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David Knopman

Publications and source records attributed to David Knopman.

14 recordsLinked to original sources
PubMed2006

CHMP2B mutations are not a common cause of frontotemporal lobar degeneration.

It was reported in 1995 that a large Danish family with familial frontotemporal dementia (FTD) was linked to the pericentromeric region of chromosome 3. It has since been claimed that a mutation in the splice acceptor site of exon 6 of CHMP2B is the pathogenic variant in this family. In order to determine whether CHMP2B mutations are a common cause of disease in patients with frontotemporal lobar degeneration (FTLD) we sequenced all exons and flanking regions of CHMP2B in 141 familial FTLD probands from the USA and UK. We failed to find a single pathogenic variant in any case. Polymorphisms were detected but were present in control samples. We conclude that mutations in CHMP2B are a rare cause of familial FTLD and may be specific to the Danish pedigree.

Dementia↗
PubMed2004

Addressing the ethical, legal, and social issues raised by voting by persons with dementia.

This article addresses an emerging policy problem in the United States participation in the electoral process by citizens with dementia. At present, health care professionals, family caregivers, and long-term care staff lack adequate guidance to decide whether individuals with dementia should be precluded from or assisted in casting a ballot. Voting by persons with dementia raises a series of important questions about the autonomy of individuals with dementia, the integrity of the electoral process, and the prevention of fraud. Three subsidiary issues warrant special attention: development of a method to assess capacity to vote; identification of appropriate kinds of assistance to enable persons with cognitive impairment to vote; and formulation of uniform and workable policies for voting in long-term care settings. In some instances, extrapolation from existing policies and research permits reasonable recommendations to guide policy and practice. However, in other instances, additional research is necessary.

Civil Rights↗
PubMed2004

Confrontation naming does not add incremental diagnostic utility in MCI and Alzheimer's disease.

As the incidence of dementia increases, there is a growing need to determine the diagnostic utility of specific neuropsychological tests in the early diagnosis of Alzheimer's disease (AD). In this study, the relative utility of Boston Naming Test (BNT) in the diagnosis of AD was examined and compared to the diagnostic utility of other neuropsychological measures commonly used in the evaluation of AD. Individuals with AD (n = 306), Mild Cognitive Impairment (MCI; n = 67), and cognitively normal subjects (n = 409) with at least 2 annual evaluations were included. Logistic regression analysis suggested that initial BNT impairment is associated with increased risk of subsequent AD diagnosis. However, this risk is significantly less than that imparted by measures of delayed recall impairments. A multivariate Cox proportional hazards regression analysis suggested that BNT impairment imparted no additional risk for subsequent AD diagnosis after delayed recall impairments were included in the model. Although BNT impairment occurred in all severity groups, it was ubiquitous only in moderate to severe dementia. Collectively these results suggest that although BNT impairments become more common as AD progresses, they are neither necessary for the diagnosis of AD nor particularly useful in identifying early AD.

Aged↗
PubMed2003

Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses?

BACKGROUND: Tau and beta-amyloid (Abeta) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific pathology, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects. OBJECTIVES: To correlate antemortem cerebrospinal fluid (CSF) tau and Abeta levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Abeta. DESIGN: Prospective study. SETTING: Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects. MAIN OUTCOME MEASURES: Correlation of CSF tau and Abeta with final diagnosis. RESULTS: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Abeta42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL). CONCLUSIONS: Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean +/- 2 SDs of the cognitively normal cohort.

Adult↗
PubMed2003

Cognitive functioning as a predictor of ischemic stroke incidence.

BACKGROUND: Some studies have suggested that cognitive impairment is related to subsequent stroke incidence. The present study investigated the role of cognitive impairment as a predictor of ischemic stroke incidence in the Atherosclerosis Risk in Communities (ARIC) cohort. METHODS: The study population consisted of 11,958 men and women 48-67 years of age in 4 U.S. communities, followed from January 1, 1990 through December 31, 1997. Cognitive performance was evaluated at the second (1990-1992) visit of the ARIC Study using 3 instruments. We identified incident strokes by means of hospital record and death certificate reviews, as well as annual telephone follow up. RESULTS: We found no consistent associations or trends between any of the cognitive test results and ischemic stroke incidence after multiple adjustment for confounding variables. Hazard ratios for the lowest compared with the highest quartiles were 1.5 (95% confidence interval [CI] = 0.9-2.6), 1.1 (95% CI = 0.6-2.1), and 1.0 (95% CI = 0.6-1.8) for the Delayed Word Recall Test, Digit Symbol Subtest of the Wechsler Adult Intelligence Scale-Revised, and Word Fluency Test, respectively. CONCLUSIONS: The findings of the present study of relatively young subjects did not replicate the association between cognitive impairment and stroke incidence found in studies in older populations. This could be the result of the younger ages of our cohort members or the differences in cognitive tests.

Aged↗
PubMed2002

The relationship between temporal changes in blood pressure and changes in cognitive function: atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Although previous epidemiological studies have reported that hypertension is a major risk factor for decline in brain perfusion and atrophy, which are known to be related to cognitive decline, the impact of temporal changes in blood pressure on age-related cognitive declines has not been assessed. METHODS: The present study evaluates changes in blood pressure and cognitive decline over a 6-year period in the Atherosclerosis Risk in Communities (ARIC) Study. This report is based on 8,058 men and women aged 48-67 years examined in the second (1990-92), and fourth (1996-98) ARIC cohort visits. Changes between these visits were measured in hypertension status and three cognitive function tests: Delayed Word Recall (DWR), the Digit Symbol Subtest of the Wechsler Adult Intelligence Scale-Revised (DSS/WAIS-R), and the Word Fluency (WF). Adjusted mean differences in cognitive function were compared among five categories of hypertension status by using linear regression modeling. RESULTS: In the present study, older subjects with uncontrolled hypertension had a significantly larger mean DSS/WAIS-R score decline than normotensive subjects. Although other cognitive declines did not achieve statistical significance, both cross-sectional and change analysis suggested that partially controlled or uncontrolled hypertension is associated with a less favorable cognitive profile, particularly when considering results of the DSS and the WF tests. CONCLUSIONS: The present study results provide some support to the hypothesis that hypertension status changes over 6 years in individuals initially aged 48-67 years are related to cognitive changes.

Aged↗
PubMedDate not supplied

Pharmacotherapy for Alzheimer's disease: 2002.

The intensity of interest in therapy for Alzheimer's disease (AD) has accelerated with each passing year. The nature of the effects of cholinesterase inhibitors has been refined with the publication of several studies that have examined long-term therapy as well as different aspects of the symptomatology of AD. Breakthroughs in the basic science of AD has led to new insights into potential therapeutic strategies targeted at the secretases involved in the metabolism of the Alzheimer precursor protein. An immunization approach in which the amyloid-beta protein itself was used as the immunizing agent was discontinued after unexpected toxicity occurred. Other areas of investigation with disappointing results such as estrogen replacement therapy and antiinflammatory approaches are discussed. Several other potential therapeutic agents are also reviewed.

Alzheimer Disease↗