The alteration of the default mode network (DMN) functional connectivity (FC) has been reported in patients with amnestic mild cognitive impairment (aMCI) as a predictor of Alzheimer’s disease (AD). However, no studies exist that examined stage-dependent DMN FC changes throughout the course of aMCI. The present study aims to characterize patterns of DMN FC over three aMCI stages as first defined. Utilizing the extreme groups approach on the performance of memory tasks, aMCI subjects were divided into mild, moderate, and severe stages. Independent component analysis was used to assess DMN for individual patients in each of the three cross-sectionally defined stages. Instead of finding that continued monotonic decline was the case for the hippocampus volume, which we also investigated in this study, we observed an increase in DMN functional connectivity from mild aMCI to moderate aMCI and a decrease to severe aMCI, mainly in the left precuneus and superior parietal lobe. Moreover, the FC was significantly associated with cognitive performance. Though a longitudinal study is needed to confirm these results, our cross-sectional finding is that non-linear FC changes in DMN could be a characteristic of prodromal early disease development.
EwersM, SperlingRA, KlunkWE, WeinerMW, HampelH (2011) Neuroimaging markers for the prediction and early diagnosis of Alzheimer’s disease dementia. Trends Neurosci34, 430–442.
2.
PetersenR, StevensJ, GanguliM, TangalosE, CummingsJ, DeKoskyS (2001) Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology56, 1133–1142.
3.
BatschN, MittelmanM (2012) World Alzheimer Report 2012: Overcoming the stigma of dementia. Alzheimer’s Disease International.
4.
PetersenRC, StevensJC, GanguliM, TangalosEG, CummingsJL, DeKoskyST (2001) Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology56, 1133–1142.
5.
JackCR, KnopmanDS, JagustWJ, ShawLM, AisenPS, WeinerMW, PetersenRC, TrojanowskiJQ (2010) Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol9, 119–128.
6.
MorminoE, KluthJ, MadisonC, RabinoviciG, BakerS, MillerB, KoeppeR, MathisC, WeinerM, JagustW (2009) Episodic memory loss is related to hippocampal-mediated β-amyloid deposition in elderly subjects. Brain132, 1310–1323.
7.
SchuffN, TosunD, InselPS, ChiangGC, TruranD, AisenPS, JackCR, WeinerMW, Alzheimer’s Disease Neuroimaging Initiative (2012) Nonlinear time course of brain volume loss in cognitively normal and impaired elders. Neurobiol Aging33, 845–855.
8.
BozokiAC, KorolevIO, DavisNC, HoisingtonLA, BergerKL (2012) Disruption of limbic white matter pathways in mild cognitive impairment and Alzheimer’s disease: A DTI/FDG-PET Study. Hum Brain Mapp33, 1792–1802.
9.
LandauSM, HarveyD, MadisonCM, KoeppeRA, ReimanEM, FosterNL, WeinerMW, JagustWJ, Initiative AsDN (2011) Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging32, 1207–1218.
10.
SperlingRA, LaViolettePS, O’KeefeK, O’BrienJ, RentzDM, PihlajamakiM, MarshallG, HymanBT, SelkoeDJ, HeddenT (2009) Amyloid deposition is associated with impaired default network function in older persons without dementia. Neuron63, 178–188.
MosconiL (2005) Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease. Eur J Nucl Med Mol Imaging32, 486–510.
13.
DelbeuckX, Van der LindenM, ColletteF (2003) Alzheimer’s disease as a disconnection syndrome?Neuropsychol Rev13, 79–92.
14.
GreiciusMD, SrivastavaG, ReissAL, MenonV (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI. Proc Natl Acad Sci U S A101, 4637–4642.
15.
PetrellaJR, SheldonFC, PrinceSE, CalhounVD, DoraiswamyPM (2011) Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology76, 511–517.
16.
ShelineYI, RaichleME, SnyderAZ, MorrisJC, HeadD, WangS, MintunMA (2010) Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly. Biol Psychiatry67, 584–587.
17.
HeddenT, Van DijkKR, BeckerJA, MehtaA, SperlingRA, JohnsonKA, BucknerRL (2009) Disruption of functional connectivity in clinically normal older adults harboring amyloid burden. J Neurosci29, 12686–12694.
18.
GardiniS, VenneriA, SambataroF, CuetosF, FasanoF, MarchiM, CrisiG, CaffarraP (2015) Increased functional connectivity in the default mode network in mild cognitive impairment: A maladaptive compensatory mechanism associated with poor semantic memory performance. J Alzheimers Dis45, 457–470.
19.
QiZ, WuX, WangZ, ZhangN, DongH, YaoL, LiK (2010) Impairment and compensation coexist in amnestic MCI default mode network. Neuroimage50, 48–55.
20.
AisenPS, PetersenRC, DonohueMC, GamstA, RamanR, ThomasRG, WalterS, TrojanowskiJQ, ShawLM, BeckettLA (2010) Clinical core of the Alzheimer’s Disease Neuroimaging Initiative: Progress and plans. Alzheimers Dement6, 239–246.
21.
JessenF, WolfsgruberS, WieseB, BickelH, MöschE, KaduszkiewiczH, PentzekM, Riedel-HellerSG, LuckT, FuchsA, WeyererS, WerleJ, van den BusscheH, SchererM, MaierW, WagnerM; German Study on Aging, Cognition and Dementia in Primary Care Patients (2014) AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement10, 76–83.
22.
YeB, SeoS, YangJJ, KimH, KimY, YoonC, ChoH, NohY, KimG, ChinJ (2014) Comparison of cortical thickness in patients with early-stage versus late-stage amnestic mild cognitive impairment. Eur J Neurol21, 86–92.
23.
CeloneKA, CalhounVD, DickersonBC, AtriA, ChuaEF, MillerSL, DePeauK, RentzDM, SelkoeDJ, BlackerD (2006) Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: An independent component analysis. J Neurosci26, 10222–10231.
24.
BookheimerSY, StrojwasMH, CohenMS, SaundersAM, Pericak-VanceMA, MazziottaJC, SmallGW (2000) Patterns of brain activation in people at risk for Alzheimer’s disease. N Engl J Med343, 450–456.
25.
SchuffN, WoernerN, BoretaL, KornfieldT, ShawL, TrojanowskiJ, ThompsonP, JackC, WeinerM, Alzheimer’s Disease Nueroimaging Initiative (2009) MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain132, 1067–1077.
26.
LiX, MaC, ZhangJ, LiangY, ChenY, ChenK, WangJ, ZhangZ, WangY (2013) Prevalence of and potential risk factors for mild cognitive impairment in community-dwelling residents of Beijing. J Am Geriatr Soc61, 2111–2119.
27.
GuoQ (2007) Norm of auditory verbal learning test in the normal aged in China community. Chin J Clin Psychol15, 132.
28.
GuoQ (2006) Boston Naming Test in Chinese elderly, patient with mild cognitive impairment and Alzheimer’s dementia. Chin Ment Health J20, 81.
29.
ZhaoQ (2007) Supermarket verbal fluency test in identification and differential diagnosis of dementia. Chin J Clin Psychol15, 233.
30.
GuoQ, HongZ, LvC, ZhouY, LuJ, DingD (2005) Application of Stroop color-word test on Chinese elderly patients with mild cognitive impairment and mild Alzheimer’s dementia. Chin J Neuromed4, 701–704.
31.
GuoQ, ZhaoQ, ChenM, DingD, HongZ (2009) A comparison study of mild cognitive impairment with 3 memory tests among Chinese individuals. Alzheimer Dis Assoc Disord23, 253–259.
32.
ZhaoQ, DingD, GuoQ, MortimerJA, CopenhaverCI, SalmonD, GalaskoD, DeCarliC, DaiQ, PetersenR (2009) Shanghai community brain health initiative pilot study: Neuropsychological results. Alzheimers Dement5, P14–P15.
33.
RosenbergSJ, RyanJJ, PrifiteraA (1984) Rey Auditory-Verbal Learning Test performance of patients with and without memory impairment. J Clin Psychol40, 785–787.
34.
TuplerLA, WelshKA, Asare-AboagyeY, DawsonDV (1995) Reliability of the Rey-Osterrieth Complex Figure in use with memory-impaired patients. J Clin Exp Neuropsychol17, 566–579.
35.
PreacherKJ, RuckerDD, MacCallumRC, NicewanderWA (2005) Use of the extreme groups approach: A critical reexamination and new recommendations. Psychol Methods10, 178.
36.
GreiciusMD, SrivastavaG, ReissAL, MenonV (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: Evidence from functional MRI. Proc Natl Acad Sci U S A101, 4637–4642.
37.
PetrellaJ, SheldonF, PrinceS, CalhounV, DoraiswamyP (2011) Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology76, 511–517.
38.
HafkemeijerA, van der GrondJ, RomboutsSA (2012) Imaging the default mode network in aging and dementia. Biochim Biophys Acta1822, 431–441.
39.
BaiF, ZhangZ, YuH, ShiY, YuanY, ZhuW, ZhangX, QianY (2008) Default-mode network activity distinguishes amnestic type mild cognitive impairment from healthy aging: A combined structural and resting-state functional MRI study. Neurosci Lett438, 111–115.
IkonomovicM, KlunkW, AbrahamsonE, WuuJ, MathisC, ScheffS, MufsonE, DeKoskyS (2011) Precuneus amyloid burden is associated with reduced cholinergic activity in Alzheimer disease. Neurology77, 39–47.
47.
HeY, WangL, ZangY, TianL, ZhangX, LiK, JiangT (2007) Regional coherence changes in the early stages of Alzheimer’s disease: A combined structural and resting-state functional MRI study. Neuroimage35, 488–500.
48.
SorgC, RiedlV, MühlauM, CalhounVD, EicheleT, LäerL, DrzezgaA, FörstlH, KurzA, ZimmerC (2007) Selective changes of resting-state networks in individuals at risk for Alzheimer’s disease. Proc Natl Acad Sci U S A104, 18760–18765.
49.
CorbettaM, ShulmanGL, MiezinFM, PetersenSE (1995) Superior parietal cortex activation during spatial attention shifts and visual feature conjunction. Science270, 802–805.
50.
KoenigsM, BarbeyAK, PostleBR, GrafmanJ (2009) Superior parietal cortex is critical for the manipulation of information in working memory. J Neurosci29, 14980–14986.
