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Elijah Mak

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4 papers
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4

YNIMG Journal 2021 Journal Article

Proximity to dementia onset and multi-modal neuroimaging changes: The prevent-dementia study

  • Elijah Mak
  • Maria-Eleni Dounavi
  • Audrey Low
  • Stephen F. Carter
  • Elizabeth McKiernan
  • Guy B Williams
  • P Simon Jones
  • Isabelle Carriere

BACKGROUND: First-degree relatives of people with dementia (FH+) are at increased risk of developing Alzheimer's disease (AD). Here, we investigate "estimated years to onset of dementia" (EYO) as a surrogate marker of preclinical disease progression and assess its associations with multi-modal neuroimaging biomarkers. METHODS: ) was performed on voxelwise statistical maps. RESULTS: p < 0.05). The influence of EYO on white matter deficits were significantly stronger compared to that of normal ageing. APOE-ε4 carriers exhibited hyperperfusion with nearer proximity to estimated onset in temporo-parietal regions. There were no interactions between EYO and time, suggesting that EYO was not associated with accelerated imaging changes in this sample. CONCLUSIONS: Amongst cognitively normal midlife adults with a family history of dementia, a shorter hypothetical proximity to dementia onset may be associated with incipient brain abnormalities, characterised by white matter disruptions and perfusion abnormalities, particularly amongst APOE-ε4 carriers. Our findings also confer biological validity to the construct of EYO as a potential stage marker of preclinical progression in the context of sporadic dementia. Further clinical follow-up of our longitudinal sample would provide critical validation of these findings.

YNICL Journal 2020 Journal Article

Correlation of microglial activation with white matter changes in dementia with Lewy bodies

  • Nicolas Nicastro
  • Elijah Mak
  • Guy B. Williams
  • Ajenthan Surendranathan
  • W Richard Bevan-Jones
  • Luca Passamonti
  • Patricia Vàzquez Rodrìguez
  • Li Su

C]-PK11195 binding in frontal, temporal, and occipital lobes. However, microglial activation was not significantly associated with grey matter changes. Our study suggests that increased microglial activation is associated with a relative preservation of white matter and cognition in DLB, positioning neuroinflammation as a potential early marker of DLB etio-pathogenesis.

YNICL Journal 2017 Journal Article

Associations of hippocampal subfields in the progression of cognitive decline related to Parkinson's disease

  • Heidi Foo
  • Elijah Mak
  • Russell Jude Chander
  • Aloysius Ng
  • Wing Lok Au
  • Yih Yian Sitoh
  • Louis C.S. Tan
  • Nagaendran Kandiah

OBJECTIVE: Hippocampal atrophy has been associated with mild cognitive impairment (MCI) in Parkinson's disease (PD). However, literature on how hippocampal atrophy affects the pathophysiology of cognitive impairment in PD has been limited. Previous studies assessed the hippocampus as an entire entity instead of their individual subregions. We studied the progression of cognitive status in PD subjects over 18 in relation to hippocampal subfields atrophy. METHODS: 65 PD subjects were included. Using the MDS task force criteria, PD subjects were classified as either having no cognitive impairment (PD-NCI) or PD-MCI. We extended the study by investigating the hippocampal subfields atrophy patterns in those who converted from PD-NCI to PD-MCI (PD-converters) compared to those who remained cognitively stable (PD-stable) over 18 months. Freesurfer 6.0 was used to perform the automated segmentation of the hippocampus into thirteen subregions. RESULTS: PD-MCI showed lower baseline volumes in the left fimbria, right CA1, and right HATA; and lower global cognition scores compared to PD-NCI. Baseline right CA1 was also correlated with baseline attention. Over 18 months, decline in volumes of CA2-3 and episodic memory were also seen in PD-converters compared to PD-stable. Baseline volumes of GC-DG, right CA4, left parasubiculum, and left HATA were predictive of the conversion from PD-NCI to PD-MCI. CONCLUSION: The findings from this study add to the anatomical knowledge of hippocampal subregions in PD, allowing us to understand the unique functional contribution of each subfield. Structural changes in the hippocampus subfields could be early biomarkers to detect cognitive impairment in PD.

YNICL Journal 2015 Journal Article

Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies

  • Elijah Mak
  • Li Su
  • Guy B. Williams
  • Rosie Watson
  • Michael Firbank
  • Andrew M. Blamire
  • John T. O'Brien

Background & objective Percent whole brain volume change (PBVC) measured from serial MRI scans is widely accepted as a sensitive marker of disease progression in Alzheimer's disease (AD). However, the utility of PBVC in the differential diagnosis of dementia remains to be established. We compared PBVC in AD and dementia with Lewy bodies (DLB), and investigated associations with clinical measures. Methods 72 participants (14 DLBs, 25 ADs, and 33 healthy controls (HCs)) underwent clinical assessment and 3 Tesla T1-weighted MRI at baseline and repeated at 12 months. We used FSL-SIENA to estimate PBVC for each subject. Voxelwise analyses and ANCOVA compared PBVC between DLB and AD, while correlational tests examined associations of PBVC with clinical measures. Results AD had significantly greater atrophy over 1 year (1. 8%) compared to DLB (1. 0%; p = 0. 01) and HC (0. 9%; p < 0. 01) in widespread regions of the brain including periventricular areas. PBVC was not significantly different between DLB and HC (p = 0. 95). There were no differences in cognitive decline between DLB and AD. In the combined dementia group (AD and DLB), younger age was associated with higher atrophy rates (r = 0. 49, p < 0. 01). Conclusions AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.