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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

CSF biomarker levels.The dot plots of CSF biomarkers in CN and AD subtypes. Bars indicates median and IQR. (A) CSF Aβ1–42, (B) CSF t-tau, (C) CSF p-tau, (D) t-tau/Aβ1–42 ratio, (E) p-tau/Aβ1–42 ratio. CN, Cognitively normal; AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; CSF, Cerebrospinal fluid; Aβ1–42 = Amyloid-β 1–42 peptide; t-tau, total tau; p-tau, phosphorylated tau.
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pone.0142756.g003: CSF biomarker levels.The dot plots of CSF biomarkers in CN and AD subtypes. Bars indicates median and IQR. (A) CSF Aβ1–42, (B) CSF t-tau, (C) CSF p-tau, (D) t-tau/Aβ1–42 ratio, (E) p-tau/Aβ1–42 ratio. CN, Cognitively normal; AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; CSF, Cerebrospinal fluid; Aβ1–42 = Amyloid-β 1–42 peptide; t-tau, total tau; p-tau, phosphorylated tau.

Mentions: Of subjects for whom CSF data were available, all AD subtypes had significantly lower CSF Aβ1–42 levels compared to CN (Fig 3, Table 4). In terms of CSF tau level, the BI, HA and CA, but not BS, showed significant increase in t-tau, p-tau level, t-tau/Aβ1–42 and p-tau/Aβ1–42 ratio compared to CN. However, no significant group differences were found in all CSF biomarkers across the AD subtypes. In addition, all of the four AD subtypes were identified among the subgroup of CSF Aβ-positive AD subjects (n = 80), with relatively similar frequency (58%, 21%, 15%, and 6% for the BI, HA, CA and BS, respectively).


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)

CSF biomarker levels.The dot plots of CSF biomarkers in CN and AD subtypes. Bars indicates median and IQR. (A) CSF Aβ1–42, (B) CSF t-tau, (C) CSF p-tau, (D) t-tau/Aβ1–42 ratio, (E) p-tau/Aβ1–42 ratio. CN, Cognitively normal; AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; CSF, Cerebrospinal fluid; Aβ1–42 = Amyloid-β 1–42 peptide; t-tau, total tau; p-tau, phosphorylated tau.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0142756.g003: CSF biomarker levels.The dot plots of CSF biomarkers in CN and AD subtypes. Bars indicates median and IQR. (A) CSF Aβ1–42, (B) CSF t-tau, (C) CSF p-tau, (D) t-tau/Aβ1–42 ratio, (E) p-tau/Aβ1–42 ratio. CN, Cognitively normal; AD, Alzheimer’s disease; BI, Both impaired; HA, Hippocampal atrophy only; CA, Cortical atrophy only; BS, Both spared; CSF, Cerebrospinal fluid; Aβ1–42 = Amyloid-β 1–42 peptide; t-tau, total tau; p-tau, phosphorylated tau.
Mentions: Of subjects for whom CSF data were available, all AD subtypes had significantly lower CSF Aβ1–42 levels compared to CN (Fig 3, Table 4). In terms of CSF tau level, the BI, HA and CA, but not BS, showed significant increase in t-tau, p-tau level, t-tau/Aβ1–42 and p-tau/Aβ1–42 ratio compared to CN. However, no significant group differences were found in all CSF biomarkers across the AD subtypes. In addition, all of the four AD subtypes were identified among the subgroup of CSF Aβ-positive AD subjects (n = 80), with relatively similar frequency (58%, 21%, 15%, and 6% for the BI, HA, CA and BS, respectively).

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