Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging

Prashanthi Vemuri; Timothy G. Lesnick; David S. Knopman; Scott A. Przybelski; Robert I. Reid; Michelle M. Mielke; Jonathan Graff-Radford; Val J. Lowe; Mary M. Machulda; Ronald C. Petersen; Clifford R. Jack

doi:10.1002/ana.25600

Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging

Prashanthi Vemuri, Timothy G. Lesnick, David S. Knopman, Scott A. Przybelski, Robert I. Reid, Michelle M. Mielke, Jonathan Graff-Radford, Val J. Lowe, Mary M. Machulda, Ronald C. Petersen, Clifford R. Jack

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

8 Scopus citations

Abstract

Objective: To investigate the multifactorial processes underlying cognitive aging based on the hypothesis that multiple causal pathways and mechanisms (amyloid, vascular, and resilience) influence longitudinal cognitive decline in each individual through worsening brain health. Methods: We identified 1,230 elderly subjects (aged ≥50 years) with an average of 4.9 years of clinical follow-up and with amyloid positron emission tomography, diffusion tensor imaging, and structural magnetic resonance imaging scans from the population-based Mayo Clinic Study of Aging. We examined imaging markers of amyloid and brain health (white matter microstructural integrity and cortical thinning), systemic vascular health preceding the imaging markers, and early to midlife intellectual enrichment to predict longitudinal cognitive trajectories. We used latent growth curve models for modeling longitudinal cognitive decline. Results: All the pathways (amyloid, vascular, resilience) converged through their effects on cortical thinning and worsening cognition and together explained patterns in cognitive decline. Resilience and vascular pathways (aging process, sex differences, education/occupation, and systemic vascular health) had significant impact on white matter microstructural integrity. Education/occupation levels contributed to white matter integrity through systemic vascular health. Worsening white matter integrity contributed to significant cortical thinning and subsequently longitudinal cognitive decline. Baseline amyloidosis contributed to a significant proportion of cognitive decline that accelerated with longer follow-up times, and its primary impact was through cortical thinning. Interpretation: We developed an integrated framework to help explain the dynamic and complex process of cognitive aging by considering key causal pathways. Such an approach is important for both better comprehension of cognitive aging processes and will aid in the development of successful intervention strategies. ANN NEUROL 2019;86:866–877.

Original language	English (US)
Pages (from-to)	866-877
Number of pages	12
Journal	Annals of neurology
Volume	86
Issue number	6
DOIs	https://doi.org/10.1002/ana.25600
State	Published - Dec 1 2019

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/ana.25600

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@article{f7d07eb1b3054cebb1a71af7fd755bb5,

title = "Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging",

abstract = "Objective: To investigate the multifactorial processes underlying cognitive aging based on the hypothesis that multiple causal pathways and mechanisms (amyloid, vascular, and resilience) influence longitudinal cognitive decline in each individual through worsening brain health. Methods: We identified 1,230 elderly subjects (aged ≥50 years) with an average of 4.9 years of clinical follow-up and with amyloid positron emission tomography, diffusion tensor imaging, and structural magnetic resonance imaging scans from the population-based Mayo Clinic Study of Aging. We examined imaging markers of amyloid and brain health (white matter microstructural integrity and cortical thinning), systemic vascular health preceding the imaging markers, and early to midlife intellectual enrichment to predict longitudinal cognitive trajectories. We used latent growth curve models for modeling longitudinal cognitive decline. Results: All the pathways (amyloid, vascular, resilience) converged through their effects on cortical thinning and worsening cognition and together explained patterns in cognitive decline. Resilience and vascular pathways (aging process, sex differences, education/occupation, and systemic vascular health) had significant impact on white matter microstructural integrity. Education/occupation levels contributed to white matter integrity through systemic vascular health. Worsening white matter integrity contributed to significant cortical thinning and subsequently longitudinal cognitive decline. Baseline amyloidosis contributed to a significant proportion of cognitive decline that accelerated with longer follow-up times, and its primary impact was through cortical thinning. Interpretation: We developed an integrated framework to help explain the dynamic and complex process of cognitive aging by considering key causal pathways. Such an approach is important for both better comprehension of cognitive aging processes and will aid in the development of successful intervention strategies. ANN NEUROL 2019;86:866–877.",

author = "Prashanthi Vemuri and Lesnick, {Timothy G.} and Knopman, {David S.} and Przybelski, {Scott A.} and Reid, {Robert I.} and Mielke, {Michelle M.} and Jonathan Graff-Radford and Lowe, {Val J.} and Machulda, {Mary M.} and Petersen, {Ronald C.} and Jack, {Clifford R.}",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.",

year = "2019",

month = dec,

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doi = "10.1002/ana.25600",

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T1 - Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging

AU - Vemuri, Prashanthi

AU - Lesnick, Timothy G.

AU - Knopman, David S.

AU - Przybelski, Scott A.

AU - Reid, Robert I.

AU - Mielke, Michelle M.

AU - Graff-Radford, Jonathan

AU - Lowe, Val J.

AU - Machulda, Mary M.

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Objective: To investigate the multifactorial processes underlying cognitive aging based on the hypothesis that multiple causal pathways and mechanisms (amyloid, vascular, and resilience) influence longitudinal cognitive decline in each individual through worsening brain health. Methods: We identified 1,230 elderly subjects (aged ≥50 years) with an average of 4.9 years of clinical follow-up and with amyloid positron emission tomography, diffusion tensor imaging, and structural magnetic resonance imaging scans from the population-based Mayo Clinic Study of Aging. We examined imaging markers of amyloid and brain health (white matter microstructural integrity and cortical thinning), systemic vascular health preceding the imaging markers, and early to midlife intellectual enrichment to predict longitudinal cognitive trajectories. We used latent growth curve models for modeling longitudinal cognitive decline. Results: All the pathways (amyloid, vascular, resilience) converged through their effects on cortical thinning and worsening cognition and together explained patterns in cognitive decline. Resilience and vascular pathways (aging process, sex differences, education/occupation, and systemic vascular health) had significant impact on white matter microstructural integrity. Education/occupation levels contributed to white matter integrity through systemic vascular health. Worsening white matter integrity contributed to significant cortical thinning and subsequently longitudinal cognitive decline. Baseline amyloidosis contributed to a significant proportion of cognitive decline that accelerated with longer follow-up times, and its primary impact was through cortical thinning. Interpretation: We developed an integrated framework to help explain the dynamic and complex process of cognitive aging by considering key causal pathways. Such an approach is important for both better comprehension of cognitive aging processes and will aid in the development of successful intervention strategies. ANN NEUROL 2019;86:866–877.

AB - Objective: To investigate the multifactorial processes underlying cognitive aging based on the hypothesis that multiple causal pathways and mechanisms (amyloid, vascular, and resilience) influence longitudinal cognitive decline in each individual through worsening brain health. Methods: We identified 1,230 elderly subjects (aged ≥50 years) with an average of 4.9 years of clinical follow-up and with amyloid positron emission tomography, diffusion tensor imaging, and structural magnetic resonance imaging scans from the population-based Mayo Clinic Study of Aging. We examined imaging markers of amyloid and brain health (white matter microstructural integrity and cortical thinning), systemic vascular health preceding the imaging markers, and early to midlife intellectual enrichment to predict longitudinal cognitive trajectories. We used latent growth curve models for modeling longitudinal cognitive decline. Results: All the pathways (amyloid, vascular, resilience) converged through their effects on cortical thinning and worsening cognition and together explained patterns in cognitive decline. Resilience and vascular pathways (aging process, sex differences, education/occupation, and systemic vascular health) had significant impact on white matter microstructural integrity. Education/occupation levels contributed to white matter integrity through systemic vascular health. Worsening white matter integrity contributed to significant cortical thinning and subsequently longitudinal cognitive decline. Baseline amyloidosis contributed to a significant proportion of cognitive decline that accelerated with longer follow-up times, and its primary impact was through cortical thinning. Interpretation: We developed an integrated framework to help explain the dynamic and complex process of cognitive aging by considering key causal pathways. Such an approach is important for both better comprehension of cognitive aging processes and will aid in the development of successful intervention strategies. ANN NEUROL 2019;86:866–877.

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JO - Annals of neurology

JF - Annals of neurology

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ER -

Amyloid, Vascular, and Resilience Pathways Associated with Cognitive Aging

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