Cross-sectional studies have shown lower cerebral blood flow (CBF) in Alzheimer’s disease (AD), but longitudinal CBF changes in AD are still unknown.
Objective:
To reveal the longitudinal CBF changes in normal control (NC) and the AD continuum using arterial spin labeling perfusion magnetic resonance imaging (ASL MRI).
Methods:
CBF was calculated from two longitudinal ASL scans acquired 2.22±1.43 years apart from 140 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). At the baseline scan, the cohort contained 41 NC, 74 mild cognitive impairment patients (MCI), and 25 AD patients. 21 NC converted into MCI and 17 MCI converted into AD at the follow-up. Longitudinal CBF changes were assessed using paired-t test for non-converters and converters separately at each voxel and in the meta-ROI. Age and sex were used as covariates.
Results:
CBF reductions were observed in all subjects. Stable NC (n = 20) showed CBF reduction in the hippocampus and precuneus. Stable MCI patients (n = 57) showed spatially more extended CBF reduction patterns in hippocampus, middle temporal lobe, ventral striatum, prefrontal cortex, and cerebellum. NC-MCI converters showed CBF reduction in hippocampus and cerebellum and CBF increase in caudate. MCI-AD converters showed CBF reduction in hippocampus and prefrontal cortex. CBF changes were not related with longitudinal neurocognitive changes.
Conclusion:
Normal aging and AD continuum showed common longitudinal CBF reductions in hippocampus independent of disease and its conversion. Disease conversion independent longitudinal CBF reductions escalated in MCI subjects.
SperlingRA, AisenPS, BeckettLA, BennettDA, CraftS, FaganAM, IwatsuboT, JackCRJr, KayeJ, MontineTJ, ParkDC, ReimanEM, RoweCC, SiemersE, SternY, YaffeK, CarrilloMC, ThiesB, Morrison-BogoradM, WagsterMV, PhelpsCH (2011) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 280–292.
AlsopDC, DetreJA, GrossmanM (2000) Assessment of cerebral blood flow in Alzheimer’s disease by spin-labeled magnetic resonance imaging. . Ann Neurol47, 93–100.
4.
WolkDA, DetreJA (2012) Arterial spin labeling MRI: an emerging biomarker for Alzheimer’s disease and other neurodegenerative conditions. . Curr Opin Neurol25, 421–428.
WilliamsDS, DetreJA, LeighJS, KoretskyAP (1992) Magnetic resonance imaging of perfusion using spin inversion of arterial water. Proc Natl Acad Sci U S A89, 212–216. Erratum in: Proc Natl Acad Sci U S A 1992 May 1;89(9):4220.
ZhangQ, StaffordRB, WangZ, ArnoldSE, WolkDA, DetreJA (2012) Microvascular perfusion based on arterial spin labeled perfusion MRI as a measure of vascular risk in Alzheimer’s disease. . J Alzheimers Dis32, 677–687.
12.
AlexopoulosP, SorgC, FörschlerA, GrimmerT, SkokouM, WohlschlägerA, PerneczkyR, ZimmerC, KurzA, PreibischC (2012) Perfusion abnormalities in mild cognitive impairment and mild dementia in Alzheimer’s disease measured by pulsed arterial spin labeling MRI. . Eur Arch Psychiatry Clin Neurosci262, 69–77.
13.
WangZ (2016) Longitudinal CBF changes predict disease conversion/revision in AD and MCI. The 22nd Annual Meeting of the Organization for Human Brain Mapping, Geneva, Switzerland, #1009.
14.
StaffaroniAM, CobigoY, ElahiFM, CasalettoKB, WaltersSM, WolfA, LindberghCA, RosenHJ, KramerJH (2019) A longitudinal characterization of perfusion in the aging brain and associations with cognition and neural structure. Hum Brain Mapp40, 3522–3533.
15.
LuhWM, WongEC, BandettiniPA, HydeJS (1999) QUIPSS II with thin-slice TI1 periodic saturation: A method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling. . Magn Reson Med41, 1246–1254.
16.
WangZ, AguirreGK, RaoH, WangJ, Fernández-SearaMA, ChildressAR, DetreJA (2008) Empirical optimization of ASL data analysis using an ASL data processing toolbox: ASLtbx. . Magn Reson Imaging26, 261–269.
17.
WangZ (2012) Improving cerebral blood flow quantification for arterial spin labeled perfusion MRI by removing residual motion artifacts and global signal fluctuations magnetic resonance imaging. . Magn Reson Med30, 1409–1415.
BuxtonRB, FrankLR, WongEC, SiewertB, WarachS, EdelmanRR (1998) A general kinetic model for quantitative perfusion imaging with arterial spin labeling. . Magn Reson Med40, 383–396.
PerryRJ, HodgesJR (1999) Attention and executive deficits in Alzheimer’s disease. A critical review. Brain122, 383–404.
27.
MurrayME, Graff-RadfordNR, RossOA, PetersenRC, DuaraR, DicksonDW (2011) Neuropathologically defined subtypes of Alzheimer’s disease with distinct clinical characteristics: A retrospective study. . Lancet Neurol10, 785–796.
28.
GutchessAH, WelshRC, BodurogluA, ParkDC (2006) Cultural differences in neural function associated with object processing. . Cogn Affect Behav Neurosci6, 102–109.
HaberSN (2011) Neuroanatomy of reward: a view from the ventral striatum. In Neurobiology of Sensation and Reward, Gottfried JA, ed. CRC Press/Taylor & Francis, Boca Raton, FL, Chapter 11.
31.
DreherJC, Meyer-LindenbergA, KohnP, BermanKF (2008) Age-related changes in midbrain dopaminergic regulation of the human reward system. . Proc Natl Acad Sci U S A105, 15106–15111.
32.
RazN, RodrigueKM, KennedyKM, HeadD, Gunning-DixonF, AckerJD (2003) Differential aging of the human striatum: Longitudinal evidence. . AJNR Am J Neuroradiol24, 1849–1856.
33.
ChoH, KimJH, KimC, YeBS, KimHJ, YoonCW, NohY, KimGH, KimYJ, KimJH, KimCH, KangSJ, ChinJ, KimST, LeeKH, NaDL, SeongJK, SeoSW (2014) Shape changes of the basal ganglia and thalamus in Alzheimer’s disease: A three-year longitudinal study. . J Alzheimers Dis40, 285–295.
34.
DoluiS, LiZ, NasrallahIM, DetreJA, WolkDA (2020) Arterial spin labeling versus 18F-FDG-PET to identify mild cognitive impairment. . Neuroimage Clin25, 102146.
35.
MusiekES, ChenY, KorczykowskiM, SabouryB, MartinezPM, ReddinJS, AlaviA, KimbergDY, WolkDA, JulinP, NewbergAB, ArnoldSE, DetreJA (2012) Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer’s disease. . Alzheimers Dement8, 51–59.
36.
KuwabaraY, IchiyaY, IchimiyaA, SasakiM, AkashiY, YoshidaT, FukumuraT, MasudaK (1994) A longitudinal study of CMRGlu in dementia of Alzheimer type [Japanese]. . Kaku Igaku31, 1255–1260.
37.
LeeHG, CasadesusG, ZhuX, TakedaA, PerryG, SmithMA (2004) Challenging the amyloid cascade hypothesis: Senile plaques and amyloid-beta as protective adaptations to Alzheimer disease. . Ann N Y Acad Sci1019, 1–4.
38.
TseKH, HerrupK (2017) Re-imagining Alzheimer’s disease - the diminishing importance of amyloid and a glimpse of what lies ahead. . J Neurochem143, 432–444.
39.
ZhuX, LeeHG, PerryG, SmithMA (2007) Alzheimer disease, the two-hit hypothesis: an update. . Biochim Biophys Acta1772, 494–502.
40.
ZlokovicBV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. . Nat Rev Neurosci12, 723–738.
41.
DeiblerAR, PollockJM, KraftRA, TanH, BurdetteJH, MaldjianJA (2008) Arterial spin-labeling in routine clinical practice, part 2: Hypoperfusion patterns. . AJNR Am J Neuroradiol29, 1235–1241.
