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, María M. Corrada

Research output: Contribution to journalArticleAcademicpeer-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 languageEnglish
Pages (from-to)1827-1834
Number of pages8
JournalJournal of the American Geriatrics Society
Volume67
Issue number9
Early online date6 Jun 2019
DOIs
Publication statusPublished - 1 Sep 2019

Cite this

Legdeur, Nienke ; Visser, Pieter Jelle ; Woodworth, Davis C. ; Muller, Majon ; Fletcher, Evan ; Maillard, Pauline ; Scheltens, Philip ; DeCarli, Charles ; Kawas, Claudia H. ; Corrada, María M. / White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition : The 90+ Study. In: Journal of the American Geriatrics Society. 2019 ; Vol. 67, No. 9. pp. 1827-1834.
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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.",
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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, {Mar{\'i}a M.}",
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White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition : The 90+ Study. / Legdeur, Nienke; Visser, Pieter Jelle; Woodworth, Davis C.; Muller, Majon; Fletcher, Evan; Maillard, Pauline; Scheltens, Philip; DeCarli, Charles; Kawas, Claudia H.; Corrada, María M.

In: Journal of the American Geriatrics Society, Vol. 67, No. 9, 01.09.2019, p. 1827-1834.

Research output: Contribution to journalArticleAcademicpeer-review

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, María M.

N1 - © 2019 The American Geriatrics Society.

PY - 2019/9/1

Y1 - 2019/9/1

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 - cognitive functioning

KW - hippocampal atrophy

KW - oldest-old

KW - white matter hyperintensities

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