Abstract
Background: Understanding contributions of different brain pathologies to domain-specific cognitive trajectories in the oldest old is crucial to guide future intervention studies. Methods: Two-hundred-twenty Oregon Alzheimer's Disease Center research participants who were cognitively intact at entry were followed on average for 7.3 years with annual neuropsychological testing until death (mean age, 93.7 y) and autopsy. Mixed effects models examined the relationship between trajectories in memory, verbal fluency, and mini-mental state examination (MMSE) and pathology (neurofibrillary tangles, neuritic plaques, gross infarcts, hippocampal sclerosis, Lewy bodies, APOE genotype, age at death, and years of education). The association between the MMSE trajectory and pathologic variables were examined using a Poisson model with MMSE errors as outcomes given the nonlinear distribution of MMSE scores. Results: Memory trajectory was associated with the APOϵ4 allele (P=0.006). Verbal fluency trajectory was associated with gross infarcts (P=0.008). MMSE trajectory was associated with high Braak scores (P=0.03), gross infarcts (P<0.0001), hippocampal sclerosis (P=0.003), moderate neuritic plaques (P=0.04), and the APOϵ4 allele (P=0.02). Conclusions: The association between trajectory of decline in global cognitive scores and multiple brain pathologies highlights the importance of accounting for comorbid pathologies in therapeutic trials aimed at one specific pathology in the oldest old. Only the APOϵ4 allele showed an association with memory decline, despite accounting for Alzheimer's disease pathology, suggesting that APOE may be involved in mechanisms beyond amyloid metabolism in its role in memory. Further studies are needed to examine the role of APOE in brain aging.
| Original language | English (US) |
|---|---|
| Journal | Alzheimer Disease and Associated Disorders |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- cognition
- neuropathology
- oldest old
ASJC Scopus subject areas
- Clinical Psychology
- Gerontology
- Geriatrics and Gerontology
- Psychiatry and Mental health
Cite this
Pathologies Underlying Longitudinal Cognitive Decline in the Oldest Old. / Nguyen, Madeline T.; Mattek, Nora; Woltjer, Randall (Randy); Howieson, Diane; Silbert, Lisa; Hofer, Scott; Kaye, Jeffrey; Dodge, Hiroko; Erten-Lyons, Deniz.
In: Alzheimer Disease and Associated Disorders, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pathologies Underlying Longitudinal Cognitive Decline in the Oldest Old
AU - Nguyen, Madeline T.
AU - Mattek, Nora
AU - Woltjer, Randall (Randy)
AU - Howieson, Diane
AU - Silbert, Lisa
AU - Hofer, Scott
AU - Kaye, Jeffrey
AU - Dodge, Hiroko
AU - Erten-Lyons, Deniz
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Understanding contributions of different brain pathologies to domain-specific cognitive trajectories in the oldest old is crucial to guide future intervention studies. Methods: Two-hundred-twenty Oregon Alzheimer's Disease Center research participants who were cognitively intact at entry were followed on average for 7.3 years with annual neuropsychological testing until death (mean age, 93.7 y) and autopsy. Mixed effects models examined the relationship between trajectories in memory, verbal fluency, and mini-mental state examination (MMSE) and pathology (neurofibrillary tangles, neuritic plaques, gross infarcts, hippocampal sclerosis, Lewy bodies, APOE genotype, age at death, and years of education). The association between the MMSE trajectory and pathologic variables were examined using a Poisson model with MMSE errors as outcomes given the nonlinear distribution of MMSE scores. Results: Memory trajectory was associated with the APOϵ4 allele (P=0.006). Verbal fluency trajectory was associated with gross infarcts (P=0.008). MMSE trajectory was associated with high Braak scores (P=0.03), gross infarcts (P<0.0001), hippocampal sclerosis (P=0.003), moderate neuritic plaques (P=0.04), and the APOϵ4 allele (P=0.02). Conclusions: The association between trajectory of decline in global cognitive scores and multiple brain pathologies highlights the importance of accounting for comorbid pathologies in therapeutic trials aimed at one specific pathology in the oldest old. Only the APOϵ4 allele showed an association with memory decline, despite accounting for Alzheimer's disease pathology, suggesting that APOE may be involved in mechanisms beyond amyloid metabolism in its role in memory. Further studies are needed to examine the role of APOE in brain aging.
AB - Background: Understanding contributions of different brain pathologies to domain-specific cognitive trajectories in the oldest old is crucial to guide future intervention studies. Methods: Two-hundred-twenty Oregon Alzheimer's Disease Center research participants who were cognitively intact at entry were followed on average for 7.3 years with annual neuropsychological testing until death (mean age, 93.7 y) and autopsy. Mixed effects models examined the relationship between trajectories in memory, verbal fluency, and mini-mental state examination (MMSE) and pathology (neurofibrillary tangles, neuritic plaques, gross infarcts, hippocampal sclerosis, Lewy bodies, APOE genotype, age at death, and years of education). The association between the MMSE trajectory and pathologic variables were examined using a Poisson model with MMSE errors as outcomes given the nonlinear distribution of MMSE scores. Results: Memory trajectory was associated with the APOϵ4 allele (P=0.006). Verbal fluency trajectory was associated with gross infarcts (P=0.008). MMSE trajectory was associated with high Braak scores (P=0.03), gross infarcts (P<0.0001), hippocampal sclerosis (P=0.003), moderate neuritic plaques (P=0.04), and the APOϵ4 allele (P=0.02). Conclusions: The association between trajectory of decline in global cognitive scores and multiple brain pathologies highlights the importance of accounting for comorbid pathologies in therapeutic trials aimed at one specific pathology in the oldest old. Only the APOϵ4 allele showed an association with memory decline, despite accounting for Alzheimer's disease pathology, suggesting that APOE may be involved in mechanisms beyond amyloid metabolism in its role in memory. Further studies are needed to examine the role of APOE in brain aging.
KW - cognition
KW - neuropathology
KW - oldest old
UR - http://www.scopus.com/inward/record.url?scp=85052671143&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052671143&partnerID=8YFLogxK
U2 - 10.1097/WAD.0000000000000265
DO - 10.1097/WAD.0000000000000265
M3 - Article
C2 - 30052535
AN - SCOPUS:85052671143
JO - Alzheimer Disease and Associated Disorders
JF - Alzheimer Disease and Associated Disorders
SN - 0893-0341
ER -