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Artificially low mild cognitive impairment to normal reversion rate in the Alzheimer's Disease Neuroimaging Initiative.

ABSTRACT: INTRODUCTION:We examined reasons for low mild cognitive impairment (MCI)-to-cognitively normal (CN) reversion rates in the Alzheimer's Disease Neuroimaging Initiative (ADNI). METHODS:CN and MCI participants were identified as remaining stable, progressing, or reverting at 1-year of follow-up (Year 1). Application of ADNI's MCI criteria at Year 1 in addition to Alzheimer's disease biomarkers by group were examined. RESULTS:The MCI-to-CN reversion rate was 3.0%. When specific components were examined, 22.5% of stable MCI participants had normal memory performance at Year 1 and their Alzheimer's disease biomarkers were consistent with the stable CN group. At Year 1, when all MCI criteria were not met, the more subjective Clinical Dementia Rating rather than objective memory measure appeared to drive continuation of the MCI diagnosis. DISCUSSION:Results demonstrate an artificially low 1-year MCI-to-CN reversion rate in ADNI-diagnosed participants. If the Logical Memory cutoffs had been consistently applied, the reversion rate would have been at least 21.8%.

SUBMITTER: Thomas KR

PROVIDER: S-EPMC6461519 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Artificially low mild cognitive impairment to normal reversion rate in the Alzheimer's Disease Neuroimaging Initiative.

Thomas Kelsey R KR Eppig Joel S JS Weigand Alexandra J AJ Edmonds Emily C EC Wong Christina G CG Jak Amy J AJ Delano-Wood Lisa L Galasko Douglas R DR Salmon David P DP Edland Steven D SD Bondi Mark W MW

Alzheimer's & dementia : the journal of the Alzheimer's Association 20190111 4

<h4>Introduction</h4>We examined reasons for low mild cognitive impairment (MCI)-to-cognitively normal (CN) reversion rates in the Alzheimer's Disease Neuroimaging Initiative (ADNI).<h4>Methods</h4>CN and MCI participants were identified as remaining stable, progressing, or reverting at 1-year of follow-up (Year 1). Application of ADNI's MCI criteria at Year 1 in addition to Alzheimer's disease biomarkers by group were examined.<h4>Results</h4>The MCI-to-CN reversion rate was 3.0%. When specific ...[more]

PMID: 30610833

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Project description:IntroductionAnalyses of off-label use of acetylcholinesterase inhibitors (AChEIs) in mild cognitive impairment (MCI) has produced mixed results. Post hoc analyses of observational cohorts, such as the Alzheimer's Disease Neuroimaging Initiative (ADNI), have reported deleterious effects in AChEI-treated subjects (AChEI+). Here, we used neuroimaging biomarkers to determine whether AChEI+ subjects had a greater rate of neurodegeneration than untreated (AChEI-) subjects while accounting for baseline differences.MethodsWe selected 121 ADNI MCI AChEI+ subjects and 151 AChEI- subjects with a magnetic resonance imaging (MRI) scan; 82 AChEI+ and 110 AChEI- also had a fluorodeoxyglucose (FDG) scan. A subset (83 AChEI+ and 98 AChEI-) had cerebrospinal fluid (CSF) or amyloid positron emission tomography (PET) assessment for amyloid positivity. Linear regression models were used to compare the effect of treatment on changes in Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes scores. We used standard regression in SPM (for baseline) and the SPM toolbox sandwich estimator, SwE (for longitudinal) for comparisons of AChEI+ and AChEI- FDG PET and MRI data.ResultsAt baseline, the AChEI+ group had significantly reduced cortical gray matter density (GMD) and more hypometabolism than AChEI- subjects. The greater rate of atrophy and hypometabolic changes over time in AChEI+ compared to AChEI- subjects did not survive correction for baseline differences. AChEI+ participants were more likely to be amyloid-positive and have lower GMD and FDG standardized uptake value ratio than AChEI- at baseline. AChEI+ subjects showed greater atrophy over time, which remained significant after controlling for amyloid status.DiscussionOur data suggest that the observed differences in rates of cognitive decline, atrophy, and hypometabolism are likely the result of significant baseline differences between the groups. Furthermore, the data indicate no treatment effect of AChEI (positive of negative), rather that physicians prescribe AChEI to subjects who present with more severe clinical impairment. This alone may account for the negative effect seen previously in the ADNI population of AChEI use among MCI subjects.

Project description:IntroductionMild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition.MethodsOur analyses considered 223 participants (48.9% male) aged 71-89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors.ResultsThere were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p?=?0.011), a moderately or severely impaired cognitive domain (p?=?0.002 and p?=?0.006), or an informant-based memory complaint (p?=?0.031). Reversion was also less likely for participants with arthritis (p?=?0.037), but more likely for participants with higher complex mental activity (p?=?0.003), greater openness to experience (p?=?0.041), better vision (p?=?0.014), better smelling ability (p?=?0.040), or larger combined volume of the left hippocampus and left amygdala (p<0.040). Reversion was also associated with a larger drop in diastolic blood pressure between baseline and follow-up (p?=?0.026).DiscussionNumerous factors are associated with reversion from MCI to normal cognition. Assessing these factors could facilitate more accurate prognosis of individuals with MCI. Participation in cognitively enriching activities and efforts to lower blood pressure might promote reversion.

Project description:IntroductionIt is important to study apathy in Alzheimer's disease (AD) to better understand its underlying neurobiology and develop effective interventions. In the current study, we sought to examine the relationships between longitudinal apathy and regional tau burden in cognitively impaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.MethodsThree hundred and nineteen ADNI participants with mild cognitive impairment (MCI) or AD dementia underwent flortaucipir (FTP) tau positron emission tomography (PET) imaging and clinical assessment with the Neuropsychiatric Inventory (NPI) annually. Longitudinal NPI Apathy (NPI-A) scores were examined in relation to baseline tau PET signal in three a priori selected regions implicated in AD and AD-related apathy (supramarginal gyrus, entorhinal cortex [EC] and rostral anterior cingulate cortex [rACC]). Secondary models were adjusted for global cognition (Mini-Mental State Examination score) and cortical amyloid (florbetapir PET).ResultsHigher baseline supramarginal gyrus and EC tau burden were each significantly associated with greater NPI-A over time, while rACC tau was associated with higher NPI-A but did not predict its trajectory over time. These results were retained for supramarginal and EC tau after adjusting models for global cognition and cortical amyloid.DiscussionOur findings suggest that baseline in vivo tau burden in parietal and temporal brain regions affected in AD, and less so in a medial frontal region involved in motivational control, is associated with increasing apathy over time in older adults with MCI and AD dementia. Future work studying emergent apathy in relation to not only core AD pathology but also circuit level dysfunction may provide additional insight into the neurobiology of apathy in AD and opportunities for intervention.HighlightsTau (Flortaucipir PET) in regions implicated in AD was associated with increasing apathy over timeCortical amyloid was also found to be a robust predictor of the trajectory of apathyEvidence of synergy between regional tau and amyloid in overall higher levels of apathy.

Project description:PurposeTo detect changes in brain lateralization in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) using resting-state functional magnetic resonance imaging (fMRI).Materials and methodsData from 61 well-matched right-handed subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative, including 19 healthy controls (HCs), 25 patients with MCI, and 17 patients with AD. First, we divided 256 pairs of seed regions from each hemisphere covering the entire cerebral gray matter. Then, we used the intrinsic laterality index (iLI) approach to quantify the functional laterality using fMRI. One-way ANOVA was employed to estimate the differences in iLI among the three groups. The sum, number and mean value of the iLI were calculated within the thresholds of 0?<?|iLI|?<?0.2, 0.2???|iLI|?<?0.4, 0.4???|iLI|?<?0.8, and |iLI|???0.8, to explore the changes in the lateralization of resting-state brain function in patients with MCI and AD.ResultsOne-way ANOVA revealed that the iLIs of the three groups were significantly different. The HCs showed a significant leftward interhemispheric difference within |iLI|???0.8. Compared with the HCs, the patients with MCI manifested a distinct abnormal rightward interhemispheric asymmetry, mainly within the thresholds of 0.2???|iLI|?<?0.4 and 0.4???|iLI|?<?0.8; in the patients with AD, the normal leftward lateralization that was observed in the HCs disappeared, and an abnormal rightward laterality was expressed within 0.4???|iLI|?<?0.8. By directly comparing the patients with MCI with the patients with AD, an exclusive abnormal rightward laterality was observed in the patients with MCI within the 0.2???|iLI|?<?0.4 threshold, and the normal leftward asymmetry vanished in the patients with AD within the |iLI|???0.8 threshold.ConclusionGlobal brain lateralization was different among three groups. The abnormal rightward dominance observed in the patients with MCI and AD may indicate that these patients use additional brain resources to compensate for the loss of cognitive function, and the observed disappearance of the leftward laterality in the patients with AD was likely associated with the damage in the left hemisphere. The observed disappearance of the rightward asymmetry in the patients with AD using the 0.2???|iLI|?<?0.4 threshold was likely a sign of decompensation. Our study provides new insights that may improve our understanding of MCI and AD.

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Artificially low mild cognitive impairment to normal reversion rate in the Alzheimer's Disease Neuroimaging Initiative.

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Artificially low mild cognitive impairment to normal reversion rate in the Alzheimer's Disease Neuroimaging Initiative.

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