Restricted accessResearch articleFirst published online 2016-8-3
Adults at Increased Alzheimer’s Disease Risk Display Cognitive-Motor Integration Impairment Associated with Changes in Resting-State Functional Connectivity: A Preliminary Study
Background: Many neuroimaging parameters have demonstrated utility as
biomarkers in preclinical AD, including resting-state functional connectivity in the
default mode network. However, neuroimaging is not a practical, cost effective screening
instrument.
Objective: Here we investigate the relationship between performance on a
cognitive-motor integration assessment and alterations in resting-state functional
connectivity in an at-risk population.
Methods: Three groups of ten adults (young: mean age = 26.6 ± 2.7, low AD
risk: mean age = 58.7 ± 5.6, and high AD risk: mean age = 58.5 ± 6.9) performed a simple
cognitive-motor integration task using a dual-touchscreen laptop and also underwent
functional magnetic resonance imaging at rest.
Results: We found poorer cognitive-motor integration performance in high AD
risk participants, as well as an association with lower resting-state functional
connectivity in this group.
Conclusion: These findings provide novel insight into underlying AD-related
brain alterations associated with a behavioral assessment that can be easily administered
clinically.
EwersM, SperlingRA, KlunkWE, WeinerMW, HampelH
(2011) Neuroimaging markers for the prediction and early
diagnosis of Alzheimer’s disease dementia. Trends
Neurosci34, 430–442.
2.
LiuCC, KanekiyoT, XuH,
BuG (2013)
Apolipoprotein E and Alzheimer disease: Risk, mechanisms and
therapy. Nat Rev9, 106–118.
3.
FratiglioniL,
AhlbomA, ViitanenM, WinbladB
(1993) Risk factors for late-onset Alzheimer’s disease: A
population-based, case-control study. Ann Neurol33, 258–266.
4.
GreenRC, CupplesLA, GoR,
BenkeKS, EdekiT,
GriffithPA, WilliamsM, HippsY,
Graff-RadfordN,
BachmanD, FarrerLA, MIRAGEStudy
Group (2002) Risk of dementia
among white and African American relatives of patients with Alzheimer
disease. JAMA287, 329–336.
5.
MayeuxR, SanoM,
ChenJ, TatemichiT, SternY
(1991) Risk of dementia in first-degree relatives of
patients with Alzheimer’s disease and related disorders. Arch
Neurol48, 269–273.
6.
StorandtM, MintunMA, HeadD,
MorrisJC
(2009) Cognitive decline and brain volume loss as signatures
of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B:
Cognitive decline associated with Abeta deposition. Arch
Neurol66, 1476–1481.
7.
MitchellJ, ArnoldR, DawsonK, NestorPJ, HodgesJR
(2009) Outcome in subgroups of mild cognitive impairment (MCI)
is highly predictable using a simple algorithm. J
Neurol256, 1500–1509.
8.
AgostaF, PievaniM, GeroldiC, CopettiM, FrisoniGB, FilippiM
(2012) Resting state fMRI in Alzheimer’s disease: Beyond the
default mode network. Neurobiol Aging33, 1564–1578.
9.
LiuY, YuC,
ZhangX, LiuJ,
DuanY, Alexander-BlochAF,
LiuB, JiangT,
BullmoreE
(2014) Impaired long distance functional connectivity and
weighted network architecture in Alzheimer’s disease. Cereb
Cortex24, 1422–1435.
10.
BartzokisG, SultzerD, LuPH,
NuechterleinKH,
MintzJ, CummingsJL
(2004) Heterogeneous age-related breakdown of white matter
structural integrity: Implications for cortical “disconnection” in aging and Alzheimer’s
disease. Neurobiol Aging25, 843–851.
11.
BartzokisG
(2004) Age-related myelin breakdown: A developmental model
of cognitive decline and Alzheimer’s disease. Neurobiol
Aging25, 5–18.
12.
GoldBT, PowellDK, AndersenAH, SmithCD
(2010) Alterations in multiple measures of white matter
integrity in normal women at high risk for Alzheimer’s disease.
Neuroimage52, 1487–1494.
13.
PerssonJ, LindJ,
LarssonA, IngvarM, CrutsM,
Van
BroeckhovenC, AdolfssonR, NilssonLG, NybergL
(2006) Altered brain white matter integrity in healthy
carriers of the APOE epsilon4 allele: A risk for AD?Neurology66, 1029–1033.
14.
ReisbergB, FranssenEH, SourenLE, AuerSR,
AkramI, KenowskyS
(2002) Evidence and mechanisms of retrogenesis in
Alzheimer’s and other dementias: Management and treatment import.
Am J Alzheimers Dis Other Demen17, 202–212.
15.
SmithCD, ChebroluH, AndersenAH, PowellDA, LovellMA, XiongS,
GoldBT (2010)
White matter diffusion alterations in normal women at risk of Alzheimer’s
disease. Neurobiol Aging31, 1122–1131.
16.
BonniS, LupoF,
Lo
GerfoE, MartoranaA, PerriR,
CaltagironeC,
KochG (2013)
Altered parietal-motor connections in Alzheimer’s disease
patients. J Alzheimers Dis33, 525–533.
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.
MorminoEC, SmiljicA, HayengaAO, OnamiSH, GreiciusMD, RabinoviciGD, JanabiM, BakerSL, YenIV,
MadisonCM, MillerBL, JagustWJ
(2011) Relationships between beta-amyloid and functional
connectivity in different components of the default mode network in
aging. Cereb Cortex21, 2399–2407.
19.
PetrellaJR, SheldonFC, PrinceSE, CalhounVD, DoraiswamyPM
(2011) Default mode network connectivity in stable vs
progressive mild cognitive impairment. Neurology76, 511–517.
20.
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.
21.
ShelineYI, MorrisJC, SnyderAZ, PriceJL, YanZ,
D’AngeloG, LiuC,
DixitS, BenzingerT, FaganA,
GoateA, MintunMA
(2010) APOE4 allele disrupts resting state fMRI connectivity
in the absence of amyloid plaques or decreased CSF Abeta42. J
Neurosci30, 17035–17040.
22.
SorgC, RiedlV,
MuhlauM, CalhounVD, EicheleT, LaerL,
DrzezgaA, ForstlH, KurzA,
ZimmerC, WohlschlagerAM
(2007) Selective changes of resting-state networks in
individuals at risk for Alzheimer’s disease. Proc Natl Acad Sci
U S A104, 18760–18765.
23.
de
BoerC, Mattace-RasoF, van der
SteenJ, PelJJ
(2013) Mini-Mental State Examination subscores indicate
visuomotor deficits in Alzheimer’s disease patients: A cross-sectional study in a Dutch
population. Geriatr Gerontol Int14, 880–885.
24.
GhilardiMF, AlberoniM, MarelliS, RossiM,
FranceschiM, GhezC,
FazioF (1999)
Impaired movement control in Alzheimer’s disease.
Neurosci Lett260, 45–48.
25.
GhilardiMF, AlberoniM, RossiM,
FranceschiM, MarianiC, FazioF
(2000) Visual feedback has differential effects on reaching
movements in Parkinson’s and Alzheimer’s disease. Brain
Res876, 112–123.
26.
HawkinsKM, SergioLE
(2014) Visuomotor impairments in older adults at increased
Alzheimer’s disease risk. J Alzheimers Dis42, 607–621.
27.
SalekY, AndersonND, SergioL
(2011) Mild cognitive impairment is associated with impaired
visual-motor planning when visual stimuli and actions are incongruent.
Eur Neurol66, 283–293.
28.
TippettWJ, SergioLE
(2006) Visuomotor integration is impaired in early stage
Alzheimer’s disease. Brain Res1102, 92–102.
29.
TippettWJ, KrajewskiA, SergioLE
(2007) Visuomotor integration is compromised in Alzheimer’s
disease patients reaching for remembered targets. Eur
Neurol58, 1–11.
30.
TippettWJ, SergioLE, BlackSE
(2012) Compromised visually guided motor control in
individuals with Alzheimer’s disease: Can reliable distinctions be
observed?J Clin Neurosci19, 655–660.
31.
VerheijS, MuilwijkD, PelJJ,
van der
CammenTJ, Mattace-RasoFU,
van der
SteenJ (2012)
Visuomotor impairment in early-stage Alzheimer’s disease: Changes in
relative timing of eye and hand movements. J Alzheimers
Dis30, 131–143.
32.
HawkinsKM, GoyalAI, SergioLE
(2015) Diffusion tensor imaging correlates of cognitive-motor
decline in normal aging and increased Alzheimer’s disease risk.
J Alzheimers Dis44, 867–878.
33.
CarterCL, ResnickEM, MallampalliM, KalbarczykA
(2012) Sex and gender differences in Alzheimer’s disease:
Recommendations for future research. J Womens Health21, 1018–1023.
ReillySL, FerrellRE, SingCF
(1994) The gender-specific apolipoprotein E genotype
influence on the distribution of plasma lipids and apolipoproteins in the population of
Rochester, MN. III. Correlations and covariances. Am J Hum
Genet55, 1001–1018.
36.
HoneaRA, SwerdlowRH, VidoniED, BurnsJM
(2011) Progressive regional atrophy in normal adults with a
maternal history of Alzheimer disease. Neurology76, 822–829.
37.
MosconiL, BrysM,
SwitalskiR, MisturR, GlodzikL, PirragliaE, TsuiW,
De
SantiS, de
LeonMJ (2007)
Maternal family history of Alzheimer’s disease predisposes to reduced
brain glucose metabolism. Proc Natl Acad Sci U S A104, 19067–19072.
38.
MosconiL, GlodzikL, MisturR, McHughP, RichKE,
JavierE, WilliamsS, PirragliaE, De
SantiS, MehtaPD, ZinkowskiR, BlennowK, PraticoD, de
LeonMJ (2010)
Oxidative stress and amyloid-beta pathology in normal individuals with a
maternal history of Alzheimer’s. Biol Psychiatry68, 913–921.
FilippiniN, MacIntoshBJ, HoughMG, GoodwinGM, FrisoniGB, SmithSM, MatthewsPM, BeckmannCF, MackayCE
(2009) Distinct patterns of brain activity in young carriers
of the APOE-epsilon4 allele. Proc Natl Acad Sci U S A106, 7209–7214.
41.
JenkinsonM, BannisterP, BradyM,
SmithS (2002)
Improved optimization for the robust and accurate linear registration and
motion correction of brain images. Neuroimage17, 825–841.
BiswalB, YetkinFZ, HaughtonVM, HydeJS
(1995) Functional connectivity in the motor cortex of
resting human brain using echo-planar MRI. Magn Reson
Med34, 537–541.
44.
ZhangY, BradyM,
SmithS (2001)
Segmentation of brain MR images through a hidden Markov random field
model and the expectation-maximization algorithm. IEEE Trans Med
Imaging20, 45–57.
45.
RaichleME, MacLeodAM, SnyderAZ, PowersWJ, GusnardDA, ShulmanGL
(2001) A default mode of brain function.
Proc Natl Acad Sci U S A98, 676–682.
46.
DrzezgaA, BeckerJA, Van
DijkKR, SreenivasanA, TalukdarT, SullivanC, SchultzAP, SepulcreJ, PutchaD, GreveD,
JohnsonKA, SperlingRA
(2011) Neuronal dysfunction and disconnection of cortical
hubs in non-demented subjects with elevated amyloid burden.
Brain134, 1635–1646.
Battaglia-MayerA,
FerrainaS, MitsudaT, MarconiB, GenovesioA, OnoratiP, LacquanitiF, CaminitiR
(2000) Early coding of reaching in the parietooccipital
cortex. J Neurophysiol83, 2374–2391.
49.
GalatiG, CommitteriG, PitzalisS, PelleG,
PatriaF, FattoriP, GallettiC
(2011) Intentional signals during saccadic and reaching
delays in the human posterior parietal cortex. Eur J
Neurosci34, 1871–1885.
50.
HawkinsKM, SayeghP, YanX,
CrawfordJD, SergioLE
(2013) Neural activity in superior parietal cortex during
rule-based visual-motor transformations. J Cogn
Neurosci25, 436–454.
51.
ShaoY, WangL,
YeE, JinX,
NiW, YangY,
WenB, HuD,
YangZ (2013)
Decreased thalamocortical functional connectivity after 36 hours of total
sleep deprivation: Evidence from resting state FMRI. PLoS
One8, e78830.
52.
MiddletonFA, StrickPL
(2000) Basal ganglia and cerebellar loops: Motor and cognitive
circuits. Brain Res Brain Res Rev31, 236–250.
53.
LeismanG, Braun-BenjaminO,
MelilloR
(2014) Cognitive-motor interactions of the basal ganglia in
development. Front Syst Neurosci8, 16–.
54.
ReigR, SilberbergG
(2014) Multisensory integration in the mouse
striatum. Neuron83, 1200–1212.
