Cognitive reserve (CR) has been postulated to contribute to the variation observed between neuropathology and clinical outcomes in Alzheimer’s disease (AD).
Objective:
We investigated the effect of an education-occupation derived CR proxy on biological properties of white matter tracts in patients with amnestic mild cognitive impairment (aMCI) and healthy elders (HC).
Methods:
Educational attainment and occupational complexity ratings (complexity with data, people, and things) from thirty-five patients with aMCI and twenty-eight HC were used to generate composite CR scores. Quantitative magnetic resonance imaging (qMRI) and multi-shell diffusion MRI were used to extract macromolecular tissue volume (MTV) across major white matter tracts.
Results:
We observed significant differences in the association between CR and white matter tract MTV in aMCI versus HC when age, gender, intracranial volume, and memory ability were held constant. Particularly, in aMCI, higher CR was associated with worse tract pathology (lower MTV) in the left and right dorsal cingulum, callosum forceps major, right inferior fronto-occipital fasciculus, and right superior longitudinal fasciculus (SLF) tracts. Conversely higher CR was associated with higher MTV in the right parahippocampal cingulum and left SLF in HC.
Conclusion:
Our results support compensatory CR mechanisms in aMCI and neuroprotective mechanisms in HC and suggest differential roles for CR on white matter macromolecular properties in healthy elders versus prodromal AD patients.
DeTureMA, DicksonDW (2019) The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener14, 32.
2.
KatzmanR, TerryR, DeTeresaR, BrownT, DaviesP, FuldP, RenbingX, PeckA (1988) Clinical, pathological, and neurochemical changes in dementia: A subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol23, 138–144.
3.
SteffenerJ, SternY (2012) Exploring the neural basis of cognitive reserve in aging. Biochim Biophys Acta1822, 467–473.
4.
MortimerJA (1997) Brain reserve and the clinical expression of Alzheimer’s disease. Geriatrics52, S50–S53.
5.
ValenzuelaMJ, SachdevP (2006) Brain reserve and dementia: A systematic review. Psychol Med36, 441–454.
6.
HabesM, GrotheMJ, TuncB, McMillanC, WolkDA, DavatzikosC (2020) Disentangling heterogeneity in Alzheimer’s disease and related dementias using data-driven methods. Biol Psychiatry88, 70–82.
7.
SternY (2012) Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol11, 1006–1012.
8.
SternY, BarnesCA, GradyC, JonesRN, RazN (2019) Brain reserve, cognitive reserve, compensation, and maintenance: Operationalization, validity, and mechanisms of cognitive resilience. Neurobiol Aging83, 124–129.
9.
BruandetA, RichardF, BomboisS, MaurageC, MasseI, AmouyelP, PasquierF (2008) Cognitive decline and survival in Alzheimer’s disease according to education level. Dement Geriatr Cogn Disord25, 74–80.
10.
GaribottoV, BorroniB, KalbeE, HerholzK, SalmonE, HoltoffV, SorbiS, CappaSF, PadovaniA, FazioF (2008) Education and occupation as proxies for reserve in aMCI converters and AD: FDG-PET evidence. Neurology71, 1342–1349.
11.
SternY, GurlandB, TatemichiTK, TangMX, WilderD, MayeuxR (1994) Influence of education and occupation on the incidence of Alzheimer’s disease. JAMA271, 1004–1010.
12.
WhalleyLJ, DearyIJ, AppletonCL, StarrJM (2004) Cognitive reserve and the neurobiology of cognitive aging. Ageing Res Rev3, 369–382.
13.
ZhangM, KatzmanR, SalmonD, JinH, CaiG, WangZ, QuG, GrantI, YuE, LevyP (1990) The prevalence of dementia and Alzheimer’s disease in Shanghai, China: Impact of age, gender, and education. Ann Neurol27, 428–437.
ZahodneLB, MayedaER, HohmanTJ, FletcherE, RacineAM, GavettB, ManlyJJ, SchupfN, MayeuxR, BrickmanAM (2019) The role of education in a vascular pathway to episodic memory: Brain maintenance or cognitive reserve? . Neurobiol Aging84, 109–118.
AnthonyM, LinF (2018) A systematic review for functional neuroimaging studies of cognitive reserve across the cognitive aging spectrum. Arch Clin Neuropsychol33, 937–948.
18.
BootsEA, SchultzSA, AlmeidaRP, OhJM, KoscikRL, DowlingMN, GallagherCL, CarlssonCM, RowleyHA, BendlinBB (2015) Occupational complexity and cognitive reserve in a middle-aged cohort at risk for Alzheimer’s disease. Arch Clin Neuropsychol30, 634–642.
19.
Arenaza-UrquijoEM, BoschB, Sala-LlonchR, Solé-PadullésC, JunquéC, Fernandez-EspejoD, BargalloN, RamiL, MolinuevoJL, Bartrés-FazD (2011) Specific anatomic associations between white matter integrity and cognitive reserve in normal and cognitively impaired elders. Am J Geriatr Psychiatry19, 33–42.
20.
Solé-PadullésC, Bartrés-FazD, JunquéC, VendrellP, RamiL, ClementeIC, BoschB, VillarA, BargallóN, JuradoMA (2009) Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging30, 1114–1124.
21.
TeipelSJ, MeindlT, WagnerM, KohlT, BürgerK, ReiserMF, HerpertzS, MöllerHJ, HampelH (2009) White matter microstructure in relation to education in aging and Alzheimer’s disease. J Alzheimers Dis17, 571–583.
22.
KaupAR, XiaF, LaunerLJ, SidneyS, NasrallahI, ErusG, AllenN, YaffeK (2018) Occupational cognitive complexity in earlier adulthood is associated with brain structure and cognitive health in midlife: The CARDIA study. Neuropsychology32, 895–905.
YeatmanJD, WandellBA, MezerAA (2014) Lifespan maturation and degeneration of human brain white matter. Nat Commun5, 4932.
26.
GozdasE, FingerhutH, ChromikLC, O’HaraR, ReissAL, HosseiniS (2020) Focal white matter disruptions along the cingulum tract explain cognitive decline in amnestic mild cognitive impairment (aMCI). Sci Rep10, 10213.
27.
GozdasE, FingerhutH, WuH, BrunoJL, DacorroL, JoB, O’HaraR, ReissAL, HosseiniSH (2021) Quantitative measurement of macromolecular tissue properties in white and gray matter in healthy aging and amnestic MCI. Neuroimage237, 118161.
28.
Delano-WoodL, StrickerNH, SorgSF, NationDA, JakAJ, WoodsSP, LibonDJ, DelisDC, FrankLR, BondiMW (2012) Posterior cingulum white matter disruption and its associations with verbal memory and stroke risk in mild cognitive impairment. J Alzheimers Dis29, 589–603.
29.
KimKW, MacFallJR, PayneME (2008) Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biol Psychiatry64, 273–280.
30.
PrinsND, ScheltensP (2015) White matter hyperintensities, cognitive impairment and dementia: An update. Nat Rev Neurol11, 157–165.
31.
WardlawJM, Valdés HernándezMC, Muñoz-ManiegaS (2015) What are white matter hyperintensities made of? Relevance to vascular cognitive impairment. J Am Heart Assoc4, e001140.
32.
BrickmanAM, ZahodneLB, GuzmanVA, NarkhedeA, MeierIB, GriffithEY, ProvenzanoFA, SchupfN, ManlyJJ, SternY (2015) Reconsidering harbingers of dementia: Progression of parietal lobe white matter hyperintensities predicts Alzheimer’s disease incidence. Neurobiol Aging36, 27–32.
TangX, CaiF, DingDX, ZhangLL, CaiXY, FangQ (2018) Magnetic resonance imaging relaxation time in Alzheimer’s disease. Brain Res Bull140, 176–189.
35.
MezerA, YeatmanJD, StikovN, KayKN, ChoNJ, DoughertyRF, PerryML, ParviziJ, HuaLH, Butts-PaulyK (2013) Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging. Nat Med19, 1667–1672.
36.
FiloS, ShtangelO, SalamonN, KolA, WeisingerB, ShifmanS, MezerAA (2019) Disentangling molecular alterations from water-content changes in the aging human brain using quantitative MRI. Nat Commun10, 3403.
37.
DeoniSC (2010) Quantitative relaxometry of the brain. Top Magn Reson Imaging21, 101–113.
38.
KalzendorfJ, BrueggenK, TeipelS (2020) Cognitive reserve is not associated with hippocampal microstructure in older adults without dementia. Front Aging Neurosci11, 380.
39.
SheehanDV, LecrubierY, SheehanKH, AmorimP, JanavsJ, WeillerE, HerguetaT, BakerR, DunbarGC (1998) The Mini-International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry59, 22–33.
40.
MontrossLP, DeppC, DalyJ, ReichstadtJ, GolshanS, MooreD, SitzerD, JesteDV (2006) Correlates of self-rated successful aging among community-dwelling older adults. Am J Geriatr Psychiatry14, 43–51.
41.
United States Employment Service (1991) Dictionary of occupational titles (4th ed.). U.S. Government Printing Office, Washington, DC.
JonaitisE, La RueA, MuellerKD, KoscikRL, HermannB, SagerMA (2013) Cognitive activities and cognitive performance in middle-aged adults at risk for Alzheimer’s disease. Psychol Aging28, 1004–1014.
44.
RoosPA, TreimanDJ (1980) Worker functions and worker traits for the 1970 US census classification. In Work, Jobs, and Occupations: A Critical Review of the Dictionary of Occupational Titles,Miller AR, Treiman DJ, Cain PS, Roos PA, eds. National Academy Press,Washington, DC, pp. 336–389.
45.
SternY, HabeckC, MoellerJ, ScarmeasN, AndersonKE, HiltonHJ, FlynnJ, SackeimH, Van HeertumR (2005) Brain networks associated with cognitive reserve in healthy young and old adults. Cereb Cortex15, 394–402.
46.
YeatmanJD, DoughertyRF, MyallNJ, WandellBA, FeldmanHM (2012) Tract profiles of white matter properties: Automating fiber-tract quantification. PloS One7, e49790.
47.
Arenaza-UrquijoEM, LandeauB, La JoieR, MevelK, MézengeF, PerrotinA, DesgrangesB, Bartrés-FazD, EustacheF, ChételatG (2013) Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders. Neuroimage83, 450–457.
48.
FratiglioniL, Paillard-BorgS, WinbladB (2004) An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol3, 343–353.
49.
GoldBT, JohnsonNF, PowellDK, SmithCD (2012) White matter integrity and vulnerability to Alzheimer’s disease: Preliminary findings and future directions. Biochim Biophys Acta1822, 416–422.
GreiciusMD, SupekarK, MenonV, DoughertyRF (2009) Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex19, 72–78.
52.
Andrews-HannaJR, SnyderAZ, VincentJL, LustigC, HeadD, RaichleME, BucknerRL (2007) Disruption of large-scale brain systems in advanced aging. Neuron56, 924–935.
53.
Bartrés-FazD, Solé-PadullésC, JunquéC, RamiL, BoschB, BargallóN, FalcónC, Sánchez-ValleR, MolinuevoJL (2009) Interactions of cognitive reserve with regional brain anatomy and brain function during a working memory task in healthy elders. Biol Psychol80, 256–259.
54.
BennettDA, WilsonR, SchneiderJ, EvansD, De LeonCM, ArnoldS, BarnesL, BieniasJ (2003) Education modifies the relation of AD pathology to level of cognitive function in older persons. Neurology60, 1909–1915.
55.
MenardiA, Pascual-LeoneA, FriedPJ, SantarnecchiE (2018) The role of cognitive reserve in Alzheimer’s disease and aging: A multi-modal imaging review. J Alzheimers Dis66, 1341–1362.
56.
SeoSW, ImK, LeeJM, KimST, AhnHJ, GoSM, KimSH, NaDL (2011) Effects of demographic factors on cortical thickness in Alzheimer’s disease. Neurobiol Aging32, 200–209.
57.
Wook YooS, HanCE, ShinJS, Won SeoS, NaDL, KaiserM, JeongY, SeongJK (2015) A network flow-based analysis of cognitive reserve in normal ageing and Alzheimer’s disease. Sci Rep5, 10057.
58.
HautMW, MoranMT, LancasterMA, KuwabaraH, ParsonsMW, PuceA (2007) White matter correlates of cognitive capacity studied with diffusion tensor imaging: Implications for cognitive reserve. Brain Imaging Behav1, 83–92.
ZatorreRJ, FieldsRD, Johansen-BergH (2012) Plasticity in gray and white: Neuroimaging changes in brain structure during learning. Nat Neurosci15, 528–536.
62.
DraganskiB, MayA (2008) Training-induced structural changes in the adult human brain. Behav Brain Res192, 137–142.
63.
MaillardP, SatizabalC, BeiserA, HimaliJ, ChenT, VasanR, SeshadriS, DeCarliC (2016) Effects of brain derived neurotrophic factor on white matter integrity in middle-aged adults: A voxel-based diffusion tensor imaging study. Neurology86, S39.006.
64.
AnatürkM, DemnitzN, EbmeierK, SextonC (2018) A systematic review and meta-analysis of structural magnetic resonance imaging studies investigating cognitive and social activity levels in older adults. Neurosci Biobehav Rev93, 71–84.
65.
JuraskaJM, KopcikJR (1988) Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Res450, 1–8.
ChapmanSB, AslanS, SpenceJS, HartJJJr, BartzEK, DidehbaniN, KeeblerMW, GardnerCM, StrainJF, DeFinaLF (2015) Neural mechanisms of brain plasticity with complex cognitive training in healthy seniors. Cereb Cortex25, 396–405.
68.
LongP, CorfasG (2014) Neuroscience. To learn is to myelinate. Science346, 298–299.
69.
ArfanakisK, WilsonRS, BarthCM, CapuanoAW, VasireddiA, ZhangS, FleischmanDA, BennettDA (2016) Cognitive activity, cognitive function, and brain diffusion characteristics in old age. Brain Imaging Behav10, 455–463.
70.
SoldanA, PettigrewC, AlbertM (2020) Cognitive reserve from the perspective of preclinical Alzheimer disease: 2020 update. Clin Geriatr Med36, 247–263.
71.
Arenaza-UrquijoEM, WirthM, ChételatG (2015) Cognitive reserve and lifestyle: Moving towards preclinical Alzheimer’s disease. Front Aging Neurosci7, 134.
72.
Bartrés-FazD, Arenaza-UrquijoEM (2011) Structural and functional imaging correlates of cognitive and brain reserve hypotheses in healthy and pathological aging. Brain Topogr24, 340–357.
73.
ValenzuelaM, BrayneC, SachdevP, WilcockG, MatthewsF; Medical Research Council Cognitive Function and Ageing Study (2011) Cognitive lifestyle and long-term risk of dementia and survival after diagnosis in a multicenter population-based cohort. Am J Epidemiol173, 1004–1012.
