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

Byun MS, Kim SE, Park J, Yi D, Choe YM, Sohn BK, Choi HJ, Baek H, Han JY, Woo JI, Lee DY, Alzheimer’s Disease Neuroimaging Initiati - PLoS ONE (2015)

Bottom Line: Baseline and longitudinal changes of clinical characteristics over 2 years were compared across subtypes.These subtypes showed different progression rates over 2 years; and all subtypes had significantly lower CSF amyloid-β 1-42 levels compared to CN.CSF biomarker analysis suggests the presence of Aβ neuropathology irrespective of subtypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

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-β 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 Aβ 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.

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Related in: MedlinePlus

Longitudinal changes of cognitive function over 2 years across AD subtypes.Baseline, 1-year, and 2-year follow-up data on (A) MMSE indicating global cognition, (B) ADNI-Mem indicating memory function and (C) ADNI-EF indicating executive function are plotted, with means and standard errors. AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; MMSE; Mini-mental state examination; ADNI-Mem, composite score of memory function; ADNI-EF, composite score of executive function.
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pone.0142756.g002: Longitudinal changes of cognitive function over 2 years across AD subtypes.Baseline, 1-year, and 2-year follow-up data on (A) MMSE indicating global cognition, (B) ADNI-Mem indicating memory function and (C) ADNI-EF indicating executive function are plotted, with means and standard errors. AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; MMSE; Mini-mental state examination; ADNI-Mem, composite score of memory function; ADNI-EF, composite score of executive function.

Mentions: Upon LMM analyses of neuropsychological measures over 2 years in AD subjects, the subtype-by-time interaction, the subtype and time effects were all significant (S2 Table). Compared to the BI, the BS showed the slowest progression rates and the HA also showed relatively slow progression. In contrast, the CA showed the most rapid rates of cognitive decline over 2 years among the subtypes (Fig 2, S3 Table).


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

Byun MS, Kim SE, Park J, Yi D, Choe YM, Sohn BK, Choi HJ, Baek H, Han JY, Woo JI, Lee DY, Alzheimer’s Disease Neuroimaging Initiati - PLoS ONE (2015)

Longitudinal changes of cognitive function over 2 years across AD subtypes.Baseline, 1-year, and 2-year follow-up data on (A) MMSE indicating global cognition, (B) ADNI-Mem indicating memory function and (C) ADNI-EF indicating executive function are plotted, with means and standard errors. AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; MMSE; Mini-mental state examination; ADNI-Mem, composite score of memory function; ADNI-EF, composite score of executive function.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664412&req=5

pone.0142756.g002: Longitudinal changes of cognitive function over 2 years across AD subtypes.Baseline, 1-year, and 2-year follow-up data on (A) MMSE indicating global cognition, (B) ADNI-Mem indicating memory function and (C) ADNI-EF indicating executive function are plotted, with means and standard errors. AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; MMSE; Mini-mental state examination; ADNI-Mem, composite score of memory function; ADNI-EF, composite score of executive function.
Mentions: Upon LMM analyses of neuropsychological measures over 2 years in AD subjects, the subtype-by-time interaction, the subtype and time effects were all significant (S2 Table). Compared to the BI, the BS showed the slowest progression rates and the HA also showed relatively slow progression. In contrast, the CA showed the most rapid rates of cognitive decline over 2 years among the subtypes (Fig 2, S3 Table).

Bottom Line: Baseline and longitudinal changes of clinical characteristics over 2 years were compared across subtypes.These subtypes showed different progression rates over 2 years; and all subtypes had significantly lower CSF amyloid-β 1-42 levels compared to CN.CSF biomarker analysis suggests the presence of Aβ neuropathology irrespective of subtypes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

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-β 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 Aβ 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.

Show MeSH
Related in: MedlinePlus