A preliminary study of cerebral blood flow, aging and dementia in people with Down syndrome.
Alzheimer's disease
Down syndrome
aging
cerebral blood flow
neuroimaging
Journal
Journal of intellectual disability research : JIDR
ISSN: 1365-2788
Titre abrégé: J Intellect Disabil Res
Pays: England
ID NLM: 9206090
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
31
01
2020
revised:
28
07
2020
accepted:
06
09
2020
pubmed:
1
10
2020
medline:
14
10
2021
entrez:
30
9
2020
Statut:
ppublish
Résumé
People with Down syndrome (DS) develop Alzheimer's disease (AD) at an earlier age of onset than those with sporadic AD. AD neuropathology is typically present in DS by 40 years of age with an onset of dementia approximately 10 years later. This early onset is due to the overexpression of amyloid precursor protein from the third copy of chromosome 21. Cerebrovascular neuropathology is thought to contribute in 40-60% of cases sporadic AD. However, the vascular contribution to dementia in people with DS has been relatively unexplored. We hypothesised that vascular perfusion is compromised in older adults with DS relative to younger individuals and is further exacerbated in those with dementia. Cerebral blood flow (CBF) was measured using pulsed arterial spin labelling in 35 cognitively characterised adults with DS (26-65 years). DS participants were also compared with 15 control subjects without DS or dementia (26-65 years). Linear regression evaluated the difference in CBF across groups and diagnosis along with assessing the association between CBF and cognitive measures within the DS cohort. Cerebral blood flow was significantly lower among DS participants with probable AD compared with controls (P = 0.02) and DS participants with no dementia (P = 0.01). Within the DS cohort, CBF was significantly associated with the Severe Impairment Battery (SIB) measure and the Dementia Questionnaire for People with Learning Disabilities (DLD) rating (F This preliminary study of CBF in DS indicates that cerebrovascular pathology may be a significant contributor to dementia in DS. CBF was associated with diagnosis, cognition and age. Notably, CBF decreases at a greater rate after age 45 and may represent a significant prodromal event in AD progression.
Sections du résumé
BACKGROUND
People with Down syndrome (DS) develop Alzheimer's disease (AD) at an earlier age of onset than those with sporadic AD. AD neuropathology is typically present in DS by 40 years of age with an onset of dementia approximately 10 years later. This early onset is due to the overexpression of amyloid precursor protein from the third copy of chromosome 21. Cerebrovascular neuropathology is thought to contribute in 40-60% of cases sporadic AD. However, the vascular contribution to dementia in people with DS has been relatively unexplored. We hypothesised that vascular perfusion is compromised in older adults with DS relative to younger individuals and is further exacerbated in those with dementia.
METHOD
Cerebral blood flow (CBF) was measured using pulsed arterial spin labelling in 35 cognitively characterised adults with DS (26-65 years). DS participants were also compared with 15 control subjects without DS or dementia (26-65 years). Linear regression evaluated the difference in CBF across groups and diagnosis along with assessing the association between CBF and cognitive measures within the DS cohort.
RESULTS
Cerebral blood flow was significantly lower among DS participants with probable AD compared with controls (P = 0.02) and DS participants with no dementia (P = 0.01). Within the DS cohort, CBF was significantly associated with the Severe Impairment Battery (SIB) measure and the Dementia Questionnaire for People with Learning Disabilities (DLD) rating (F
CONCLUSIONS
This preliminary study of CBF in DS indicates that cerebrovascular pathology may be a significant contributor to dementia in DS. CBF was associated with diagnosis, cognition and age. Notably, CBF decreases at a greater rate after age 45 and may represent a significant prodromal event in AD progression.
Identifiants
pubmed: 32996650
doi: 10.1111/jir.12784
pmc: PMC8244721
mid: NIHMS1710888
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
934-945Subventions
Organisme : NICHD NIH HHS
ID : R01 HD064993
Pays : United States
Organisme : NIH HHS
ID : S10 OD023573
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG057461
Pays : United States
Organisme : NIA NIH HHS
ID : U19 AG068054
Pays : United States
Informations de copyright
© 2020 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.
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