White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition: The 90+Study

Nienke Legdeur; Pieter Jelle Visser; Davis C. Woodworth; Majon Muller; Evan Fletcher; Pauline Maillard; Philip Scheltens; Charles DeCarli; Claudia H. Kawas; Maria M. Corrada

doi:10.1111/jgs.15990

White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition: The 90+Study

Nienke Legdeur^*, Pieter Jelle Visser, Davis C. Woodworth, Majon Muller, Evan Fletcher, Pauline Maillard, Philip Scheltens, Charles DeCarli, Claudia H. Kawas, Maria M. Corrada

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVES To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old. DESIGN Ongoing longitudinal study. SETTING In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017. PARTICIPANTS Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment). MEASUREMENTS Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education. RESULTS Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline. CONCLUSION We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019

Original language	English
Pages (from-to)	1827-1834
Number of pages	8
Journal	Journal of the American Geriatrics Society
Volume	67
Issue number	9
DOIs	https://doi.org/10.1111/jgs.15990
Publication status	Published - Sept 2019

Keywords

white matter hyperintensities
hippocampal atrophy
cognitive functioning
oldest-old
SMALL-VESSEL DISEASE
MINI-MENTAL STATE
OLDEST-OLD
DEMENTIA
VOLUME
MRI
PATHOLOGIES
PREVALENCE
LESIONS

Access to Document

10.1111/jgs.15990

Cite this

@article{89f0f4906f844a959ca2893547f50aa0,

title = "White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition: The 90+Study",

abstract = "OBJECTIVES To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old. DESIGN Ongoing longitudinal study. SETTING In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017. PARTICIPANTS Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment). MEASUREMENTS Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education. RESULTS Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline. CONCLUSION We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019",

keywords = "white matter hyperintensities, hippocampal atrophy, cognitive functioning, oldest-old, SMALL-VESSEL DISEASE, MINI-MENTAL STATE, OLDEST-OLD, DEMENTIA, VOLUME, MRI, PATHOLOGIES, PREVALENCE, LESIONS",

author = "Nienke Legdeur and Visser, {Pieter Jelle} and Woodworth, {Davis C.} and Majon Muller and Evan Fletcher and Pauline Maillard and Philip Scheltens and Charles DeCarli and Kawas, {Claudia H.} and Corrada, {Maria M.}",

note = "Funding Information: We thank the participants, their relatives, and the staff of The 90+ Study. Financial Disclosure: This work was supported by grants from the National Institutes of Health (R01AG021055 and P30AG10129), the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement no. 115372, and Alzheimer Nederland. Conflict of Interest: The authors do not have any conflicts of interest. Author Contributions: All authors made substantial contributions to the manuscript. Mar{\'i}a M. Corrada, Claudia H. Kawas, Philip Scheltens, and Nienke Legdeur created the design and concept of the study. Nienke Legdeur performed the data analyses, and Mar{\'i}a M. Corrada assisted with the data analyses. Evan Fletcher, Pauline Maillard, and Charles DeCarli performed the MRI analyses. Nienke Legdeur drafted the first and final versions of the manuscript. All authors contributed to and approved the final version. Sponsor's Role: The funding organizations had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2019 The American Geriatrics Society",

year = "2019",

month = sep,

doi = "10.1111/jgs.15990",

language = "English",

volume = "67",

pages = "1827--1834",

journal = "Journal of the American Geriatrics Society",

issn = "0002-8614",

publisher = "Wiley",

number = "9",

}

TY - JOUR

T1 - White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition

T2 - The 90+Study

AU - Legdeur, Nienke

AU - Visser, Pieter Jelle

AU - Woodworth, Davis C.

AU - Muller, Majon

AU - Fletcher, Evan

AU - Maillard, Pauline

AU - Scheltens, Philip

AU - DeCarli, Charles

AU - Kawas, Claudia H.

AU - Corrada, Maria M.

N1 - Funding Information: We thank the participants, their relatives, and the staff of The 90+ Study. Financial Disclosure: This work was supported by grants from the National Institutes of Health (R01AG021055 and P30AG10129), the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement no. 115372, and Alzheimer Nederland. Conflict of Interest: The authors do not have any conflicts of interest. Author Contributions: All authors made substantial contributions to the manuscript. María M. Corrada, Claudia H. Kawas, Philip Scheltens, and Nienke Legdeur created the design and concept of the study. Nienke Legdeur performed the data analyses, and María M. Corrada assisted with the data analyses. Evan Fletcher, Pauline Maillard, and Charles DeCarli performed the MRI analyses. Nienke Legdeur drafted the first and final versions of the manuscript. All authors contributed to and approved the final version. Sponsor's Role: The funding organizations had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Publisher Copyright: © 2019 The American Geriatrics Society

PY - 2019/9

Y1 - 2019/9

N2 - OBJECTIVES To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old. DESIGN Ongoing longitudinal study. SETTING In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017. PARTICIPANTS Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment). MEASUREMENTS Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education. RESULTS Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline. CONCLUSION We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019

AB - OBJECTIVES To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old. DESIGN Ongoing longitudinal study. SETTING In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017. PARTICIPANTS Individuals from The 90+ Study with a valid brain MRI scan (N = 141; 94 cognitively normal and 47 with cognitive impairment). MEASUREMENTS Cognitive testing was performed every 6 months with a mean follow-up of 2 years and included these tests: Mini-Mental State Examination (MMSE), modified MMSE (3MS), California Verbal Learning Test (CVLT) immediate recall over four trials and delayed recall, Digit Span Backward, Animal Fluency, and Trail Making Test (TMT) A, B, and C. We used one linear mixed model for each cognitive test to study the baseline and longitudinal association of WMH and hippocampal volume (HV) with cognition. Models were adjusted for age, sex, and education. RESULTS Mean age was 94.3 years (standard deviation [SD] = 3.2 y). At baseline, higher WMH volumes were associated with worse scores on the 3MS, CVLT immediate and delayed recall, and TMT B. Lower HVs were associated with worse baseline scores on all cognitive tests, except for the Digit Span Backward. Longitudinally, higher WMH and lower HVs were associated with faster decline in the 3MS and MMSE, and lower HV was also associated with faster decline in the CVLT immediate recall. No association was observed between WMH and HV and no interaction between WMH and HV in their association with baseline cognition or cognitive decline. CONCLUSION We show that WMH and hippocampal atrophy have an independent, negative effect on cognition that make these biomarkers relevant to evaluate in the diagnostic work-up of the oldest-old individuals with cognitive complaints. However, the predictive value of WMH for cognitive decline seems to be less evident in the oldest-old compared with a younger group of older adults. J Am Geriatr Soc 67:1827-1834, 2019

KW - white matter hyperintensities

KW - hippocampal atrophy

KW - cognitive functioning

KW - oldest-old

KW - SMALL-VESSEL DISEASE

KW - MINI-MENTAL STATE

KW - OLDEST-OLD

KW - DEMENTIA

KW - VOLUME

KW - MRI

KW - PATHOLOGIES

KW - PREVALENCE

KW - LESIONS

U2 - 10.1111/jgs.15990

DO - 10.1111/jgs.15990

M3 - Article

C2 - 31169919

SN - 0002-8614

VL - 67

SP - 1827

EP - 1834

JO - Journal of the American Geriatrics Society

JF - Journal of the American Geriatrics Society

IS - 9

ER -