Neuroimaging and other modalities to assess Alzheimer's disease in Down syndrome

Abstract

People with Down syndrome (DS) develop Alzheimer's disease (AD) at higher rates and a younger age of onset compared to the general population. As the average lifespan of people with DS is increasing, AD is becoming an important health concern in this group. Neuroimaging is becoming an increasingly useful tool in understanding the pathogenesis of dementia development in relation to clinical symptoms. Furthermore, neuroimaging has the potential to play a role in AD diagnosis and monitoring of therapeutics. This review describes major recent findings from in vivo neuroimaging studies analysing DS and AD via ligand-based positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG)-PET, structural magnetic resonance imaging (sMRI), and diffusion tensor imaging (DTI). Electroencephalography (EEG) and retinal imaging are also discussed as emerging modalities. The review is organized by neuroimaging method and assesses the relationship between cognitive decline and neuroimaging changes. We find that amyloid accumulation seen on PET occurs prior to dementia onset, possibly as a precursor to the atrophy and white matter changes seen in MRI studies. Future PET studies relating tau distribution to clinical symptoms will provide further insight into the role this protein plays in dementia development. Brain activity changes demonstrated by EEG and metabolic changes seen via FDG-PET may also follow predictable patterns that can help track dementia progression. Finally, newer approaches such as retinal imaging will hopefully overcome some of the limitations of neuroimaging and allow for detection of dementia at an earlier stage.

New approaches to studying early brain development in Down syndrome

“…Quantitative early MRI data could be related to data derived from clinical, cognitive, and behavioural assessments, as well as genetic information, thus allowing a comprehensive understanding of the complex relationships which underpin the Down syndrome phenotype. Such studies are currently ongoing in adults with Down syndrome to assess the changes in brain structure and function associated with cognitive decline and progression into early onset Alzheimer disease …”

“…Such studies are currently ongoing in adults with Down syndrome to assess the changes in brain structure and function associated with cognitive decline and progression into early onset Alzheimer disease. 86…”

Neuropathological correlates of amyloid PET imaging in Down syndrome

“…In DS subjects aged >40 years, levels of cortical Aβ deposition are similar to those observed in sporadic, late onset AD (Davidson, Robinson, Prasher, & Mann, ; Head, Lott, Wilcock, & Lemere, ; Lemere et al, ; Liu et al, ; Mann, ; Mann & Esiri, ; Wisniewski, Bancher, Barcikowska, Wen, & Currie, ) and in addition to diffuse plaques involve cored plaques associated with dystrophic neurites (neuritic plaques), which are of neuropathological diagnostic significance in AD. Understanding structural properties, biochemical constituents, and evolution of morphologically diverse Aβ plaques and other AD‐related pathology within and between brain regions in relation to age and development of dementia is needed to guide interpretation of amyloid PET imaging of subjects with DS (Head, Helman, Powell, & Schmitt, ; Neale, Padilla, Fonseca, Holland, & Zaman, ). Compared to the extensive number of amyloid PET studies performed in AD (Cohen et al, ), there are relatively few amyloid PET studies of DS (Annus et al, , ; Cohen et al, ; Cole et al, ; Handen et al, ; Hartley et al, ; Jennings et al, ; Landt et al, ; Lao et al, , ; Mak et al, ; Matthews et al, ; Rafii et al, ; Sabbagh et al, ), even fewer longitudinal studies (Hartley et al, ; Lao et al, ; Tudorascu et al, ), and only one imaging‐to‐autopsy analysis (Sabbagh et al, ).…”

Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis

“…In most of the cases it is due to a complete trisomy of chromosome 21, while in 4%–5% of the cases the cause is a translocation or a mosaicism (2%–4%) (Coppus, ). This increased dosage of the gene products on chromosome 21 can alter diverse pathways, including those involved with brain development, metabolism, and neuronal networks (Neale, Padilla, Fonseca, Holland, & Zaman, ).…”