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Robert J Ivnik

Publications and source records attributed to Robert J Ivnik.

At least 19 recordsLinked to original sources
PubMed2006

Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease.

Magnetic resonance (MR)-based volume measurements of atrophy are potential markers of disease progression in patients with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Longitudinal changes in (1)H MR spectroscopy ((1)H MRS) metabolite markers have not been characterized in MCI subjects. Our objective was to determine the longitudinal (1)H MRS metabolite changes in patients with MCI, and AD, and to compare (1)H MRS metabolite ratios and ventricular volumes in tracking clinical disease progression in AD. The neuronal integrity marker N-acetylaspartate/creatine ratio declined in MCI and AD patients compared to cognitively normal elderly. The change in (1)H MRS metabolite ratios correlated with clinical progression about as strongly as the rate of ventricular expansion, suggesting that (1)H MRS metabolite ratios may be useful markers for the progression of AD. Choline/creatine ratio declined in stable MCI, compared to converter MCI patients and cognitively normal elderly, which may be related to a compensatory mechanism in MCI patients who did not to progress to AD.

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PubMed2006

Effects of ApoE genotype and mild cognitive impairment on implicit learning.

The goals were to investigate implicit learning in mild cognitive impairment (MCI), and to determine the relations of implicit learning systems to apolipoprotein E (ApoE) genotype in healthy controls. Elderly controls grouped by ApoE status (ApoE-e4 allele carriers versus ApoE-e4 allele non-carriers) and MCI patients participated in the study. Individuals in all three groups completed both contextual cueing and serial reaction time (SRT) tasks. In the former, people learn to use repeated spatial configurations to facilitate search for a target, whereas in the latter, they learn to use subtle sequence regularities to respond more quickly and accurately to a series of events. Results revealed that healthy elderly individuals carrying the ApoE-e4 allele showed contextual cueing deficits compared to those who did not carry the ApoE-e4 allele. Further, elderly controls carrying the ApoE-e4 allele revealed similar amounts of contextual cueing as the MCI group, while the non-carriers performed better. Sequence learning, by contrast, was uninfluenced by either MCI or by ApoE genotype in healthy controls. This study provides further support for the medial temporal lobe dysfunction and relative integrity of fronto-striatal systems in MCI, and indicates the influence of ApoE genotype on implicit learning even in healthy older individuals without cognitive impairment.

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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.

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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.

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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.

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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

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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PubMed2005

Cognitive function after radiotherapy for supratentorial low-grade glioma: a North Central Cancer Treatment Group prospective study.

PURPOSE: To evaluate the effects of cranial radiotherapy (RT) on cognitive function in patients with supratentorial low-grade glioma. METHODS AND MATERIALS: Twenty adult patients with supratentorial low-grade glioma were treated with 50.4 Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were evaluated with an extensive battery of psychometric tests at baseline (before RT) and at approximately 18-month intervals for as long as 5 years after completing RT. To allow patients to serve as their own controls, cognitive performance was evaluated as change in scores over time. All patients underwent at least two evaluations. RESULTS: Baseline test scores were below average compared with age-specific norms. At the second evaluation, the groups' mean test scores were higher than their initial performances on all psychometric measures, although the improvement was not statistically significant. No changes in cognitive performance were seen during the evaluation period when test scores were analyzed by age, treatment, tumor location, tumor type, or extent of resection. CONCLUSIONS: Cognitive function was stable after RT in these patients evaluated prospectively during 3 years of follow-up. Slight improvements in some cognitive areas are consistent with practice effects attributable to increased familiarity with test procedures and content.

Adolescent↗
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.

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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↗
PubMed2005

Mayo's Older African Americans Normative Studies: normative data for commonly used clinical neuropsychological measures.

This report describes the methodology and sample characteristics of Mayo's Older African Americans Normative Studies (MOAANS). These studies reflect a multidisciplinary, collaborative effort by investigators at Mayo Clinic to provide age-appropriate normative data for African American elders on commonly used neuropsychological tests. A sample of 309 community-dwelling individuals over age 55 contributed to the MOAANS sample. Norms were calculated for midpoint age groups, based on percentile scores derived from cumulative frequencies of raw test scores. Demographic, medical, and sociocultural data were also collected, and are summarized to assist clinicians in making determinations regarding the appropriateness of these norms for individual patients. In most cases, the use of MOAANS norms should improve diagnostic accuracy in dementia evaluations of African American elders.

Black or African American↗
PubMed2005

A brief report on WAIS-R normative data collection in Mayo's Older African Americans Normative Studies.

Historically, neuropsychological measures such as the Wechsler Adult Intelligence Scale-Revised (WAIS-R) have yielded unacceptably high rates of misdiagnosis of impairment among cognitively normal African Americans, primarily due to poor test specificity and inadequate representation of ethnic minorities in the normative sample. In this report, we briefly review these issues and describe efforts by investigators in Mayo's Older African Americans Normative Studies (MOAANS) to develop more appropriate norms for African American elders on the WAIS-R. During MOAANS data collection, the third edition of the WAIS (WAIS-III) was introduced with updated representation of ethnic minorities in the normative database. More recently, specific demographic corrections for African Americans have been derived for WAIS-III subtest scores and indices. As such, WAIS-R normative estimates are not presented here. Interested readers who wish to obtain a full set of MOAANS WAIS-R norms, however, are invited to contact the authors for these data.

Black or African American↗
PubMed2005

Mayo's Older African Americans Normative Studies: WMS-R norms for African American elders.

Norms for African American elders on the Wechsler Memory Scale-Revised (WMS-R) were derived from a sample of 309 community-dwelling individuals participating in Mayo's Older African Americans Normative Studies (MOAANS). Normative estimates are provided for traditional WMS-R subtest scores and for supplemental procedures to evaluate forgetting rates and recognition memory. Tables are provided to convert raw WMS-R subtest and supplemental scores to age-corrected scaled scores. These may be further adjusted for years of education, if desired, by applying regression-based corrections. We anticipate that these data will enhance the diagnostic utility and clinical interpretation of WMS-R performance in older African Americans.

Black or African American↗
PubMed2005

Mayo's Older African American Normative Studies: Auditory Verbal Learning Test norms for African American elders.

The Auditory Verbal Learning Test (AVLT) is frequently used in clinical practice to assess for memory dysfunction in the elderly. As part of the Mayo Older African Americans Normative Studies (MOAANS), we provide age and education adjusted normative data for the AVLT. The sample consists of 306 self-identified African Americans who are cognitively normal, community-dwelling and ranging in age from 56 through 94. Additional summary indices are included in the normative data, including learning efficiency, delayed recall, percent retention, and an index representing recognition memory corrected for false-positive identifications. Given the importance of using a normative reference sample that closely represents the population of interest, the current norms should provide clinically useful data for evaluating African American elders, especially those who were educated in the southern United States.

Adult↗
PubMed2005

Mayo's Older African American Normative Studies: norms for the Mattis Dementia Rating Scale.

Normative data are presented for older African Americans on the Mattis Dementia Rating Scale (DRS). These data were collected as part of Mayo's Older African Americans Normative Studies (MOAANS) in an effort to develop age-appropriate norms for African Americans elders on commonly used measures in neuropsychological assessment. In this study, the DRS was administered to 307 MOAANS participants ranging in age from 56 to 94 years. Age-corrected subtest and total scores were derived based on percentile ranks from actual frequency distributions across seven age ranges. Also presented is a regression-based computational formula that may be applied to the age-corrected DRS total score to further correct for years of education. These norms should help improve interpretation of DRS performance in African Americans and allow for greater diagnostic accuracy in patients with early cognitive decline.

Black or African American↗
PubMed2005

Mayo's Older African Americans Normative Studies: norms for Boston Naming Test, Controlled Oral Word Association, Category Fluency, Animal Naming, Token Test, WRAT-3 Reading, Trail Making Test, Stroop Test, and Judgment of Line Orientation.

Normative data for older African Americans are presented for several clinical neuropsychological measures, including Boston Naming Test, Controlled Oral Word Association, Category Fluency, Token Test, WRAT-3 Reading, Trail Making Test, Stroop Color and Word Test, and Judgment of Line Orientation. Age-adjusted norms were derived from a sample of 309 cognitively normal, community-dwelling individuals, aged 56 through 94, participating in Mayo's Older African Americans Normative Studies (MOAANS). Years of education were modelled on age-scaled scores to derive regression Equations that may be applied for further demographic correction. These data should enhance interpretation of individual test performances and facilitate analysis of neuropsychological profile patterns in older African American patients who present for dementia evaluations.

Black or African American↗
PubMed2004

De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI).

BACKGROUND: There is inadequate information regarding the neuropsychiatric aspect of Mild Cognitive Impairment (MCI). OBJECTIVE: To determine the neuropsychiatric profile of MCI, and compare this with normal controls and patients with mild Alzheimer's Disease (AD). DESIGN: Cross-sectional assessment of psychiatric symptoms in subjects that are enrolled in Mayo Clinic's longitudinal study of normal aging, MCI and dementia. METHODS AND PARTICIPANTS: The Neuropsychiatric Inventory (NPI) was administered to normal control subjects, MCI subjects and patients with early AD. Individual NPI domain scores and total NPI scores were compared among the three groups after controlling for age, educational status, Dementia Rating Scale (DRS) and Mini-Mental State Examination (MMSE) scores. Statistical analysis was performed by utilizing ANOVA, chi2 and Fisher's exact test. RESULTS: Data were analyzed on 514 normal controls, 54 MCI subjects, and 87 subjects with mild AD (CDR of 0.5 or 1); females consisted of 60.3%, 53.7% and 57.5%; and, the average ages (SD) were 77.8 (1.95), 79 (4.6), 80.5 (14.6) respectively. ANOVA pair-wise comparison revealed that both MMSE and DRS differences among the three groups were significantly different at (p = 0.05). The total NPI scores were significantly different (p =0.0001, F = 107.93) among the three groups using ANOVA. Pair-wise comparison of individual behavioral domain of NPI showed statistically significant differences between MCI and normals; and MCI and AD (p = 0.001). Group differences on NPI remained after controlling for age and education at p = 0.0375 and p = 0.0050 respectively. CONCLUSION: The neuropsychiatric pattern is reminiscent of the clinical, neuroimaging and neuropsychological profile of MCI. It gives further credence to the view that MCI is indeed the gray zone, with overlap on both ends of the pole.

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