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R Katzman

Publications and source records attributed to R Katzman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease.

Our earlier studies had suggested a possible association between the HLA-A2 allele and Alzheimer's disease (AD). In the present study we tested the hypothesis that A2 is associated with earlier AD onset. We performed two independent studies: a collaborative study with 111 patients and a confirmatory study with 96 patients. We found similar patterns of reduced age at onset as a function of A2 in both data sets. Overall, A2 was associated with a significant 3-year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset appeared additive. Our results suggest A2, or a closely linked gene, modulates onset age of AD. Association with A2 would suggest an immune/inflammatory response mechanism for AD.

Age of Onset↗
PubMed1997

Effects of apolipoprotein E on dementia and aging in the Shanghai Survey of Dementia.

We investigated the status of the apolipoprotein E allele in 538 participants in the incidence phase of the ongoing Shanghai Survey of Dementia, including 103 demented subjects, 72 with mild cognitive impairment and 363 cognitively normal. The apo E epsilon 4 allele was present in 10.2% of control subjects and the allelic frequency did not change between ages 60 to 96 years. The apo E epsilon 4 allelic frequency was increased both in those wiht Alzheimer's disease (AD) (25.4%) and those with vascular dementia (VaD) (22.2%), but not in those with other dementing illnesses or the cognitively impaired. All of the subjects homozygous for apo E epsilon 4 were demented, three were diagnosed as having AD, and three met NINDS/AIREN criteria for VaD. The increased apo E epsilon 4 allelic frequency in clinically diagnosed VaD patients suggests that some of the infarcts are secondary to congophilic angiopathy. The adjusted odds ratio of developing AD in this community-derived study for persons with at least one apo E epsilon 4 allele was 4.1 (95% CI: 2.2, 7.7). Thus, the apo E epsilon 4 risk of developing AD in this Chinese cohort is similar to that in western community studies.

Age Factors↗
PubMed1996

Genetic studies in Alzheimer's disease with an NACP/alpha-synuclein polymorphism.

The non-Abeta component of Alzheimer's disease amyloid (NAC) is copurified with amyloid from the brain tissue of Alzheimer's disease victims and is immunohistochemically localized to amyloid fibrils. NAC is a hydrophobic peptide fragment from the NAC precursor protein (NACP/alpha-synuclein) that is localized to presynaptic terminals. We used a polymorphic dinucleotide repeat sequence in a genomic clone of NACP for genetic association and linkage studies. Screening of Alzheimer's disease families failed to establish linkage between NACP and Alzheimer's disease. Nevertheless, one of the NACP polymorphisms (NACP allele 2) was shown to have significant association with healthy elderly control individuals with apolipoprotein E risk. This may indicate a possible protective function of the allele.

Aged↗
PubMed1996

Neuropsychological deficits associated with diffuse Lewy body disease.

Diffuse Lewy body disease (DLBD), in its pure form, is a neuropathologic condition in demented patients that is characterized by subcortical and diffusely distributed neocortical Lewy bodies with little or no concomitant Alzheimer's disease (AD) pathology. Clinically, DLBD patients initially present with dementia of insidious onset and subsequently develop mild extrapyramidal motor dysfunction. The present study retrospectively examined the neuropsychological test performance of five patients with DLBD and compared their performance to that of equally demented patients with neuropathologically confirmed "pure" AD. The results showed that the DLBD patients were globally demented with deficits in memory, attention, language, psychomotor performance, and "executive" functions, and a strikingly severe deficit in visuospatial and visuoconstructive abilities. The visuoconstructive and psychomotor impairments of the DLBD patients were significantly worse than those of the AD patients, whereas the memory performance of the AD patients was worse than that of the DLBD patients. These results indicate that DLBD without concomitant AD pathology can produce a global dementia with aspects of both cortical and subcortical dysfunction and suggests that Lewy body pathology contributes importantly to the clinical manifestation of the Lewy body variant of AD.

Aged↗
PubMed1996

Clinical and neuropathological findings in Lewy body dementias.

We compared clinical features in three groups of pathologically defined patients evaluated for dementia during life: (i) Alzheimer's disease (AD); (ii) Lewy body variant of Alzheimer's Disease (LBV), with Lewy bodies (LB) and AD; (iii) diffuse Lewy body disease (DLBD), with LB alone. All three groups had similar initial cognitive symptoms. LBV and DLBD had Parkinsonian signs, though resting tremor was extremely rare. Delusions and hallucinations were relatively more frequent in LBV and DLBD than in AD. On neuropsychological testing, the LBV group had relatively greater impairment than AD on visuospatial and executive tests. LB therefore contribute to the clinical picture of dementia.

Aged↗
PubMed1996

The apolipoprotein E epsilon 4 allele is associated with increased neuritic plaques and cerebral amyloid angiopathy in Alzheimer's disease and Lewy body variant.

OBJECTIVE: To determine the relationship between apolipoprotein E (apoE) genotype and neuropathologic lesions in Alzheimer's disease (AD) and Lewy body variant (LBV). DESIGN: Retrospective genetic-neuropathologic study of AD and LBV cases. The main neuropathologic outcome measures were modeled as a function of apoE genotype, neuropathologic diagnosis, and gender. Age at death and duration of symptom effects were controlled for by ANCOVA. PATIENTS: One hundred twenty-seven cases with neuropathologically diagnosed AD (n = 84) or LBV (n = 43). MAIN OUTCOME MEASURES: Quantitative scores of neuritic plaques (NPs), neurofibrillary tangles (NFTs), cerebral amyloid angiopathy (CAA) severity, and CAA prevalence were averaged across four brain regions: midfrontal, inferior parietal, superior temporal, and hippocampal. RESULTS: The apoE epsilon 4 allele was associated with increased NPs within both AD and LBV. The epsilon 4 allele was associated with an increased frequency of CAA in the AD and LBV groups combined groups combined and in and in LBV alone. While CAA severity and NETs were increased in the epsilon 4/4 homozygous case when AD and LBV were combined, there were no significant effects within AD or LBV alone. CONCLUSIONS: The apoE epsilon 4 allele is strongly associated with increased NPs, but not neocortical NFTs, in both AD and LBV.

Aged↗
PubMed1995

Cerebral infarction in Alzheimer's disease is associated with severe amyloid angiopathy and hypertension.

OBJECTIVE: To determine if severe cerebral amyloid angiopathy (AA) in patients with Alzheimer's disease (AD) is associated with an increased prevalence of cerebral infarction diagnosed at autopsy. Amyloid angiopathy is increasingly recognized as a cause of ischemic infarcts, as well as cerebral hemorrhages. However, the relationship of AA to cerebral infarction in patients with AD is uncertain. DESIGN: Retrospective clinicopathological study of autopsy-confirmed cases of AD. PATIENTS: One hundred forty-five deceased patients with AD confirmed at autopsy. MAIN OUTCOME MEASURES: Semiquantitative scores of AA severity were done in four brain regions: midfrontal, inferior parietal, superior temporal, and hippocampal. The finding of cerebral infarction at autopsy was modeled as a function of AA severity, hypertension, age at death, AD severity, and sex in chi 2 and multiple logistic regression analyses. RESULTS: Severe AA was significantly associated with cerebral infarction at autopsy in patients with AD (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.4 to 8.9). None of the other independent variables in the multiple logistic regression analysis were significant predictors. While hypertension was equally common in the severe and mild AA subgroups, the combination of both severe AA and hypertension interacted to increase the risk of infarction (OR, 14.2; 95% CI, 3.2 to 63.4) beyond that observed with hypertension (OR, 1.1; 95% CI, 0.4 to 3.2) or severe AA (OR, 1.3; 95% CI, 0.3 to 5.3) alone. CONCLUSIONS: Severe AA is associated with an increased frequency of cerebral infarction in patients with AD. This appears to be largely due to an interaction between severe AA and hypertension that may produce multiplicative injuries on the vasculature. Further study with regard as to how AA may cause ischemia and its role in the neuropathologic and clinical progression of AD is needed.

Aged↗
PubMed1995

The CYP2D6B mutant allele is overrepresented in the Lewy body variant of Alzheimer's disease.

Approximately one-fourth of neuropathologically confirmed cases of Alzheimer's disease (AD) also have brainstem and neocortical Lewy bodies, constituting a Lewy body variant of AD. Because Lewy bodies are a pathologic hallmark of Parkinson's disease (PD), this subpopulation of AD subjects may have the same risk factors as PD subjects. Analyses of the cytochrome P450 CYP2D6-debrisoquine 4-hydroxylase mutant B allele, a susceptibility gene for PD, revealed a higher representation of this allele in the Lewy body variant of AD than in pure AD or non-AD without Lewy bodies.

Alleles↗
PubMed1995

The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's disease.

Both genetic and environmental factors affect the progression of Alzheimer's disease (AD). The presence of cortical Lewy bodies in AD patients is associated with an altered presentation of AD pathology suggestive of an interaction between the pathogenesis of Lewy bodies and AD lesions. Since the CYP2D6B mutant allele is often present in patients with Lewy body diseases (Parkinson's disease and Lewy body variant of AD), we extended these prior observations by studying the neuropathology associated with the presence of the CYP2D6B mutant allele in a pure AD population without Lewy bodies. AD patients who possessed the CYP2D6B mutant allele, in comparison with those without the CYP2D6B allele, were found to have a smaller decline in two synaptic markers, choline acetyltransferase and synaptophysin, in the frontal cortex relative to normal control values. On the other hand, senile plaques and neurofibrillary tangles were not significantly affected by the presence of the CYP2D6B mutant allele in the frontal cortex of AD patients. Association of the CYP2D6B mutant allele with Lewy body formation in both Parkinson's disease and the Lewy body variant of AD and with the milder synaptic pathology in pure AD without Lewy bodies suggest that depending on the contribution of other genetic and environmental factors, this mutant allele may be involved with different aspects of neurodegeneration.

Aged↗
PubMed1995

Genetic evidence that the Lewy body variant is indeed a phenotypic variant of Alzheimer's disease.

Lewy Body Variant (LBV) patients present as Alzheimer's disease (AD) clinically; about two-thirds also have mild extrapyramidal features. At autopsy, neocortical and brain stem Lewy bodies are present in addition to changes diagnostic of AD. We have found that the Apolipoprotein E4 allele is a major genetic risk factor for LBV as it is for "pure AD," in contrast to subjects with diffuse Lewy body disease or Parkinson's disease. This genetic evidence supports the concept that LBV--the second most common neurodegenerative form of dementia--is a phenotypic variant of AD.

Aged↗
PubMed1995

ADL dependence and medical conditions in Chinese older persons: a population-based survey in Shanghai, China.

OBJECTIVE: To describe the prevalence of activities of daily living (ADL) dependence and medical conditions and the relationship between illnesses and ADL performance in the older population of Shanghai, China. DESIGN: Probability sample survey of community residents. SETTING: The Jing An district of Shanghai, China. The interviews were carried out at the homes of the older persons. PARTICIPANTS: There were 3763 noninstitutionalized elders screened, 3745 of whom completed the interview. MEASUREMENTS: The dependent variables were the five basic ADL items: eating, dressing, transferring, toileting, and bathing. The independent variables were dementia and 19 self-reported medical conditions, along with age, gender and education level. MAIN RESULTS: Of those in Shanghai aged 65 and older, 8.28% (6.52% of males, 9.17% of females) were functionally dependent in one or more ADLs. The most prevalent self-reported illness was cardiovascular disease, including hypertension (29.12%) and heart disease (26.65%). ADL performance was associated with dementia and a number of medical conditions in univariate analysis. The best predictors of functional dependence in both age groups (65-74 years; 75 years and older), based on the multiple logistic regression analysis and after controlling for age, gender, and education, were stroke, dementia, Parkinson's disease, diabetes, and emphysema. CONCLUSIONS: The authors have successfully applied five ADL items selected and culturally adapted from Older Americans Resources and Services to the study of older Chinese. A consistent and reliable estimate of functional dependence among older persons is obtained. The prevalence of dementia and many self-reported illness, as well as the ADL status by medical condition, are reported. The findings reveal certain patterns of relationship between illness conditions and ADL performance.

Activities of Daily Living↗
PubMed1994

Clinical-neuropathological correlations in Alzheimer's disease and related dementias.

OBJECTIVE: To compare neurologists' initial clinical diagnoses made according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition guidelines with neuropathological diagnoses of Alzheimer's disease (AD) and related dementias. DESIGN: Consecutive autopsies in a prospective cohort study. SETTING: Community-dwelling patients with dementia referred to neurologists at an Alzheimer's Disease Research Center and satellite clinics (n = 151) and patients initially evaluated when institutionalized (n = 19). PATIENTS: Of 204 elderly patients who had an autopsy performed, 170 had received a complete dementia evaluation according to NINCDS-ADRDA guidelines. MAIN OUTCOME MEASURES: Percentage agreement between neurologists' initial clinical diagnoses and pathological findings. RESULTS: Of 137 patients clinically diagnosed as having probable or possible AD, 123 (90%) had AD neuropathological findings; this included 29 with AD accompanied by Lewy bodies, and 14 with AD and one or more infarcts. Cases of vascular and mixed dementia (AD and infarct[s]) had lower rates of agreement with pathological findings. Possible AD cases were more likely than probable AD cases to show pathological features other than AD. Clinicians predicted the presence or absence of AD pathological findings significantly better than chance. In patients with AD pathological lesions, older age of onset and male gender were significantly associated with shorter duration from disease onset to death. CONCLUSIONS: Clinicians accurately predicted AD pathological findings or their absence in most cases. Attributing other degenerative dementias to AD, misdiagnosing patients with combined AD and Lewy bodies and misjudging the vascular contribution to dementia were the major areas of inaccuracy. Formal criteria for dementia associated with non-AD lesions, Lewy bodies, and infarcts need to be developed and tested.

Aged↗
PubMed1994

The malignancy of dementia. Predictors of mortality in clinically diagnosed dementia in a population survey of Shanghai, China.

OBJECTIVE: To evaluate the effect of dementing illnesses on the risk of dying, taking into account other conditions that would shorten survival. DESIGN: Five-year follow-up of community survey of dementia. SETTING: Five-year data were obtained for the 3531 subjects, aged 65 years and older, who participated in the 1987 population survey of dementia in Shanghai, China. MAIN OUTCOME MEASURE: Time to death. Relative risks of dying were calculated for demographic variables, dementia diagnoses based on findings of clinical evaluations, and 15 reported prevalent medical conditions using the proportional hazards model. RESULTS: In those subjects aged 65 to 74 years, the mortality risk ratio was 5.4 (95% confidence interval, 2.0 to 14.6) for Alzheimer's disease and 7.2 (95% confidence interval, 3.6 to 14.4) for vascular dementia. The risk ratio for Alzheimer's disease was similar to the mortality risk ratio for cancer (5.6 [range, 2.9 to 10.9]). In this age group, dementing illnesses were uncommon, and few deaths were therefore attributable to the dementing illnesses. In those subjects aged 75 years and older, the mortality risk ratios were 2.8 (95% confidence interval, 2.1 to 3.6) for Alzheimer's disease, 3.5 (95% confidence interval, 2.4 to 5.1) for vascular dementia, and 3.6 (95% confidence interval, 2.0 to 6.7) for "other dementias." Because these dementing disorders were common in those subjects aged 75 years and older, 23.7% of the risk of death could be attributed to these disorders. CONCLUSIONS: Both Alzheimer's disease and vascular dementias are truly malignant and constitute major risk factors for death in persons older than 75 years.

Aged↗
PubMed1994

Association of education with incidence of cognitive impairment in three established populations for epidemiologic studies of the elderly.

We analyzed the association of education, occupation, and sex with incidence of cognitive impairment using data from three communities in the Established Populations for Epidemiologic Studies of the Elderly (EPESE) projects (New Haven, East Boston, and Iowa). Participants were initially interviewed in 1981-1983, with follow-up 3 and 6 years later. Incident cognitive impairment was defined on the basis of either: (1) increase in the number of errors in Short Portable Mental Status Questionnaire (SPMSQ) (i.e. from a baseline level below the cutoff value to a score above the cutoff), or (2) inability to respond to interview questions at a follow-up contact (requiring a proxy informant), or (3) death with a recorded diagnosis of a dementing illness. In multiple logistic regression models, the major factors predicting the development of cognitive impairment were advanced age, any errors on baseline SPMSQ, 8 or fewer years of education, and occupation. Education and occupation remained significant predictors after controlling for age, site, sex, stroke, and baseline SPMSQ score.

Aged↗
PubMed1994

Apolipoprotein E and Alzheimer's disease.

The past year has seen widespread confirmation that the epsilon 4 allele of the apolipoprotein E gene is a major risk factor for Alzheimer's disease. The epsilon 4 allele also appears to correlate with life expectancy. This allele has been found to be present in over 50% of Alzheimer patients, regardless of whether or not they have a family history of dementia. It is not yet clear how the epsilon 4 allele mediates its actions; however, recent evidence suggests that apolipoprotein E4 may be responsible for the accelerated formation of beta-pleated amyloid from soluble beta-amyloid peptide, as is seen in the neuritic plaques of Alzheimer patients, as well as interacting with intraneuronal microtubular transport mechanisms.

Alleles↗