Metabolic reserve as a determinant of cognitive aging

Alexis M. Stranahan, Mark P. Mattson

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) represent points on a continuum of cognitive performance in aged populations. Cognition may be impaired or preserved in the context of brain aging. One theory to account for memory maintenance in the context of extensive pathology involves 'cognitive reserve', or the ability to compensate for neuropathology through greater recruitment of remaining neurons. In this review, we propose a complementary hypothesis of 'metabolic reserve', where a brain with high metabolic reserve is characterized by the presence of neuronal circuits that respond adaptively to perturbations in cellular and somatic energy metabolism and thereby protects against declining cognition. Lifestyle determinants of metabolic reserve, such as exercise, reduced caloric intake, and intake of specific dietary components can promote neuroprotection, while pathological states arising from sedentary lifestyles and excessive caloric intake contribute to neuronal endangerment. This bidirectional relationship between metabolism and cognition may be mediated by alterations in central insulin and neurotrophic factor signaling and glucose metabolism, with downstream consequences for accumulation of amyloid-β and hyperphosphorylated tau. The metabolic reserve hypothesis is supported by epidemiological findings and the spectrum of individual cognitive trajectories during aging, with additional data from animal models identifying potential mechanisms for this relationship. Identification of biomarkers for metabolic reserve could assist in generating a predictive model for the likelihood of cognitive decline with aging.

Original languageEnglish (US)
Pages (from-to)S5-S13
JournalJournal of Alzheimer's Disease
Volume30
Issue numberSUPPL.2
DOIs
StatePublished - 2012

Fingerprint

Cognitive Reserve
Cognition
Energy Intake
Sedentary Lifestyle
Aptitude
Nerve Growth Factors
Amyloid
Energy Metabolism
Life Style
Alzheimer Disease
Animal Models
Biomarkers
Maintenance
Insulin
Pathology
Neurons
Glucose
Brain
Population
Cognitive Aging

Keywords

  • Brain-derived neurotrophic factor (BDNF)
  • caloric restriction
  • diabetes
  • diet
  • exercise
  • insulin
  • metabolic syndrome
  • neurodegeneration

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Metabolic reserve as a determinant of cognitive aging. / Stranahan, Alexis M.; Mattson, Mark P.

In: Journal of Alzheimer's Disease, Vol. 30, No. SUPPL.2, 2012, p. S5-S13.

Research output: Contribution to journalReview article

Stranahan, Alexis M. ; Mattson, Mark P. / Metabolic reserve as a determinant of cognitive aging. In: Journal of Alzheimer's Disease. 2012 ; Vol. 30, No. SUPPL.2. pp. S5-S13.
@article{9854e3f185754231877a8d44151f1193,
title = "Metabolic reserve as a determinant of cognitive aging",
abstract = "Mild cognitive impairment (MCI) and Alzheimer's disease (AD) represent points on a continuum of cognitive performance in aged populations. Cognition may be impaired or preserved in the context of brain aging. One theory to account for memory maintenance in the context of extensive pathology involves 'cognitive reserve', or the ability to compensate for neuropathology through greater recruitment of remaining neurons. In this review, we propose a complementary hypothesis of 'metabolic reserve', where a brain with high metabolic reserve is characterized by the presence of neuronal circuits that respond adaptively to perturbations in cellular and somatic energy metabolism and thereby protects against declining cognition. Lifestyle determinants of metabolic reserve, such as exercise, reduced caloric intake, and intake of specific dietary components can promote neuroprotection, while pathological states arising from sedentary lifestyles and excessive caloric intake contribute to neuronal endangerment. This bidirectional relationship between metabolism and cognition may be mediated by alterations in central insulin and neurotrophic factor signaling and glucose metabolism, with downstream consequences for accumulation of amyloid-β and hyperphosphorylated tau. The metabolic reserve hypothesis is supported by epidemiological findings and the spectrum of individual cognitive trajectories during aging, with additional data from animal models identifying potential mechanisms for this relationship. Identification of biomarkers for metabolic reserve could assist in generating a predictive model for the likelihood of cognitive decline with aging.",
keywords = "Brain-derived neurotrophic factor (BDNF), caloric restriction, diabetes, diet, exercise, insulin, metabolic syndrome, neurodegeneration",
author = "Stranahan, {Alexis M.} and Mattson, {Mark P.}",
year = "2012",
doi = "10.3233/JAD-2011-110899",
language = "English (US)",
volume = "30",
pages = "S5--S13",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "SUPPL.2",

}

TY - JOUR

T1 - Metabolic reserve as a determinant of cognitive aging

AU - Stranahan, Alexis M.

AU - Mattson, Mark P.

PY - 2012

Y1 - 2012

N2 - Mild cognitive impairment (MCI) and Alzheimer's disease (AD) represent points on a continuum of cognitive performance in aged populations. Cognition may be impaired or preserved in the context of brain aging. One theory to account for memory maintenance in the context of extensive pathology involves 'cognitive reserve', or the ability to compensate for neuropathology through greater recruitment of remaining neurons. In this review, we propose a complementary hypothesis of 'metabolic reserve', where a brain with high metabolic reserve is characterized by the presence of neuronal circuits that respond adaptively to perturbations in cellular and somatic energy metabolism and thereby protects against declining cognition. Lifestyle determinants of metabolic reserve, such as exercise, reduced caloric intake, and intake of specific dietary components can promote neuroprotection, while pathological states arising from sedentary lifestyles and excessive caloric intake contribute to neuronal endangerment. This bidirectional relationship between metabolism and cognition may be mediated by alterations in central insulin and neurotrophic factor signaling and glucose metabolism, with downstream consequences for accumulation of amyloid-β and hyperphosphorylated tau. The metabolic reserve hypothesis is supported by epidemiological findings and the spectrum of individual cognitive trajectories during aging, with additional data from animal models identifying potential mechanisms for this relationship. Identification of biomarkers for metabolic reserve could assist in generating a predictive model for the likelihood of cognitive decline with aging.

AB - Mild cognitive impairment (MCI) and Alzheimer's disease (AD) represent points on a continuum of cognitive performance in aged populations. Cognition may be impaired or preserved in the context of brain aging. One theory to account for memory maintenance in the context of extensive pathology involves 'cognitive reserve', or the ability to compensate for neuropathology through greater recruitment of remaining neurons. In this review, we propose a complementary hypothesis of 'metabolic reserve', where a brain with high metabolic reserve is characterized by the presence of neuronal circuits that respond adaptively to perturbations in cellular and somatic energy metabolism and thereby protects against declining cognition. Lifestyle determinants of metabolic reserve, such as exercise, reduced caloric intake, and intake of specific dietary components can promote neuroprotection, while pathological states arising from sedentary lifestyles and excessive caloric intake contribute to neuronal endangerment. This bidirectional relationship between metabolism and cognition may be mediated by alterations in central insulin and neurotrophic factor signaling and glucose metabolism, with downstream consequences for accumulation of amyloid-β and hyperphosphorylated tau. The metabolic reserve hypothesis is supported by epidemiological findings and the spectrum of individual cognitive trajectories during aging, with additional data from animal models identifying potential mechanisms for this relationship. Identification of biomarkers for metabolic reserve could assist in generating a predictive model for the likelihood of cognitive decline with aging.

KW - Brain-derived neurotrophic factor (BDNF)

KW - caloric restriction

KW - diabetes

KW - diet

KW - exercise

KW - insulin

KW - metabolic syndrome

KW - neurodegeneration

UR - http://www.scopus.com/inward/record.url?scp=84862656430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862656430&partnerID=8YFLogxK

U2 - 10.3233/JAD-2011-110899

DO - 10.3233/JAD-2011-110899

M3 - Review article

C2 - 22045480

AN - SCOPUS:84862656430

VL - 30

SP - S5-S13

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - SUPPL.2

ER -