Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume

Owen Carmichael, Jing Xie, Evan Fletcher, Baljeet Singh, Charles DeCarli

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed localized components analysis (LoCA) was used to identify 7 independent patterns of HP atrophy among 390 semiautomatically delineated HP from baseline magnetic resonance imaging of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among cognitively normal participants, multiple measures of localized HP atrophy were significantly associated with CSF amyloid concentration, while total HP volume was not. In addition, among all participants, localized HP atrophy measures and total HP volume were both independently and additively associated with CSF tau concentration, performance on numerous neuropsychological tests, and discrimination between normal, mild cognitive impairment (MCI), and AD clinical diagnostic groups. Together, these results suggest that regional measures of hippocampal atrophy provided by localized components analysis may be more sensitive than total HP volume to the effects of AD pathology burden among cognitively normal individuals and may provide information about HP regions whose deficits may have especially profound cognitive consequences throughout the AD clinical course.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume33
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Cognition
Hippocampus
Pathology
Alzheimer Disease
Atrophy
Cerebrospinal Fluid
Amyloid
Magnetic Resonance Imaging
Neuropsychological Tests
Statistical Models
Pathologic Processes
Neuroimaging

Keywords

  • Alzheimer's disease
  • Biomarkers
  • Hippocampus
  • Morphometry
  • Shape analysis

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume. / Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; DeCarli, Charles.

In: Neurobiology of Aging, Vol. 33, No. 6, 06.2012.

Research output: Contribution to journalArticle

@article{4745e1de7bfe4b96be9ad1a15bfd5c98,
title = "Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume",
abstract = "Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed localized components analysis (LoCA) was used to identify 7 independent patterns of HP atrophy among 390 semiautomatically delineated HP from baseline magnetic resonance imaging of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among cognitively normal participants, multiple measures of localized HP atrophy were significantly associated with CSF amyloid concentration, while total HP volume was not. In addition, among all participants, localized HP atrophy measures and total HP volume were both independently and additively associated with CSF tau concentration, performance on numerous neuropsychological tests, and discrimination between normal, mild cognitive impairment (MCI), and AD clinical diagnostic groups. Together, these results suggest that regional measures of hippocampal atrophy provided by localized components analysis may be more sensitive than total HP volume to the effects of AD pathology burden among cognitively normal individuals and may provide information about HP regions whose deficits may have especially profound cognitive consequences throughout the AD clinical course.",
keywords = "Alzheimer's disease, Biomarkers, Hippocampus, Morphometry, Shape analysis",
author = "Owen Carmichael and Jing Xie and Evan Fletcher and Baljeet Singh and Charles DeCarli",
year = "2012",
month = "6",
doi = "10.1016/j.neurobiolaging.2011.08.016",
language = "English (US)",
volume = "33",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume

AU - Carmichael, Owen

AU - Xie, Jing

AU - Fletcher, Evan

AU - Singh, Baljeet

AU - DeCarli, Charles

PY - 2012/6

Y1 - 2012/6

N2 - Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed localized components analysis (LoCA) was used to identify 7 independent patterns of HP atrophy among 390 semiautomatically delineated HP from baseline magnetic resonance imaging of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among cognitively normal participants, multiple measures of localized HP atrophy were significantly associated with CSF amyloid concentration, while total HP volume was not. In addition, among all participants, localized HP atrophy measures and total HP volume were both independently and additively associated with CSF tau concentration, performance on numerous neuropsychological tests, and discrimination between normal, mild cognitive impairment (MCI), and AD clinical diagnostic groups. Together, these results suggest that regional measures of hippocampal atrophy provided by localized components analysis may be more sensitive than total HP volume to the effects of AD pathology burden among cognitively normal individuals and may provide information about HP regions whose deficits may have especially profound cognitive consequences throughout the AD clinical course.

AB - Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed localized components analysis (LoCA) was used to identify 7 independent patterns of HP atrophy among 390 semiautomatically delineated HP from baseline magnetic resonance imaging of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among cognitively normal participants, multiple measures of localized HP atrophy were significantly associated with CSF amyloid concentration, while total HP volume was not. In addition, among all participants, localized HP atrophy measures and total HP volume were both independently and additively associated with CSF tau concentration, performance on numerous neuropsychological tests, and discrimination between normal, mild cognitive impairment (MCI), and AD clinical diagnostic groups. Together, these results suggest that regional measures of hippocampal atrophy provided by localized components analysis may be more sensitive than total HP volume to the effects of AD pathology burden among cognitively normal individuals and may provide information about HP regions whose deficits may have especially profound cognitive consequences throughout the AD clinical course.

KW - Alzheimer's disease

KW - Biomarkers

KW - Hippocampus

KW - Morphometry

KW - Shape analysis

UR - http://www.scopus.com/inward/record.url?scp=84859496272&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859496272&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2011.08.016

DO - 10.1016/j.neurobiolaging.2011.08.016

M3 - Article

C2 - 22169204

AN - SCOPUS:84859496272

VL - 33

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 6

ER -