Cerebal Blood Flow Perfusion Patterns in Alzheimer's Disease

Aim: To determine if cerebral blood flow (CBF) perfusion patterns from arterial spin labeled magnetic resonance imaging (ASL-MR) is able to discriminate
mild-moderate Alzheimer's disease (AD) from healthy older controls and act as a potential biomarker in AD.

Methods: Pseudo-continuous ASL was used on a 3T HDx Signa GE scanner to investigate CBF perfusion. Seven subjects with probable Alzheimer's
disease (average age=72.0± 8.1 years, MMSE=19.3±4.7, range 13-26) and seven age and sex matched controls (average age=70.3± 6.4 years,
MMSE=29.1±1.2, range 27-30) had MRI scans including T1-weighted structural images and ASL-MR images. All subjects completed neuropsychological tests of global cognition including the Mini Mental Status Examination (MMSE), Montreal Cognitive Assessment scale (MoCA) anExamination and Alzheimer Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Whole brain CBF maps were obtained and transformed to a standard anatomical template for analysis. Principal Component Analysis (PCA), a method of multivariate analysis, detailed perfusion patterns of the data set as principal component images. The first component was used in every subject to examine differences between the two groups and relationships to the neuropsychological measures.

Results: The first principal component captured 27% of between group variation and demonstrated a perfusion pattern in which the AD group showed
regional hypo-perfusion relative to the control group in the parieto-occipital cortices, frontal cortices, posterior cingulate cortices and thalami (p=0.0403).

 

Fig 1. Each point indicates the expression of the first ASL-MR prinicpal component in each subject. Blue diamonds represent the AD group (n=7) and green circles indicate the control group (n=7). The mean of each group displayed is: AD=-0.148 and control=0.148.

 

 

 

Fig 2. Each point represents a measure of global cognition (red=MMSE, black=MoCA and green =ADAS-cog) as associated with expression of the first ASL-MR component. Increased severity of impairment as indexed by the MMSE, MoCA, and ADAS-cog appeared to be linearly associated with a decreased expression of the first component. There was no relationship among the controls, who showed ceiling or floor effects on each of the severity measures.

 

 

Fig 3. PCA demonstrated regional hypo-perfusion in the AD group relative to the control group in the parieto-occipital cortices, posterior cingulate cortices, frontal cortices , the left caudate head and thalami .

 

 

Fig 4. The generation of receiver operating characteristic (ROC) curves to differentiate the AD and control group using ASL-MR perfusion and neuropsychological tests of global cognition, reveals the ASL-MR perfusion data can differentiate the groups. With this small sample size, the neuropsychology data better predicts the presence of AD.

Discussion: The CBF pattern demonstrated in our small AD group was similar to previously established hypo-perfusion patterns of temporal, parietal and frontal cortices , posterior cingulate and thalami using PET (1) and MRI-ASL (2,3,4).

Conclusions: Arterial spin-labeled MRI is a new technique to investigate perfusion in AD. This technique is valid for discrimination between the AD and
control groups, and shows signs of correlation with cognitive impairment as indexed by neuropsychological measures. These preliminary results from a
larger ongoing study demonstrated the ability to detect differing patterns of perfusion, even with a small sample size. The ability to non-invasively acquire
high quality images and a quantitative measure of CBF, give ASL promise as a biomarker and in the study of future therapeutics in AD.

References
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This research is funded by the Neurological Foundation of New Zealand. The assistance of Dr Matthew Croucher in patient recruitment is gratefully acknowledged.