Alzheimer's Disease-Related Metabolic Pattern in Diverse Forms of Neurodegenerative Diseases

Abstract

Dementia is broadly characterized by cognitive and psychological dysfunction that significantly impairs daily functioning. Dementia has many causes including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). Detection and differential diagnosis in the early stages of dementia remains challenging. Fueled by AD Neuroimaging Initiatives (ADNI) (Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. As such, the investigators within ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report.), a number of neuroimaging biomarkers for AD have been proposed, yet it remains to be seen whether these markers are also sensitive to other types of dementia. We assessed AD-related metabolic patterns in 27 patients with diverse forms of dementia (five had probable/possible AD while others had atypical cases) and 20 non-demented individuals. All participants had positron emission tomography (PET) scans on file. We used a pre-trained machine learning-based AD designation (MAD) framework to investigate the AD-related metabolic pattern among the participants under study. The MAD algorithm showed a sensitivity of 0.67 and specificity of 0.90 for distinguishing dementia patients from non-dementia participants. A total of 18/27 dementia patients and 2/20 non-dementia patients were identified as having AD-like patterns of metabolism. These results highlight that many underlying causes of dementia have similar hypometabolic pattern as AD and this similarity is an interesting avenue for future research.

Keywords: Alzheimer’s disease; FDG-PET; biomarker; dementia; dementia with Lewy bodies; frontotemporal lobar degeneration; machine learning; metabolic classification; neurodegenerative disease; support vector machine.

Figure 1

SVM scores generated by MAD in different test groups. A positive score means that MAD classified the subject’s FDG-PET brain image as similar to AD patients’ images. Undiff: Undifferentiated dementia; AD: Alzheimer’s disease; PCA: Posterior cortical atrophy; AAD: Atypical Alzheimer’s disease (frontal); DLB: Dementia with Lewy bodies; bvFTLD: Frontotemporal lobar degeneration, behavioural variant; PSP: Progressive supranuclear palsy; PPA: Primary progressive aphasia; Mixed: Mixed dementia (vascular + AD); MCI: Mild cognitive impairment; PPD: Primary psychiatric disorder; CH: Cognitively healthy.

Figure 2

Averaged FDG-PET brain images of different types of dementia. The FDG-PET images have been z-scored to the mean and standard deviation of 111 cognitively healthy individuals that were included in the training set of MAD derivation in our previous study [44], then averaged within each dementia type. Undiff: Undifferentiated dementia; AD: Alzheimer’s disease; PCA: Posterior cortical atrophy; AAD: Atypical Alzheimer’s disease (frontal); DLB: Dementia with Lewy bodies; bvFTLD: Frontotemporal lobar degeneration, behavioural variant; PSP: Progressive supranuclear palsy; PPA: Primary progressive aphasia; Mixed: Mixed dementia (vascular + AD); MCI: Mild cognitive impairment; PPD: Primary psychiatric disorder; CH: Cognitively healthy. The colour bar represents z value.