Dataset Information

Heterogeneity of Regional Brain Atrophy Patterns Associated with Distinct Progression Rates in Alzheimer's Disease.

ABSTRACT: We aimed to identify and characterize subtypes of Alzheimer's disease (AD) exhibiting different patterns of regional brain atrophy on MRI using age- and gender-specific norms of regional brain volumes. AD subjects included in the Alzheimer's Disease Neuroimaging Initiative study were classified into subtypes based on standardized values (Z-scores) of hippocampal and regional cortical volumes on MRI with reference to age- and gender-specific norms obtained from 222 cognitively normal (CN) subjects. Baseline and longitudinal changes of clinical characteristics over 2 years were compared across subtypes. Whole-brain-level gray matter (GM) atrophy pattern using voxel-based morphometry (VBM) and cerebrospinal fluid (CSF) biomarkers of the subtypes were also investigated. Of 163 AD subjects, 58.9% were classified as the "both impaired" subtype with the typical hippocampal and cortical atrophy pattern, whereas 41.1% were classified as the subtypes with atypical atrophy patterns: "hippocampal atrophy only" (19.0%), "cortical atrophy only" (11.7%), and "both spared" (10.4%). Voxel-based morphometric analysis demonstrated whole-brain-level differences in overall GM atrophy across the subtypes. These subtypes showed different progression rates over 2 years; and all subtypes had significantly lower CSF amyloid-? 1-42 levels compared to CN. In conclusion, we identified four AD subtypes exhibiting heterogeneous atrophy patterns on MRI with different progression rates after controlling the effects of aging and gender on atrophy with normative information. CSF biomarker analysis suggests the presence of A? neuropathology irrespective of subtypes. Such heterogeneity of MRI-based neuronal injury biomarker and related heterogeneous progression patterns should be considered in clinical trials and practice with AD patients.

SUBMITTER: Byun MS

PROVIDER: S-EPMC4664412 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Heterogeneity of Regional Brain Atrophy Patterns Associated with Distinct Progression Rates in Alzheimer's Disease.

Byun Min Soo MS Kim Song E SE Park Jinsick J Yi Dahyun D Choe Young Min YM Sohn Bo Kyung BK Choi Hyo Jung HJ Baek Hyewon H Han Ji Young JY Woo Jong Inn JI Lee Dong Young DY

PloS one 20151130 11

We aimed to identify and characterize subtypes of Alzheimer's disease (AD) exhibiting different patterns of regional brain atrophy on MRI using age- and gender-specific norms of regional brain volumes. AD subjects included in the Alzheimer's Disease Neuroimaging Initiative study were classified into subtypes based on standardized values (Z-scores) of hippocampal and regional cortical volumes on MRI with reference to age- and gender-specific norms obtained from 222 cognitively normal (CN) subject ...[more]

PMID: 26618360

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Project description:Introduction: It has been shown that Alzheimer's disease (AD) is accompanied by marked structural brain changes that can be detected several years before clinical diagnosis via structural magnetic resonance (MR) imaging. In this study, we developed a structural MR-based biomarker for in vivo detection of AD using a supervised machine learning approach. Based on an individual's pattern of brain atrophy a continuous AD score is assigned which measures the similarity with brain atrophy patterns seen in clinical cases of AD. Methods: The underlying statistical model was trained with MR scans of patients and healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1 screening). Validation was performed within ADNI-1 and in an independent patient sample from the Open Access Series of Imaging Studies (OASIS-1). In addition, our analyses included data from a large general population sample of the Study of Health in Pomerania (SHIP-Trend). Results: Based on the proposed AD score we were able to differentiate patients from healthy controls in ADNI-1 and OASIS-1 with an accuracy of 89% (AUC = 95%) and 87% (AUC = 93%), respectively. Moreover, we found the AD score to be significantly associated with cognitive functioning as assessed by the Mini-Mental State Examination in the OASIS-1 sample after correcting for diagnosis, age, sex, age·sex, and total intracranial volume (Cohen's f2 = 0.13). Additional analyses showed that the prediction accuracy of AD status based on both the AD score and the MMSE score is significantly higher than when using just one of them. In SHIP-Trend we found the AD score to be weakly but significantly associated with a test of verbal memory consisting of an immediate and a delayed word list recall (again after correcting for age, sex, age·sex, and total intracranial volume, Cohen's f2 = 0.009). This association was mainly driven by the immediate recall performance. Discussion: In summary, our proposed biomarker well differentiated between patients and healthy controls in an independent test sample. It was associated with measures of cognitive functioning both in a patient sample and a general population sample. Our approach might be useful for defining robust MR-based biomarkers for other neurodegenerative diseases, too.

Project description:BackgroundCerebrospinal fluid (CSF) ?-synuclein is reduced in synucleinopathies, including dementia with Lewy bodies, and some studies have found increased CSF ?-synuclein in Alzheimer's disease (AD). No study has explored effects of CSF ?-synuclein on brain atrophy. Here we tested if baseline CSF ?-synuclein affects brain atrophy rates and if these effects vary across brain regions, and across the cognitive spectrum from healthy elders (NL), to patients with mild cognitive impairment (MCI) and AD.MethodsBaseline CSF ?-synuclein measurements and longitudinal structural brain magnetic resonance imaging was performed in 74 NL, 118 MCI patients and 55 AD patients. Effects of baseline CSF ?-synuclein on regional atrophy rates were tested in 1) four pre-hoc defined regions possibly associated with Lewy body and/or AD pathology (amygdala, caudate, hippocampus, brainstem), and 2) all available regions of interest. Differences across diagnoses were tested by assessing the interaction of CSF ?-synuclein and diagnosis (testing NL versus MCI, and NL versus AD).ResultsThe effects of CSF ?-synuclein on longitudinal atrophy rates were not significant after correction for multiple comparisons. There were tendencies for effects in AD in caudate (higher atrophy rates in subjects with higher CSF ?-synuclein, P=0.046) and brainstem (higher atrophy rates in subjects with lower CSF ?-synuclein, P=0.063). CSF ?-synuclein had significantly different effects on atrophy rates in NL and AD in brainstem (P=0.037) and caudate (P=0.006).DiscussionWith the possible exception of caudate and brainstem, the overall weak effects of CSF ?-synuclein on atrophy rates in NL, MCI and AD argues against CSF ?-synuclein as a biomarker related to longitudinal brain atrophy in these diagnostic groups. Any effects of CSF ?-synuclein may be attenuated by possible simultaneous occurrence of AD-related neuronal injury and concomitant Lewy body pathology, which may elevate and reduce CSF ?-synuclein levels, respectively.

Dataset Information

Heterogeneity of Regional Brain Atrophy Patterns Associated with Distinct Progression Rates in Alzheimer's Disease.

Publications

Heterogeneity of Regional Brain Atrophy Patterns Associated with Distinct Progression Rates in Alzheimer's Disease.

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