Progression pattern of brain mineral deposition as a differential indicator of cognitive - PowerPoint Presentation

Slide1

Progression pattern of brain mineral deposition as a differential indicator of cognitive decline

 

1 College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK. 2 Centre for Clinical Brain Sciences, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK3Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK

L. Clayson

1

, M.C. Valdés Hernández

2

,

A

.

Glatz

2

,

J.M.

Wardlaw

2

,

J.

Starr

3

Slide2

Background

Image: L

Clayson, mechanisms as reviewed in Moreno-Trevino

et al

2015

Slide3

Background

Iron

FPN

Blood vessel

Neurone

Ceruloplasmin

Glial cell

Hepcidin

bMVECs

Image: L Clayson.

Schematic representation of brain iron regulation mechanisms (as detailed in McCarthy &

Kosman

2014).

[

FPN:

Ferroportin

,

bMVECS

: brain microvascular endothelial cells].

Brain glial cell regulation of

iron

Slide4

BackgroundImage: L

Clayson. Schematic representation of mineral deposition mechanisms

Slide5

1. There is a distinctive pattern of mineral deposition depending on the cognitive status (CN, MCI or AD) of patients

2. With

cognitive decline, mineral deposition increases in regions know to be associated with increased amyloid depositionHypotheses

Slide6

To investigate the prevalence of basal ganglia mineral deposition (BGMD) and brain microbleeds in individuals of cognitive status ranging from CN to AD

To improve our imaging techniques by developing a specific cognitively-relevant atlas of the distribution of mineral deposits with estimates of the main mineral content per region.

Aims

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Is there a progression pattern of brain mineral deposition that can be used as a differential indicator of cognitive

decline?

Ultimately..

Slide8

Methods

ADNI DatabaseSelection Criteria:

Sample 1: M.R.I. FLAIR, T2* & MPRAGE for 3 yearsSample 2: MRI data for 1 year

Slide9

Semi-Automatic Software: -

Analyze 11.0, MRIcronBGMD Measurements

- Automatic Pipeline (Glatz et al, 2015)Microbleed Visual Assessments

Methods (2)

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Methods (3)

 

Patient Cognitive Status  Assessment

 

CN

 

EMCI

 

LMCI

 

AD

 

MMSE Score

 

24-30

 

24-30

 

24-30 

20-26 CDR (Clinical Dementia Rating)

 0.0 

0.5 0.5

 0.5/1.0

 Wechsler Memory Scale Logical Memory II

 ≥16 years: ≥9

8-15 years: ≥50-7 years: ≥3 

≥ 16 years: 9-118-15 years: 5-90-7 years: 3-6

 ≥16 years: ≤ 88-15 years: ≤4

0-7 years: ≤2 

≥16 years: ≤ 88-15 years: ≤40-7 years: ≤2

Following blinded assessments, cognitive status was recorded

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Results – Longitudinal Analysis

Sample 1 microbleeds:

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Microbleed Progression by Cognitive Status

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Probability Atlas of microbleed distribution by cognitive group

Red indicates areas prominently affectedSAMPLE 1:Image analysis of microbleeds

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Results Total B.G. Mineral deposition

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BGMD Progression by Cognitive Status

+ Predominant Iron and Calcium

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Cognitively Relevant atlas of mineral deposition

SAMPLE 1:

Image analysis of total BGMD

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ResultsCross Sectional Study

Sample 2: Microbleed Prevalence

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Sample 2: Total BGMD followed the same pattern as the sample 1

Results – Cross Sectional Study

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SAMPLE 2:

Image analysis of total BGMD

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Lack of association between microbleeds and cognitive decline in AD (van der Vlies et al,

2012) Microbleeds increase in AD (Yates et al 2014)Insignificant BGMD results (

Valdés Hernández et al 2012)Similar pattern in serum and CSF (Lavados et al 2008, Mueller et al 2012)Validation method showed ageing > TG alteration (Park et al, 2014)Power, Protocols, Risk Factors, Cognitive Decline

Discussion

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Increased mineralisation and microbleed load amongst patients from CN to LMCI and gradual decrease towards AD could be of potential use as a differential indicator in the diagnosis of AD

Conclusions

CN

EMCI

LMCI

AD

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Microbleeds and BGMD may be useful indicators of mild cognitive impairment. Need to replicate this study in a larger sample + follow progression over a longer time period.

Do microbleeds/BGMD disappear when LMCI patients progress to AD/ if so why?Conclusions

Slide23

Glatz A, Bastin ME, Kiker AJ, Deary IJ,

Wardlaw JM, & Hernández MCV (2015). Automated segmentation of multifocal basal ganglia T2*-weighted MRI hypointensities. NeuroImage 105,

332-346.Lavados M, Guillón M, Mujica MC, Rojo LE, Fuentes P, Maccioni RB (2008). Mild cognitive impairment and Alzheimer patients display different levels of redox-active CSF iron. J Alzheimers Dis 13(2), 225-32.Mueller C,

Schrag

M, Crofton A,

Stolte

J,

Muckenthaler

MU,

Magaki

S, Kirsch W (2012). Altered serum iron and copper homeostasis predicts cognitive decline in mild cognitive impairment.

J

Alzheimers

Dis 29(2), 341-50. Park L, Koizumi K, El Jamal S, Zhou P, Previti ML, Van Nostrand WE, Carlson G, Iadecola C (2014). Age-dependent neurovascular dysfunction and damage in a mouse model of cerebral amyloid

angiopathy. Stroke 45(6),1815-21.Valdés Hernández Mdel C, Maconick LC, Tan EM & Wardlaw

JM (2012). Identification of mineral deposits in the brain on radiological images: a systematic review. Eur Radiol 22(11), 2371-81.van der Vlies AE, Goos

JD, Barkhof F, Scheltens P, van der Flier WM (2012). Microbleeds do not affect rate of cognitive decline in Alzheimer disease. Neurology 79

, 763–769Yates PA, Desmond PM, Phal PM, Steward C, Szoeke C, Salvado O, Ellis KA, Martins RN, Masters CL, Ames D, Villemagne VL, Rowe CC & AIBL Research Group (2014). Incidence of cerebral microbleeds in preclinical Alzheimer disease. Neurology

82(14), 1266-73References

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Validation

Images: L Clayson, MV

Hernández