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Normative neuropsychological data are essential for interpretation of test performance in the context of demographic factors. The Mayo Normative Studies (MNS) aim to provide updated normative data for neuropsychological measures administered in the Mayo Clinic Study of Aging (MCSA), a population-based study of aging that randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. We examined demographic effects on neuropsychological measures and validated the regression-based norms in comparison to existing normative data developed in a similar sample.
The MNS includes cognitively unimpaired adults ≥30 years of age (n = 4,428) participating in the MCSA. Multivariable linear regressions were used to determine demographic effects on test performance. Regression-based normative formulas were developed by first converting raw scores to normalized scaled scores and then regressing on age, age2, sex, and education. Total and sex-stratified base rates of low scores (T < 40) were examined in an older adult validation sample and compared with Mayo’s Older Americans Normative Studies (MOANS) norms.
Independent linear regressions revealed variable patterns of linear and/or quadratic effects of age (r2 = 6–27% variance explained), sex (0–13%), and education (2–10%) across measures. MNS norms improved base rates of low performance in the older adult validation sample overall and in sex-specific patterns relative to MOANS.
Our results demonstrate the need for updated norms that consider complex demographic associations on test performance and that specifically exclude participants with mild cognitive impairment from the normative sample.
The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey’s Auditory Verbal Learning Test (AVLT).
Participants (N = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (amyloid PET positive, A+, n = 125) or not (A-, n = 228), and those with biological AD (amyloid and tau PET positive, A+T+, n = 55) vs no evidence of AD pathology (A−T−, n = 195). Analyses were repeated among CU participants only.
The SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p’s > .05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education, and sex, including when limited to CU participants. Medium (A− vs A+) to large (A−T− vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups.
Remotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.
Rey’s Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.
This study advances the Mayo’s Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30–91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided.
From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8–10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex.
Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
Functional magnetic resonance imaging (fMRI) shows changes in multiple regions in amnestic mild cognitive impairment (aMCI). The concept of MCI recently evolved to include nonamnestic syndromes, so little is known about fMRI changes in these individuals. This study investigated activation during visual complex scene encoding and recognition in 29 cognitively normal (CN) elderly, 19 individuals with aMCI, and 12 individuals with nonamnestic MCI (naMCI). During encoding, CN activated an extensive network that included bilateral occipital–parietal–temporal cortex; precuneus; posterior cingulate; thalamus; insula; and medial, anterior, and lateral frontal regions. Amnestic MCI activated an anatomic subset of these regions. Non-amnestic MCI activated an even smaller anatomic subset. During recognition, CN activated the same regions observed during encoding except the precuneus. Both MCI groups again activated a subset of the regions activated by CN. During encoding, CN had greater activation than aMCI and naMCI in bilateral temporoparietal and frontal regions. During recognition, CN had greater activation than aMCI in predominantly temporoparietal regions bilaterally, while CN had greater activation than naMCI in larger areas involving bilateral temporoparietal and frontal regions. The diminished parietal and frontal activation in naMCI may reflect compromised ability to perform nonmemory (i.e., attention/executive, visuospatial function) components of the task. (JINS, 2009, 15, 372–382.)
To assess the cross-sectional association of dietary and supplemental antioxidant (carotenoids, vitamins C and E) intake with cognitive function in 12 187 individuals, aged 48–67 years, participating in the Atherosclerosis Risk in Communities (ARIC) Study.
Dietary intake of antioxidant vitamins, as assessed by a food frequency questionnaire, and use of supplements were analysed in relation to the results of three cognitive tests, the delayed word recall test, the Wechsler adult intelligence scale, revised (WAIS-R) digit symbol subtest and the word fluency test.
After adjustment for covariates previously found to be associated with cognition in this sample, we found no consistent associations between dietary antioxidant vitamin intake or supplement use and any of the cognitive tests.
This study suggests little, if any, association between antioxidant vitamin intake and better cognitive function in middle-aged adults.
Mild cognitive impairment (MCI) has become a major issue in the fields of geriatrics, behavioral neurology and geriatric psychiatry. While some have embraced the construct as a step forward in understanding the prodromal stages of dementing disorders, others have assailed the concept as counterproductive and distracting. Perhaps this is appropriate, since any new proposal for the clinical characterization of impaired subjects should undergo strict scrutiny.
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, χ2 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.
The aim of this study was to examine the associations of
apolipoprotein E (APOE) genotype, metabolic changes in the
posterior cingulate detected by 1H magnetic resonance
spectroscopy (MRS), and neuropsychologic measures of memory and
cognition both in normally aging elderly, and in patients with
mild cognitive impairment (MCI) and AD. We studied 67 controls,
18 MCI and 33 AD patients. We used the Dementia Rating Scale total
score (DRSTOT) as a measure of general cognitive function and the
total learning from the Auditory Verbal Learning Test (AVTOT) as a
measure of memory performance. No differences were noted on
1H-MRS metabolite ratios or cognitive measures across
APOE genotype within control and patient groups. In controls, age
was a significant predictor of both cognitive test scores, and NAA/Cr
was a univariate associate of DRSTOT. All 3 1H-MRS
metabolite ratios, N-acetylaspartate (NAA)/creatine (Cr),
myoinositol (MI)/Cr, and NAA/MI, were univariate associates
of AVTOT and DRSTOT scores in the combined MCI and AD group.
In stepwise regression analyses in the combined patient group
only NAA/MI entered the models. These data suggest NAA/Cr could
be a modest predictor of general cognitive function in both
healthy elderly and impaired patients, while MI/Cr is a more
specific marker for neuropsychologic dysfunction associated
with neurodegenerative disease. Among 1H-MRS
measurements, the NAA/MI ratio maybe the most efficient predictor
of memory and cognitive function in patients with MCI and AD.
(JINS, 2002, 8, 934–942.)
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