The objective of this study was to investigate the relationship between accelerometer-measured physical activity (PA) and glucose metabolism in asymptomatic late-middle-aged adults. Ninety-three cognitively healthy late-middle-aged adults from the Wisconsin Registry for Alzheimer’s Prevention participated in this cross-sectional study. They underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and wore an accelerometer (ActiGraph GT3X+) to measure free-living PA. Accelerometer data yielded measures of light (LPA), moderate (MPA), and vigorous (VPA) intensity PA. FDG-PET images were scaled to the cerebellum and pons, and cerebral glucose metabolic rate was extracted from specific regions of interest (ROIs) known to be hypometabolic in AD, i.e., hippocampus, posterior cingulate, inferior temporal cortex, and angular gyrus. Regression analyses were utilized to examine the association between PA and glucose metabolism, while adjusting for potential confounds. There were associations between MPA and glucose metabolism in all ROIs examined. In contrast, LPA was not associated with glucose uptake in any ROI and VPA was only associated with hippocampal FDG uptake. Secondary analyses did not reveal associations between sedentary time and glucose metabolism in any of the ROIs. Exploratory voxel-wise analysis identified additional regions where MPA was significantly associated with glucose metabolism including the precuneus, supramarginal gyrus, amygdala, and middle frontal gyrus. These findings suggest that the intensity of PA is an important contributor to neuronal function in a late-middle-aged cohort, with MPA being the most salient. Prospective studies are necessary for fully elucidating the link between midlife engagement in PA and later life development of AD.
AlexanderGE, ChenK, PietriniP, RapoportSI, ReimanEM (2002) Longitudinal PET evaluation of cerebral metabolic decline in dementia: A potential outcome measure in Alzheimer’s disease treatment studies. Am J Psychiatry159, 738–745.
2.
de LeonMJ, FerrisSH, GeorgeAE, ReisbergB, ChristmanDR, KricheffII, WolfAP (1983) Computed tomography and positron emission transaxial tomography evaluations of normal aging and Alzheimer’s disease. J Cereb Blood Flow Metab3, 391–394.
3.
MosconiL, TsuiWH, De SantiS, LiJ, RusinekH, ConvitA, LiY, BoppanaM, de LeonMJ (2005) Reduced hippocampal metabolism in MCI and AD: Automated FDG-PET image analysis. Neurology64, 1860–1867.
4.
ReimanEM, CaselliRJ, YunLS, ChenK, BandyD, MinoshimaS, ThibodeauSN, OsborneD (1996) Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med334, 752–758.
5.
LandauSM, HarveyD, MadisonCM, KoeppeRA, ReimanEM, FosterNL, WeinerMW, JagustWJ, Initi AsDN (2009) Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging32, 1207–1218.
6.
de LeonMJ, ConvitA, WolfOT, TarshishCY, DeSantiS, RusinekH, TsuiW, KandilE, SchererAJ, RocheA, ImossiA, ThornE, BobinskiM, CaraosC, LesbreP, SchlyerD, PoirierJ, ReisbergB, FowlerJ (2001) Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET). Proc Natl Acad Sci U S A98, 10966–10971.
7.
SmallGW, ErcoliLM, SilvermanDH, HuangSC, KomoS, BookheimerSY, LavretskyH, MillerK, SiddarthP, RasgonNL, MazziottaJC, SaxenaS, WuHM, MegaMS, CummingsJL, SaundersAM, Pericak-VanceMA, RosesAD, BarrioJR, PhelpsME (2000) Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A97, 6037–6042.
8.
BrownBM, PeifferJJ, TaddeiK, LuiJK, LawsSM, GuptaVB, TaddeiT, WardVK, RodriguesMA, BurnhamS, Rainey-SmithSR, VillemagneVL, BushA, EllisKA, MastersCL, AmesD, MacaulaySL, SzoekeC, RoweCC, MartinsRN (2013) Physical activity and amyloid-beta plasma and brain levels: Results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing. Mol Psychiatry18, 875–881.
9.
SmithJC, NielsonKA, WoodardJL, SeidenbergM, DurgerianS, HazlettKE, FigueroaCM, KandahCC, KayCD, MatthewsMA, RaoSM (2014) Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer’s disease. Front Aging Neurosci6, 61.
MatthewsDC, DaviesM, MurrayJ, WilliamsS, TsuiWH, LiY, AndrewsRD, LukicA, McHughP, VallabhajosulaS, de LeonMJ, MosconiL (2014) Physical activity, Mediterranean diet and biomarkers-assessed risk of Alzheimer’s: A multi-modality brain imaging study. Adv J Mol Imaging4, 43–57.
12.
DyrstadSM, HansenBH, HolmeIM, AnderssenSA (2014) Comparison of self-reported versus accelerometer-measured physical activity. Med Sci Sports Exerc46, 99–106.
13.
BerlinJE, StortiKL, BrachJS (2006) Using activity monitors to measure physical activity in free-living conditions. Phys Ther86, 1137–1145.
14.
Celis-MoralesCA, Perez-BravoF, IbanezL, SalasC, BaileyME, GillJM (2012) Objective vs. self-reported physical activity and sedentary time: Effects of measurement method on relationships with risk biomarkers. PLoS One7, e36345.
15.
BuchmanAS, WilsonRS, BennettDA (2008) Total daily activity is associated with cognition in older persons. Am J Geriatr Psychiatry16, 697–701.
16.
ShephardRJ (2003) . Limits to the measurement of habitual physical activity by questionnaires. Br J Sports Med37, 197–206.
17.
SagerMA, HermannB, La RueA (2005) Middle-aged children of persons with Alzheimer’s disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer’s Prevention. J Geriatr Psychiatry Neurol18, 245–249.
18.
TroianoRP, BerriganD, DoddKW, MasseLC, TilertT, McDowellM (2008) Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc40, 181–188.
19.
LydenK, KeadleSK, StaudenmayerJ, FreedsonPS (2014) A method to estimate free-living active and sedentary behavior from an accelerometer. Med Sci Sports Exerc46, 386–397.
20.
StaudenmayerJ, PoberD, CrouterS, BassettD, FreedsonP (2009) An artificial neural network to estimate physical activity energy expenditure and identify physical activity type from an accelerometer. J Appl Physiol (1985)107, 1300–1307.
21.
JohnsonSC, ChristianBT, OkonkwoOC, OhJM, HardingS, XuGF, HillmerAT, WootenDW, MuraliD, BarnhartTE, HallLT, RacineAM, KlunkWE, MathisCA, BendlinBB, GallagherCL, CarlssonCM, RowleyHA, HermannBP, DowlingNM, AsthanaS, SagerMA (2014) Amyloid burden and neural function in people at risk for Alzheimer’s Disease. Neurobiol Aging35, 576–584.
FlobergJM, MistrettaCA, WeichertJP, HallLT, HoldenJE, ChristianBT (2012) Improved kinetic analysis of dynamic PET data with optimized HYPR-LR. Med Phys39, 3319–3331.
24.
JagustWJ, LandauSM, Alzheimer’s Disease Neuroimaging Initiative (2012) Apolipoprotein E, not fibrillar beta-amyloid, reduces cerebral glucose metabolism in normal aging. J Neurosci32, 18227–18233.
25.
EricksonKI, VossMW, PrakashRS, BasakC, SzaboA, ChaddockL, KimJS, HeoS, AlvesH, WhiteSM, WojcickiTR, MaileyE, VieiraVJ, MartinSA, PenceBD, WoodsJA, McAuleyE, KramerAF (2011) Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci U S A108, 3017–3022.
26.
VossMW, VivarC, KramerAF, van PraagH (2013) Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci17, 525–544.
27.
de LeonMJ, ConvitA, GeorgeAE, GolombJ, de SantiS, TarshishC, RusinekH, BobinskiM, InceC, MillerD, WisniewskiH (1996) Invivo structural studies of the hippocampus in normal agingand in incipient Alzheimer’s disease. Ann N Y Acad Sci777, 1–13.
28.
DuAT, SchuffN, AmendD, LaaksoMP, HsuYY, JagustWJ, YaffeK, KramerJH, ReedB, NormanD, ChuiHC, WeinerMW (2001) Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer’s disease. J Neurol Neurosurg Psychiatry71, 441–447.
29.
BallMJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study. Acta Neuropathol37, 111–118.
30.
Tzourio-MazoyerN, LandeauB, PapathanassiouD, CrivelloF, EtardO, DelcroixN, MazoyerB, JoliotM (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage15, 273–289.
31.
MaldjianJA, LaurientiPJ, KraftRA, BurdetteJH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage19, 1233–1239.
32.
OkonkwoOC, XuG, OhJM, DowlingNM, CarlssonCM, GallagherCL, BirdsillAC, PalottiM, WhartonW, HermannBP, LaRueA, BendlinBB, RowleyHA, AsthanaS, SagerMA, JohnsonSC (2014) Cerebral blood flow is diminished in asymptomatic middle-aged adults with maternal history of Alzheimer’s disease. Cereb Cortex24, 978–988.
33.
DoughertyRJ, EllingsonLD, SchultzSA, BootsEA, MeyerJD, LindheimerJB, Van RiperS, StegnerAJ, EdwardsDF, OhJM, KoscikRL, DowlingMN, GallagherCL, CarlssonCM, RowleyHA, BendlinBB, AsthanaS, HermannBP, SagerMA, JohnsonSC, OkonkwoOC, CookDB (2016) Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer’s disease. Alzheimers Dement (Amst)4, 14–17.
34.
DoughertyRJ, SchultzSA, BootsEA, EllingsonLD, MeyerJD, Van RiperS, StegnerAJ, EdwardsDF, OhJM, EinersonJ, KorcarzCE, KoscikRL, DowlingMN, GallagherCL, CarlssonCM, RowleyHA, BendlinBB, AsthanaS, HermannBP, SagerMA, SteinJH, JohnsonSC, OkonkwoOC, CookDB (2017) Relationships between cardiorespiratory fitness, hippocampal volume, and episodic memory in a population at risk for Alzheimer’s disease. Brain Behav7, e00625.
35.
BootsEA, SchultzSA, OhJM, LarsonJ, EdwardsD, CookD, KoscikRL, DowlingMN, GallagherCL, CarlssonCM, RowleyHA, BendlinBB, LaRueA, AsthanaS, HermannBP, SagerMA, JohnsonSC, OkonkwoOC (2015) Cardiorespiratory fitness is associated with brain structure, cognition, and mood in a middle-aged cohort at risk for Alzheimer’s disease. Brain Imaging Behav9, 639–649.
WilburJ, MarquezDX, FoggL, WilsonRS, StaffilenoBA, HoyemRL, MorrisMC, BustamanteEE, ManningAF (2012) The relationship between physical activity andcognition in older Latinos. J Gerontol B Psychol Sci Soc Sci67, 525–534.
45.
NelsonME, RejeskiWJ, BlairSN, DuncanPW, JudgeJO, KingAC, MaceraCA, Castaneda-SceppaC (2007) Physical activity and public health in older adults: Recommendation from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc39, 1435–1445.
PortoF, CoutinhoA, PintoA, GualanoB, DuranF, PrandoS, OnoC, SpindolaL, de OliveiraM, do ValeP, NitriniR, BuchpiguelC, BruckiS (2015) Effects of aerobic training on cognition and brain glucose metabolism in subjects with mild cognitive impairment. J Alzheimers Dis46, 747–760.
