Two distinct classes of degenerative change are independently linked to clinical progression in mild cognitive impairment

Jean-Philippe Coutu; Emily R Lindemer; Ender Konukoglu; David H Salat; Alzheimer's Disease Neuroimaging Initiative (ADNI)

doi:10.1016/j.neurobiolaging.2017.02.005

Two distinct classes of degenerative change are independently linked to clinical progression in mild cognitive impairment

Neurobiol Aging. 2017 Jun:54:1-9. doi: 10.1016/j.neurobiolaging.2017.02.005. Epub 2017 Feb 16.

Authors

Jean-Philippe Coutu¹, Emily R Lindemer², Ender Konukoglu³, David H Salat⁴; Alzheimer's Disease Neuroimaging Initiative (ADNI)

Affiliations

¹ MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Departments of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
² MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Departments of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³ MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Departments of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴ MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Departments of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA.

PMID: 28286328
PMCID: PMC5519085
DOI: 10.1016/j.neurobiolaging.2017.02.005

Abstract

We previously demonstrated 2 statistically distinct factors of degeneration in Alzheimer's disease: one strongly related to white matter damage and age interpreted as "age- and vascular-related", and the other related to cortical atrophy thought to represent "neurodegenerative changes associated with Alzheimer's disease". Those factors are now replicated in a distinct cross-sectional data set of 364 participants from the Alzheimer's Disease Neuroimaging Initiative and their interpretation is improved using correlations with CSF biomarkers. Furthermore, we now show that changes in both factors over 2 years are independently associated with decline in Mini-Mental State Examination score in a longitudinal subset of 116 individuals with mild cognitive impairment. Progression in the "age- and vascular-related" factor was greater for individuals with 2 APOE ε4 alleles and linked to a greater attributable change in Mini-Mental State Examination than the "neurodegenerative" factor. These results suggest benefits of targeting white matter and vascular health to complement interventions focused on the neurodegenerative aspect of the disease, even in individuals with little discernable vascular comorbidity.

Keywords: Alzheimer's disease; CSF biomarkers; Cognitive decline; Longitudinal cohort study; Mild cognitive impairment; Small-vessel disease; White matter.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cerebral Cortex / diagnostic imaging
Cerebral Cortex / pathology*
Cognitive Dysfunction / diagnostic imaging*
Cognitive Dysfunction / pathology*
Cross-Sectional Studies
Datasets as Topic
Disease Progression
Female
Humans
Male
Nerve Degeneration*
Neuroimaging
White Matter / diagnostic imaging
White Matter / pathology*

Abstract

Publication types

MeSH terms

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