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Ronald C Petersen

Publications and source records attributed to Ronald C Petersen.

At least 37 records · Page 2Linked to original sources
PubMed2006

Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study.

BACKGROUND: It remains unknown whether depression and apolipoprotein E genotype are risk factors for incident mild cognitive impairment (MCI). OBJECTIVE: To determine whether elderly individuals with depression (measured by the short Geriatric Depression Scale) are at increased risk of developing incident MCI. DESIGN: Prospective cohort study. SETTING: Primary care clinic. PARTICIPANTS: A cohort of 840 cognitively normal elderly subjects without depression at recruitment who were followed up prospectively for a median of 3.5 years (range, 0.4-12.8 years). Subjects who developed depression (score of >/=6 on the short Geriatric Depression Scale; depression cohort) were compared with all remaining subjects (referent cohort). MAIN OUTCOME MEASURES: Incidence of MCI (primary outcome) and incidence of MCI or dementia (composite secondary outcome). RESULTS: Individuals in the depression cohort were at significantly increased risk of subsequent incident MCI (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1) after adjusting for age (time scale), sex, and education, and considering dementia as a competing outcome. The association was stronger in men but did not vary by severity of depression. We observed a synergistic interaction between apolipoprotein E genotype (epsilon3/epsilon4 or epsilon4/epsilon4) and depression (joint effect HR, 5.1; 95% CI, 1.9-13.6; test for additive interaction, P = .03). We found a similar association between depression and the subsequent composite outcome of incident MCI or dementia (HR, 2.6; 95% CI, 1.6-4.3). CONCLUSIONS: Cognitively normal elderly individuals who develop depression are at increased risk of subsequent MCI. We found a synergistic interaction between depression and apolipoprotein E genotype.

Aged↗
PubMed2006

Clinically undetected motor neuron disease in pathologically proven frontotemporal lobar degeneration with motor neuron disease.

BACKGROUND: Frontotemporal lobar degeneration with motor neuron disease (FTLD-MND) is a pathological entity characterized by motor neuron degeneration and frontotemporal lobar degeneration. The ability to detect the clinical signs of dementia and motor neuron disease in pathologically confirmed FTLD-MND has not been assessed. OBJECTIVES: To determine if all cases of pathologically confirmed FTLD-MND have clinical evidence of frontotemporal dementia and motor neuron disease, and to determine the possible reasons for misdiagnosis. METHOD: Review of historical records and semiquantitative analysis of the motor and extramotor pathological findings of all cases of pathologically confirmed FTLD-MND. RESULTS: From a total of 17 cases of pathologically confirmed FTLD-MND, all had clinical evidence of frontotemporal dementia, while only 10 (59%) had clinical evidence of motor neuron disease. Semiquantitative analysis of motor and extramotor pathological findings revealed a spectrum of pathological changes underlying FTLD-MND. Hippocampal sclerosis, predominantly of the subiculum, was a significantly more frequent occurrence in the cases without clinical evidence of motor neuron disease (P<.01). In addition, neuronal loss, gliosis, and corticospinal tract degeneration were less severe in the other 3 cases without clinical evidence of motor neuron disease. CONCLUSIONS: Clinical diagnostic sensitivity for the elements of FTLD-MND is modest and may be affected by the fact that FTLD-MND represents a spectrum of pathological findings, rather than a single homogeneous entity. Detection of signs of clinical motor neuron disease is also difficult when motor neuron degeneration is mild and in patients with hippocampal sclerosis.

Adult↗
PubMed2006

Neuropathologic features of amnestic mild cognitive impairment.

BACKGROUND: The neuropathologic substrate of amnestic mild cognitive impairment (aMCI) is not known. OBJECTIVE: To determine the neuropathologic features of patients who died while their clinical classification was aMCI. DESIGN: Cohort study. SETTING: Community based. PARTICIPANTS: Sixty-six individuals, including 15 who had memory impairment beyond that allowed for aging but who were not demented, were studied along with 28 clinically healthy individuals and 23 patients with probable Alzheimer disease (AD) for comparison. MAIN OUTCOME MEASURES: Standard neuropathologic techniques and classification according to Khachaturian, Consortium to Establish a Registry for Alzheimer Disease, and National Institute on Aging-Reagan criteria were used to analyze autopsy tissue from 15 individuals who died while their clinical diagnosis was aMCI. For comparison, autopsy data on age-matched groups of clinically healthy individuals and patients with probable AD were analyzed. RESULTS: Most patients with aMCI did not meet the neuropathologic criteria for AD, but their pathologic findings suggest a transitional state of evolving AD. All the patients with aMCI had pathologic findings involving medial temporal lobe structures, likely accounting for their memory impairment. In addition, there were many concomitant pathologic abnormalities, including argyrophilic grain disease, hippocampal sclerosis, and vascular lesions. CONCLUSIONS: The neuropathologic features of aMCI matched the clinical features and seemed to be intermediate between the neurofibrillary changes of aging and the pathologic features of very early AD.

Aged↗
PubMed2006

Neuropathologic outcome of mild cognitive impairment following progression to clinical dementia.

BACKGROUND: The pathologic outcome of patients diagnosed with mild cognitive impairment (MCI) following progression to dementia is poorly understood. OBJECTIVE: To determine the pathologic substrates of dementia in cases with prior diagnosis of amnestic MCI. DESIGN AND SETTING: Community-based cohort. PATIENTS: Thirty-four subjects followed up prospectively as part of a community-based study who were diagnosed with amnestic MCI, progressed to clinical dementia, and underwent subsequent postmortem brain analysis. MAIN OUTCOME MEASURES: Neuropathologic analyses resulted in assignment of a primary pathologic diagnosis and included staging of Alzheimer pathologic abnormalities and identification of contributing vascular disease, Lewy bodies, and argyrophilic grains. RESULTS: Although the majority of subjects progressed both clinically and pathologically to Alzheimer disease (AD), 10 (29%) of them developed non-AD primary pathologic abnormalities. All of the cases were found to have sufficient pathologic abnormalities in mesial temporal lobe structures to account for their amnestic symptoms regardless of the cause. Most subjects were found to have secondary contributing pathologic abnormalities in addition to primary pathologic diagnoses. No significant differences between subjects with and without neuropathologically proven AD were detected in demographic variables, apolipoprotein E genotype, or cognitive test measures at onset of MCI, onset of dementia, or last clinical evaluation. CONCLUSIONS: The neuropathologic outcome of amnestic MCI following progression to dementia is heterogeneous, and it includes AD at a high frequency. Complex neuropathologic findings including 2 or more distinct pathologic entities contributing to dementia may be common in community-based cohorts. Neither demographic variables nor cognitive measures had predictive value in determining which patients diagnosed with MCI will develop the neuropathologic features of AD.

Aged↗
PubMed2006

Cognitive measures predict pathologic Alzheimer disease.

BACKGROUND: Neuropsychologic testing is often used to infer neuropathologic processes, but clinicopathologic correlations for individual cognitive measures are based on a small number of published studies. OBJECTIVE: To examine the usefulness of the age- and education-adjusted Mayo Cognitive Factor Scales (MCFS) obtained at participants' initial assessments for predicting the presence or absence of pathologic Alzheimer disease (AD). DESIGN: This was a longitudinal study of a cohort of elderly patients with and without cognitive complaints who were followed up until death. Mayo Cognitive Factor Scales age- and education-adjusted standard scores from the participants' initial evaluations were used to calculate classification accuracy statistics for neuropathologic AD diagnosis obtained approximately 6 years after testing. Subjects with non-AD diagnoses or substantial non-AD-related changes were excluded from the study. SETTING: Academic medical center. PARTICIPANTS: One hundred two participants were evaluated clinically and underwent neuropathologic examination at autopsy. All were part of the Mayo Clinic Alzheimer's Disease Patient Registry or Alzheimer Disease Research Center. RESULTS: All Mayo Cognitive Factor Scale scores were significantly correlated with AD criteria. Logistic regression modeling including Mayo Cognitive Factor Scales Verbal Comprehension and Retention indices revealed high positive predictive value with moderate sensitivity and specificity for pathologic AD. CONCLUSION: Neuropsychologic test scores at initial evaluations were predictive of pathologic AD.

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PubMed2006

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

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PubMed2006

Neuropsychological differentiation of dementia with Lewy bodies from normal aging and Alzheimer's disease.

We examined the diagnostic utility of selected neuropsychological measures in the differentiation of dementia with Lewy bodies (DLB) from normal aging and Alzheimer's disease (AD). Patients with DLB (n = 87), AD (n = 138), and a group of normal controls (n = 103) were recruited from the Mayo Alzheimer's disease patient registry and Alzheimer's Disease Research Center. Neuropsychological measures shown to have utility in previous studies were included in the analysis. The final multivariate logistic regression model distinguishing DLB from normal controls included Auditory Verbal Learning Test (AVLT) percent retention, Block Design, Trail Making Test-Part A, and Benton Visual Form Discrimination. This model has a sensitivity of 88.6% and specificity of 96.1%. The final multivariate logistic model distinguishing DLB from AD included Trail Making Part A, Boston Naming Test (BNT), AVLT percent retention, and copy of the Rey-Osterrieth Complex Figure. This model had a sensitivity of 83.3% and a specificity of 91.4%. AVLT and BNT had negative coefficients, indicating that lower scores decreased the likelihood of DLB relative to AD. These finding extend prior research suggesting a cognitive profile that can aid in the clinical diagnosis of DLB. Early attention and visual perceptual disturbance suggests DLB, while early impairment in memory and naming suggests AD.

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PubMed2006

Argyrophilic grain disease in demented subjects presenting initially with amnestic mild cognitive impairment.

A previous autopsy study of patients with amnestic-type mild cognitive impairment (MCI) suggested an overrepresentation of argyrophilic grain disease (AGD). We studied 34 patients who had diagnoses of amnestic MCI during progression to dementia and who came to autopsy. Neuropathologic evaluation included routine histochemical and immunohistochemical methods, including a 4-repeat tau-specific marker (ET3). AGD was found in association with a variety of neuropathologic diseases in 18 (53%) cases but was the primary pathologic finding in only one (3%) case. ET3 allowed the detection of AGD in 5 additional cases missed using standard techniques. Cases with AGD were significantly older than those without (mean, 94 vs 84 years; p < 0.004, rank sum test). No significant differences were found between groups for other demographic variables, association of AGD with neuropathologic findings of Alzheimer disease, Lewy body, or cerebrovascular disease, or global measures of cognitive function, although there was a nonsignificant trend towards worsening cognitive status in cases with AGD. AGD is a common pathologic finding in subjects who have been diagnosed with amnestic MCI.

Aged↗
PubMed2006

Mild cognitive impairment should be considered for DSM-V.

Mild cognitive impairment is a topic of great activity from both clinical and research perspectives. It represents a transitional state between the cognitive changes of aging and the earliest clinical manifestations of dementia. We present a case for its inclusion in the Diagnostic and Statistical Manual of Mental Disorders (5th ed; DSM-V) based on clinical, outcome, epidemiological, neuroimaging, and pathophysiological data. The strongest case for inclusion can be made for the amnestic subtype, which is likely a clinical precursor of Alzheimer's disease. Arguments are presented as to why mild cognitive impairment can be considered as an entity distinct from normal aging and from clinically probable Alzheimer's disease and why it deserves consideration as a separate construct. In many respects, mild cognitive impairment fulfills criteria for inclusion more adequately than many other conditions currently codified in DSM-IV. Future research directions to help clarify some of the remaining uncertainties are proposed.

Cognition Disorders↗
PubMed2005

Vitamin E and donepezil for the treatment of mild cognitive impairment.

BACKGROUND: Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. METHODS: In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. RESULTS: A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. CONCLUSIONS: Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo.

Alzheimer Disease↗
PubMed2005

Comparison of different methodological implementations of voxel-based morphometry in neurodegenerative disease.

Voxel-based morphometry (VBM) is a popular method for probing inter-group differences in brain morphology. Variation in the detailed implementation of the algorithm, however, will affect the apparent results of VBM analyses and in turn the inferences drawn about the anatomic expression of specific disease states. We qualitatively assessed group comparisons of 43 normal elderly control subjects and 51 patients with probable Alzheimer's disease, using five different VBM variations. Based on the known pathologic expression of the disease, we evaluated the biological plausibility of each. The use of a custom template and custom tissue class prior probability images (priors) produced inter-group comparison maps with greater biological plausibility than the use of the Montreal Neurological Institute (MNI) template and priors. We present a method for initializing the normalization to a custom template, and conclude that, when incorporated into the VBM processing chain, it yields the most biologically plausible inter-group differences of the five methods presented.

Aged↗
PubMed2005

Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment.

BACKGROUND: Subjects with mild cognitive impairment (MCI) have been shown to have reduced hippocampal volumes relative to normal elderly control subjects. The presence of the apolipoprotein E epsilon4 (APOE*E4) allele has been associated with greater hippocampal atrophy in women than in men with Alzheimer disease. This relationship has not been demonstrated in MCI. OBJECTIVE: To examine the relationship between APOE genotype and hippocampal volume in men and women with MCI. DESIGN: This study evaluated MCI in 193 subjects (86 women and 107 men) participating in a multicenter clinical trial, all of whom underwent magnetic resonance imaging at their baseline visit. We evaluated the association among the number of APOE*E4 alleles, memory performance, and hippocampal volume in men and women with tests of means and multiple linear regressions. RESULTS: Compared with MCI subjects with no APOE*E4 alleles, women with 1 or 2 APOE*E4 alleles were found to have significantly reduced hippocampal volume, whereas men only showed a significant reduction in hippocampal volume when carrying 2 APOE*E4 alleles. Worsening of performance on a delayed word recall task (Alzheimer's Disease Assessment Scale cognitive subscale) showed an identical pattern in association with APOE*E4 allele dose and sex. Furthermore, when controlling for memory performance on delayed word recall, the APOE*E4 effect on hippocampal volumes was attenuated in men, but remained significant in women. CONCLUSION: The APOE*E4 genotype status appears to have a greater deleterious effect on gross hippocampal pathology and memory performance in women than in men.

Aged↗
PubMed2005

Antemortem diagnosis of frontotemporal lobar degeneration.

The objective of this article is to study the accuracy of antemortem clinical diagnoses of frontotemporal lobar degenerations (FTLDs). From brain autopsies performed on subjects enrolled in the Mayo Alzheimer Center between 1991 and 2003, cases with neuropathological diagnoses of FTLD were identified. Neuropathological diagnoses of FTLDs were based on consensus criteria for FTLD. The initial clinical histories, neuropsychological test results, brain imaging studies, and initial clinical diagnoses were reviewed. There were 34 pathological FTLD cases among 433 subjects who underwent autopsy; 29 of these 34 cases were diagnosed as FTLD antemortem based on the sum of clinical, neuropsychological, and imaging features (sensitivity, 85%). The specificity was 99%. Among the 34 cases with pathological FTLD, 27 (79%) had clinical histories diagnostic of an FTLD syndrome, 20 (62%) had neuropsychological profiles consistent with FTLD, 17 (50%) had magnetic resonance scans consistent with FTLD, and 7 of 8 who had functional imaging studies had ones consistent with FTLD. In those with incorrect antemortem diagnoses, three were thought to have Alzheimer's disease, one was considered hard to classify, and one was diagnosed with vascular dementia. The antemortem consensus diagnosis of FTLD was moderately sensitive and very specific. With experienced clinicians and awareness of the unique manifestations of FTLD, accurate antemortem diagnosis was feasible.

Aged↗
PubMed2005

The Alzheimer's disease neuroimaging initiative.

With increasing life expectancy in developed countries, the incidence of Alzheimer's disease (AD) and its socioeconomic impact are growing. Increasing knowledge of the mechanisms of AD facilitates the development of treatment strategies aimed at slowing down or preventing neuronal death. AD treatment trials using clinical outcome measures require long observation times and large patient samples. There is increasing evidence that neuroimaging and cerebrospinal fluid and blood biomarkers may provide information that may reduce sample sizes and observation periods. The Alzheimer's Disease Neuroimaging Initiative will help identify clinical, neuroimaging, and biomarker outcome measures that provide the highest power for measurement of longitudinal changes and for prediction of transitions.

Aged↗
PubMed2005

The effect of tau genotype on clinical features in FTDP-17.

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17.

Adult↗
PubMed2005

Mayo's older African American normative studies: confirmatory factor analysis of a core battery.

Covariance structure analyses of a core neuropsychological test battery consisting of the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and Auditory Verbal Learning Test have previously identified a 5-factor model in a sample of cognitively normal White volunteers from Mayo's Older Americans Normative Studies (MOANS). The present study sought to replicate this factor structure in a sample of 289 cognitively normal, community-dwelling African American elders from Mayo's Older African Americans Normative Studies (MOAANS). The original 5-factor model was tested against 2 alternative 4-factor models and a 6-factor model generated on a substantive basis. Confirmatory factor analysis supported the construct validity of this core battery in older African Americans by replicating the original 5-factor model of Verbal Comprehension, Perceptual Organization, Attention/Concentration, Learning, and Retention as viable in the present sample.

Black or African American↗