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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

Overall regional brain atrophy pattern of AD subtypes in voxel-based morphometry.Voxel-wise whole-brain comparison of regional GM volume after correction for multiple comparisons using family-wise error correction at p < 0.05 (k = 100). (A) to (D) show the regional patterns of GM volume loss in each AD subtype compared with CN. (A) CN vs. BI, (B) CN vs. HA, (C) CN vs. CA and (D) CN vs. BS. GM, Gray matter; AD, Alzheimer’s disease; CN, Cognitively normal; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared.
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pone.0142756.g001: Overall regional brain atrophy pattern of AD subtypes in voxel-based morphometry.Voxel-wise whole-brain comparison of regional GM volume after correction for multiple comparisons using family-wise error correction at p < 0.05 (k = 100). (A) to (D) show the regional patterns of GM volume loss in each AD subtype compared with CN. (A) CN vs. BI, (B) CN vs. HA, (C) CN vs. CA and (D) CN vs. BS. GM, Gray matter; AD, Alzheimer’s disease; CN, Cognitively normal; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared.

Mentions: To explore the overall regional GM atrophy pattern for each AD subtype, we conducted voxel-based analyses of the whole brain. As expected, the BI exhibited the most diffuse brain atrophy of all subtypes compared to CN, involving not only the bilateral temporal lobes but also the lateral fronto-parietal regions. The HA exhibited prominent atrophy only in the bilateral medial and inferior temporal regions including hippocampus. In contrast, the CA exhibited atrophy mainly on the lateral sides of the fronto-parieto-temporal cortices; both hippocampi were spared. The BS did not significantly differ in terms of GM volume compared to CN (Fig 1).


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)

Overall regional brain atrophy pattern of AD subtypes in voxel-based morphometry.Voxel-wise whole-brain comparison of regional GM volume after correction for multiple comparisons using family-wise error correction at p < 0.05 (k = 100). (A) to (D) show the regional patterns of GM volume loss in each AD subtype compared with CN. (A) CN vs. BI, (B) CN vs. HA, (C) CN vs. CA and (D) CN vs. BS. GM, Gray matter; AD, Alzheimer’s disease; CN, Cognitively normal; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0142756.g001: Overall regional brain atrophy pattern of AD subtypes in voxel-based morphometry.Voxel-wise whole-brain comparison of regional GM volume after correction for multiple comparisons using family-wise error correction at p < 0.05 (k = 100). (A) to (D) show the regional patterns of GM volume loss in each AD subtype compared with CN. (A) CN vs. BI, (B) CN vs. HA, (C) CN vs. CA and (D) CN vs. BS. GM, Gray matter; AD, Alzheimer’s disease; CN, Cognitively normal; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared.
Mentions: To explore the overall regional GM atrophy pattern for each AD subtype, we conducted voxel-based analyses of the whole brain. As expected, the BI exhibited the most diffuse brain atrophy of all subtypes compared to CN, involving not only the bilateral temporal lobes but also the lateral fronto-parietal regions. The HA exhibited prominent atrophy only in the bilateral medial and inferior temporal regions including hippocampus. In contrast, the CA exhibited atrophy mainly on the lateral sides of the fronto-parieto-temporal cortices; both hippocampi were spared. The BS did not significantly differ in terms of GM volume compared to CN (Fig 1).

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