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Cognitive reserve and cortical thickness in preclinical Alzheimer's disease.

ABSTRACT: This study examined whether cognitive reserve (CR) alters the relationship between magnetic resonance imaging (MRI) measures of cortical thickness and risk of progression from normal cognition to the onset of clinical symptoms associated with mild cognitive impairment (MCI). The analyses included 232 participants from the BIOCARD study. Participants were cognitively normal and largely middle aged (M age = 56.5) at their baseline MRI scan. After an average of 11.8 years of longitudinal follow-up, 48 have developed clinical symptoms of MCI or dementia (M time from baseline to clinical symptom onset = 7.0 years). Mean thickness was measured over eight 'AD vulnerable' cortical regions, and cognitive reserve was indexed by a composite score consisting of years of education, reading, and vocabulary measures. Using Cox regression models, CR and cortical thickness were each independently associated with risk of clinical symptom onset within 7 years of baseline, suggesting that the neuronal injury occurring proximal to symptom onset has a direct association with clinical outcomes, regardless of CR. In contrast, there was a significant interaction between CR and mean cortical thickness for risk of progression more than 7 years from baseline, suggesting that individuals with high CR are better able to compensate for cortical thinning that is beginning to occur at the very earliest phase of AD.

SUBMITTER: Pettigrew C

PROVIDER: S-EPMC5743433 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Cognitive reserve and cortical thickness in preclinical Alzheimer's disease.

Pettigrew Corinne C Soldan Anja A Zhu Yuxin Y Wang Mei-Cheng MC Brown Timothy T Miller Michael M Albert Marilyn M

Brain imaging and behavior 20170401 2

This study examined whether cognitive reserve (CR) alters the relationship between magnetic resonance imaging (MRI) measures of cortical thickness and risk of progression from normal cognition to the onset of clinical symptoms associated with mild cognitive impairment (MCI). The analyses included 232 participants from the BIOCARD study. Participants were cognitively normal and largely middle aged (M age = 56.5) at their baseline MRI scan. After an average of 11.8 years of longitudinal follow-up, ...[more]

PMID: 27544202

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Project description:Brain atrophy measured by magnetic resonance structural imaging has been proposed as a surrogate marker for the early diagnosis of Alzheimer's disease. Studies on large samples are still required to determine its practical interest at the individual level, especially with regards to the capacity of anatomical magnetic resonance imaging to disentangle the confounding role of the cognitive reserve in the early diagnosis of Alzheimer's disease. One hundred and thirty healthy controls, 122 subjects with mild cognitive impairment of the amnestic type and 130 Alzheimer's disease patients were included from the ADNI database and followed up for 24 months. After 24 months, 72 amnestic mild cognitive impairment had converted to Alzheimer's disease (referred to as progressive mild cognitive impairment, as opposed to stable mild cognitive impairment). For each subject, cortical thickness was measured on the baseline magnetic resonance imaging volume. The resulting cortical thickness map was parcellated into 22 regions and a normalized thickness index was computed using the subset of regions (right medial temporal, left lateral temporal, right posterior cingulate) that optimally distinguished stable mild cognitive impairment from progressive mild cognitive impairment. We tested the ability of baseline normalized thickness index to predict evolution from amnestic mild cognitive impairment to Alzheimer's disease and compared it to the predictive values of the main cognitive scores at baseline. In addition, we studied the relationship between the normalized thickness index, the education level and the timeline of conversion to Alzheimer's disease. Normalized thickness index at baseline differed significantly among all the four diagnosis groups (P < 0.001) and correctly distinguished Alzheimer's disease patients from healthy controls with an 85% cross-validated accuracy. Normalized thickness index also correctly predicted evolution to Alzheimer's disease for 76% of amnestic mild cognitive impairment subjects after cross-validation, thus showing an advantage over cognitive scores (range 63-72%). Moreover, progressive mild cognitive impairment subjects, who converted later than 1 year after baseline, showed a significantly higher education level than those who converted earlier than 1 year after baseline. Using a normalized thickness index-based criterion may help with early diagnosis of Alzheimer's disease at the individual level, especially for highly educated subjects, up to 24 months before clinical criteria for Alzheimer's disease diagnosis are met.

Project description:The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer's disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury via cerebral spinal fluid t-tau, brain amyloid-? load via cerebral spinal fluid amyloid-?1-42 and vascular disease via white matter hyperintensities on T2/proton density magnetic resonance images. We included 109 cognitively normal subjects, 192 amnestic patients with mild cognitive impairment and 98 patients with Alzheimer's disease, from the Alzheimer's Disease Neuroimaging Initiative study, who had undergone baseline lumbar puncture and magnetic resonance imaging. We combined patients with mild cognitive impairment and Alzheimer's disease in a group labelled 'cognitively impaired' subjects. Structural Abnormality Index scores, which reflect the degree of Alzheimer's disease-like anatomic features on magnetic resonance images, were computed for each subject. We assessed Alzheimer's Disease Assessment Scale (cognitive behaviour section) and mini-mental state examination scores as measures of general cognition and Auditory-Verbal Learning Test delayed recall, Boston naming and Trails B scores as measures of specific domains in both groups of subjects. The number of errors on the American National Adult Reading Test was used as a measure of environmental enrichment provided by educational and occupational attainment, a component of cognitive reserve. We found that in cognitively normal subjects, none of the biomarkers correlated with the measures of cognition, whereas American National Adult Reading Test scores were significantly correlated with Boston naming and mini-mental state examination results. In cognitively impaired subjects, the American National Adult Reading Test and all biomarkers of neuronal pathology and amyloid load were independently correlated with all cognitive measures. Exceptions to this general conclusion were absence of correlation between cerebral spinal fluid amyloid-?1-42 and Boston naming and Trails B. In contrast, white matter hyperintensities were only correlated with Boston naming and Trails B results in the cognitively impaired. When all subjects were included in a flexible ordinal regression model that allowed for non-linear effects and interactions, we found that the American National Adult Reading Test had an independent additive association such that better performance was associated with better cognitive performance across the biomarker distribution. Our main conclusions included: (i) that in cognitively normal subjects, the variability in cognitive performance is explained partly by the American National Adult Reading Test and not by biomarkers of Alzheimer's disease pathology; (ii) in cognitively impaired subjects, the American National Adult Reading Test, biomarkers of neuronal pathology (structural magnetic resonance imaging and cerebral spinal fluid t-tau) and amyloid load (cerebral spinal fluid amyloid-?1-42) all independently explain variability in general cognitive performance; and (iii) that the association between cognition and the American National Adult Reading Test was found to be additive rather than to interact with biomarkers of Alzheimer's disease pathology.

Dataset Information

Cognitive reserve and cortical thickness in preclinical Alzheimer's disease.

Publications

Cognitive reserve and cortical thickness in preclinical Alzheimer's disease.

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