale (état criblé), with marked leptomeningeal and cortical amyloid angiopathy, distinct from the other FAD brains. It remains to be determined whether the clinical and pathological differences between these families represent genetic heterogeneity at the biochemical or molecular level.

Adult↗
PubMed1988

Functional recovery. A major risk factor for the development of postpoliomyelitis muscular atrophy.

A retrospective study was undertaken to identify potential risk factors for the development of progressive postpoliomyelitis muscular atrophy (PPMA). Patients with PPMA (n = 57) were compared with patients with a history of poliomyelitis but without a history of progressive weakness (n = 49). Patients who later developed PPMA had histories of more widespread acute paralysis, but relatively greater functional recovery. They were less disabled, and reported higher recent activity levels. Seventy-nine percent of the total variance between the PPMA and control groups could be accounted for by recovery alone (ie, severity minus disability). Functional recovery is generally attributed to reinnervation of sarcomeres by collateral sprouting from surviving lower motor neurons. Since degree of recovery predicts the risk of developing PPMA, our findings suggest that enlarged motor units may carry an increased susceptibility for dysfunction and/or degeneration.

Adult↗
PubMed1983

Churg-Strauss syndrome (allergic granulomatous angiitis). Neuro-ophthalmologic manifestations.

Two patients with severe bronchial asthma, hypereosinophilia, and peripheral neuropathy were initially observed with neuro-ophthalmologic signs and symptoms that included amaurosis fugax, superior oblique palsy, ischemic optic neuropathy, and scattered areas of retinal infarction. Clinical investigation led to the diagnosis of Churg-Strauss syndrome (allergic granulomatous angiitis). As in other collagen vascular diseases, ocular signs or symptoms may occasionally be the most prominent manifestation of the disease. Recognition of this systemic disorder by the ophthalmologist may minimize systemic and ocular complications.

Asthma↗
PubMedDate not supplied

Natural history of vascular dementia.

Knowledge about the natural history of vascular dementia (VaD) provides one context for assessing efficacy in pharmacological drug trials. We reviewed the literature for original studies reporting either (a) duration of survival or (b) cognitive status following a diagnosis of multi-infarct dementia (MID). Among 13 papers (combined sample size = 470; mean duration of follow-up = 4.3 years), survival was significantly shorter following a clinical diagnosis of MID compared with Alzheimer disease (AD). Nine studies (combined sample size = 175; mean duration of follow-up = 2.9 years) reported at least two mental status scores separated by at least 1 year. Among four studies using the Mini-Mental State Examination, no consistent differences in annualized rate of decline could be observed for MID compared with AD. Also, no factors were identified that predict rate of decline. This review reveals many limitations in our current knowledge about the natural history of VaD. Understanding would be enhanced by multinational harmonization of definitions for study entry point, diagnosis of VaD, classification of subtypes, as well as cognitive, functional, and behavioral endpoints.

Cognition Disorders↗