Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease.
BACKGROUND
We examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning.


METHODS
Thirty-two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (PtO2).


RESULTS
At baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low PtO2across the cortex. Cognitive decline over time was associated with increasing whole brain relative transit time heterogeneity (RTH = CTH/MTT).


CONCLUSIONS
Our results confirm the importance of microvascular pathology in AD. Deteriorating microvascular hemodynamics may cause hypoxia, which is known to precipitate amyloid retention.
Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark. Electronic address: rbaeksager@cfin.au.dk.
Rune B
RB
Nielsen
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Lærke
L
Egefjord
Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
Hugo
H
Angleys
Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
Kim
K
Mouridsen
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Michael
M
Gejl
PET-Center, Department of Nuclear Medicine, Aarhus University Hospital, Aarhus, Denmark.
Arne
A
Møller
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Birgitte
B
Brock
Dementia Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
Hans
H
Brændgaard
Dementia Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
Hanne
H
Gottrup
Department of Endocrinology, Bispebjerg University Hospital, Copenhagen, Denmark.
Jørgen
J
Rungby
Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark.
Simon F
SF
Eskildsen
Center of Functionally Integrative Neuroscience and MINDLab, Aarhus University, Aarhus, Denmark; Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark.
Leif
L
Østergaard
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology*; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D055806:Microvessels / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000209:etiology*; D009483:Neuropsychological Tests; D010477:Perfusion
Alzheimer's disease; Capillary dysfunction; Capillary transit time heterogeneity (CTH); Cerebral blood flow (CBF); Cerebral blood volume (CBV); Cortical thinning; Hypoxia; Magnetic resonance imaging (MRI); Microvascular dysfunction; Neurodegeneration; Neurovascular dysfunction; Perfusion imaging; Relative transit time heterogeneity (RTH); Tissue oxygen tension (P(t)O(2))