PMID- 34776436
OWN - NLM
STAT- MEDLINE
DCOM- 20220215
LR  - 20240323
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Print)
IS  - 1387-2877 (Linking)
VI  - 85
IP  - 1
DP  - 2022
TI  - Selective Impairment of Long-Range Default Mode Network Functional Connectivity 
      as a Biomarker for Preclinical Alzheimer's Disease in People with Down Syndrome.
PG  - 153-165
LID - 10.3233/JAD-210572 [doi]
AB  - BACKGROUND: Down syndrome (DS) is associated with increased risk for Alzheimer's 
      disease (AD). In neurotypical individuals, clinical AD is preceded by reduced 
      resting state functional connectivity in the default mode network (DMN), but it 
      is unknown whether changes in DMN connectivity predict clinical onset of AD in 
      DS. OBJECTIVE: Does lower DMN functional connectivity predict clinical onset of 
      AD and cognitive decline in people with DS? METHODS: Resting state functional MRI 
      (rsfMRI), longitudinal neuropsychological, and clinical assessment data were 
      collected on 15 nondemented people with DS (mean age = 51.66 years, SD = 5.34 
      years, range = 42-59 years) over four years, during which 4 transitioned to 
      dementia. Amyloid-beta (Abeta) PET data were acquired on 13 of the 15 participants. 
      Resting state fMRI, neuropsychological, and clinical assessment data were also 
      acquired on an independent, slightly younger unimpaired sample of 14 nondemented 
      people with DS (mean age = 44.63 years, SD = 7.99 years, range = 38-61 years). 
      RESULTS: Lower functional connectivity between long-range but not short-range DMN 
      regions predicts AD diagnosis and cognitive decline in people with DS. Abeta 
      accumulation in the inferior parietal cortex is associated with lower regional 
      DMN functional connectivity. CONCLUSION: Reduction of long-range DMN connectivity 
      is a potential biomarker for AD in people with DS that precedes and predicts 
      clinical conversion.
FAU - DiProspero, Natalie D
AU  - DiProspero ND
AD  - Department of Neurobiology and Behavior, University of California, Irvine, CA, 
      USA.
AD  - Center for the Neurobiology of Learning and Memory, University of California, 
      Irvine, CA, USA.
FAU - Keator, David B
AU  - Keator DB
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine, 
      CA, USA.
FAU - Phelan, Michael
AU  - Phelan M
AD  - Institute for Memory Impairments and Neurological Disorders, UC Irvine, CA, USA.
FAU - van Erp, Theo G M
AU  - van Erp TGM
AD  - Department of Pediatrics, University of California, Irvine Medical Center, 
      Orange, CA, USA.
FAU - Doran, Eric
AU  - Doran E
AD  - Department of Pediatrics, University of California, Irvine Medical Center, 
      Orange, CA, USA.
FAU - Powell, David K
AU  - Powell DK
AD  - Department of Neuroscience, University of Kentucky Medical Center, Lexington, KY, 
      USA.
FAU - Van Pelt, Kathryn L
AU  - Van Pelt KL
AD  - Sanders-Brown Center on Aging, University of Kentucky Medical Center, Lexington, 
      KY, USA.
FAU - Schmitt, Frederick A
AU  - Schmitt FA
AD  - Sanders-Brown Center on Aging, University of Kentucky Medical Center, Lexington, 
      KY, USA.
AD  - Department of Neurology, University of Kentucky Medical Center, Lexington, KY, 
      USA.
FAU - Head, Elizabeth
AU  - Head E
AD  - Department of Pathology and Laboratory Medicine, University of California, 
      Irvine, CA, USA.
FAU - Lott, Ira T
AU  - Lott IT
AD  - Department of Pediatrics, University of California, Irvine Medical Center, 
      Orange, CA, USA.
FAU - Yassa, Michael A
AU  - Yassa MA
AD  - Department of Neurobiology and Behavior, University of California, Irvine, CA, 
      USA.
AD  - Center for the Neurobiology of Learning and Memory, University of California, 
      Irvine, CA, USA.
AD  - Department of Psychiatry and Human Behavior, University of California, Irvine, 
      CA, USA.
LA  - eng
GR  - P30 AG072946/AG/NIA NIH HHS/United States
GR  - R01 AG053555/AG/NIA NIH HHS/United States
GR  - U24 AG021886/AG/NIA NIH HHS/United States
GR  - R01 HD064993/HD/NICHD NIH HHS/United States
GR  - U01 AG051412/AG/NIA NIH HHS/United States
GR  - T32 AG000096/AG/NIA NIH HHS/United States
GR  - R01 HD065160/HD/NICHD NIH HHS/United States
GR  - P30 AG066519/AG/NIA NIH HHS/United States
GR  - U19 AG068054/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Biomarkers)
SB  - IM
MH  - Alzheimer Disease/*complications/diagnostic imaging
MH  - Biomarkers
MH  - Brain/diagnostic imaging/*physiopathology
MH  - Cognitive Dysfunction/*complications/diagnostic imaging
MH  - Default Mode Network/diagnostic imaging/*physiopathology
MH  - Down Syndrome/*complications/diagnostic imaging
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Positron-Emission Tomography
PMC - PMC9017677
MID - NIHMS1788995
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Down syndrome
OT  - biomarkers
OT  - default mode network
OT  - dementia
OT  - functional connectivity
OT  - resting state functional magnetic resonance imaging
COIS- CONFLICT OF INTEREST The authors certify that they have no affiliations with or 
      involvement in any organization or entity with any financial interest, or 
      non-financial interest in the subject matter or materials discussed in this 
      article.
EDAT- 2021/11/16 06:00
MHDA- 2022/02/16 06:00
PMCR- 2023/01/01
CRDT- 2021/11/15 06:46
PHST- 2021/11/16 06:00 [pubmed]
PHST- 2022/02/16 06:00 [medline]
PHST- 2021/11/15 06:46 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - JAD210572 [pii]
AID - 10.3233/JAD-210572 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2022;85(1):153-165. doi: 10.3233/JAD-210572.