Corneal Confocal Microscopy: a potential surrogate end point for mild cognitive impairment and dementia

Transcription

1 Corneal Confocal Microscopy: a potential surrogate end point for mild cognitive impairment and dementia Navas Nadukkandiyil, Georgios Ponirakis, Hanadi Al Hamad, Adnan Khan, Marwan Ramadan, Essa AlSulaiti, Shafi Khan, Rhia Tosino, Priya Vitthal Gawhale, Maryam Alobaidi, Ahmed Elsotouhy, Noushad Thodi, Susan Osman, Marwa Elorrabi, Ioannis Petropoulos, Ahmed Own, Ashfaq Shuaib, Main Presentation Title Edit In Slide Master Anoop Sankaranarayanan, Rayaz A. Malik

2 DISCLOSURE All individuals in a position to control content (Nurse Planer, content expert, presenters, faculty, authors, and content reviewers) disclosed no relevant relationships with any commercial organization to influence the content of this activity our elders our treasure Main Presentation Title Edit In Slide Master 2

3 Background 5-8 in 100 people aged 60 have dementia Dementia is characterised by neuronal dysfunction/damage. Current diagnostic tests performed by physicians are invasive, expensive and largely based on memory. Corneal confocal microscopy (CCM), a non-invasive ophthalmic device can detect neuronal damage in peripheral (neuropathy) & central (PD, MS, ALS) neurodegenerative conditions. Question Is there a link between dementia and neurodegeneration in the cornea? Objectives Evaluate the diagnostic ability of CCM for MCI and dementia Determine the association between corneal axonal loss and cognitive and physical impairment. Design Individuals with MCI and dementia recruited from the Memory clinic and cognitively healthy controls recruited from the Geriatric clinic in Qatar between October 2016 and May 2017 Main Presentation Title Edit In Slide Master 3

4 Methods 79 patients with MCI (n=32), dementia (n=26) and age matched cognitively healthy controls (n=21) underwent clinical examination, neuropsychological testing, neuroimaging and CCM. MoCA assessment: visuospatial/executive, naming, attention, language, abstraction, delayed recall, and orientation. Normal: Corneal confocal microscopy (CCM), a noninvasive ophthalmic imaging technique, Validated for the diagnosis of neuropathy using the Heidelberg HRT III (Heidelberg Engineering GmbH, Heidelberg, Germany). Measure structural nerve loss and reinnervation in vivo. 5 images/subject within the central subbasal nerve plexus of the cornea Underwent quantification of corneal nerve fiber density (CNFD), branch density (CNBD) and length (CNFL) Main Presentation Title Edit In Slide Master 4

5 2 HbA1c, mean (SD), % 7.11 (1.30) 6.99 (1.70) 6.41 (1.15) NS NS NS Chol. mean (SD), mmol/l 4.64 (1.09) 4.40 (0.95) 4.16 (1.01) NS NS NS Trig. mean (SD), Demographic mmol/l 1.65 (0.91) and 1.82 clinical (1.38) 1.42 characteristics (0.69) NS NS NS* Hgb, mean (SD), gm/dl (1.86) (1.94) (1.59) NS NS NS MCV, mean (SD), fl (5.38) (10.60) (5.50) NS* NS NS* BP sys, mean (SD), mmhg (11.75) (15.62) (25.03) NS NS* NS* BP dias, mean (SD), mmhg (9.38) (7.76) (22.25) NS NS*.02* Controls MCI Dementia P value 1 P value 2 P value 3 Cognitive impairment (n= 21) (n= 32) (n= 26) Demographics MoCA, mean (SD) (4.99) (4.51) (5.92) <.001 <.0001 <.0001 MoCA-memory, mean (SD) (5.58) 7.78 (4.43) 6.00 (4.85) NS <.01 NS Age, mean (SD), years (7.72) (7.29) (7.77) NS NS NS MoCA-executive function, mean (SD) 4.38 (1.16) 2.28 (1.46) 1.17 (1.90) <.0001 <.0001*.02 Gender (F, M) NS NS NS MoCA-attention, mean (SD) 5.48 (0.98) 4.56 (1.76) 2.08 (1.53).05 <.0001* <.0001 Diabetes, % NS NS NS MoCA-orientation, mean (SD) 5.86 (0.48) 5.34 (1.12) 3.04 (1.37) NS <.0001* <.0001 Diabetes duration, mean (SD), years (6.13) (7.81) (8.84) NS NS NS HbA1c, Severity mean of disability (SD), % 7.11 (1.30) 6.99 (1.70) 6.41 (1.15) NS NS NS Chol. FIM, mean (SD), mmol/l (11.75) (1.09) (10.99) (0.95) (28.96) (1.01) NS <.001* NS <.01* NS Trig. mean (SD), mmol/l 1.65 (0.91) 1.82 (1.38) 1.42 (0.69) NS NS NS* Hgb, Corneal mean axonal (SD), morphology gm/dl (1.86) (1.94) (1.59) NS NS NS MCV, CNFD, mean (SD), fl No./mm (5.38) (7.98) (10.60) (9.46) (5.50) (8.15) <.01 NS* <.0001 NS NS*.03 BP CNBD, sys, mean (SD), No./mm mmhg (11.75) (48.43) (15.62) (45.92) (25.03) (39.89) <.01 NS <.0001 NS* NS*.03 BP CNFL, dias, mean mean (SD), (SD), mm/mm mmhg (9.38) (5.85) (7.76) (7.22) (22.25) (7.19) <.01 NS <.0001 NS*.02*.04 Cognitive Controls impairment vs MCI Controls vs dementia MoCA, MCI vs mean dementia (SD) (4.99) (4.51) (5.92) <.001 <.0001 <.0001 MoCA-memory, mean (SD) (5.58) 7.78 (4.43) 6.00 (4.85) NS <.01 NS MoCA-executive function, mean (SD) 4.38 (1.16) 2.28 (1.46) 1.17 (1.90) <.0001 <.0001*.02 MoCA-attention, mean (SD) 5.48 (0.98) 4.56 (1.76) 2.08 (1.53).05 <.0001* <.0001 MoCA-orientation, mean (SD) 5.86 (0.48) 5.34 (1.12) 3.04 (1.37) NS <.0001* <.0001 Severity of disability FIM, mean (SD) (11.75) (10.99) (28.96) NS <.001* <.01* Corneal axonal morphology Main Presentation Title Edit In Slide Master 5

6 Corneal confocal microscopy (CCM) Corneal sub-basal nerve plexus in: (A) (B) (C) A 70 year-old cognitively healthy control showing normal corneal axons; A 69 year old patient with mild cognitive impairment (MCI) A 69 year old patient with dementia showing a progressive reduction in corneal nerve fiber density, branch density and length. Main Presentation Title Edit In Slide Master 6

7 Fibre density Branch density Fibre length Main Presentation Title Edit In Slide Master 7

8 Age, mean (SD), years (7.72) (7.29) (7.77) NS NS NS Gender (F, M) NS NS NS Diabetes, % Demographic and clinical characteristics NS NS NS Diabetes duration, mean (SD), years (6.13) (7.81) (8.84) NS NS NS HbA1c, mean (SD), % 7.11 (1.30) 6.99 (1.70) 6.41 (1.15) NS NS NS Chol. mean (SD), mmol/l 4.64 (1.09) 4.40 (0.95) 4.16 (1.01) NS NS NS Trig. mean (SD), mmol/l 1.65 (0.91) 1.82 (1.38) 1.42 (0.69) NS NS NS* Hgb, mean (SD), gm/dl (1.86) (1.94) (1.59) NS NS NS MCV, mean (SD), fl (5.38) (10.60) (5.50) NS* NS NS* BP sys, mean (SD), mmhg Controls (11.75) MCI (15.62) Dementia (25.03) NS P value 1 NS* P value 2 NS* P value 3 BP dias, mean (SD), mmhg (n= 21) (9.38) (n= 32) (7.76) (n= 26) (22.25) NS NS*.02* Demographics Cognitive impairment Age, MoCA, mean mean (SD), (SD) years (7.72) (4.99) (7.29) (4.51) (7.77) (5.92) <.001 NS <.0001 NS <.0001 NS Gender MoCA-memory, (F, M) mean (SD) (5.58) (4.43) (4.85) 11 NS <.01 NS NS Diabetes, MoCA-executive % function, mean (SD) (1.16) (1.46) (1.90) <.0001 NS <.0001* NS.02 NS Diabetes MoCA-attention, duration, mean (SD) (SD), years (6.13) (0.98) (7.81) (1.76) (8.84) (1.53).05 NS <.0001* NS <.0001 NS HbA1c, MoCA-orientation, mean (SD), % mean (SD) (1.30) (0.48) (1.70) (1.12) (1.15) (1.37) NS <.0001* NS <.0001 NS Chol. Severity mean of disability (SD), mmol/l 4.64 (1.09) 4.40 (0.95) 4.16 (1.01) NS NS NS Trig. mean (SD), mmol/l 1.65 (0.91) 1.82 (1.38) 1.42 (0.69) NS NS NS* Hgb, FIM, mean mean (SD) (SD), gm/dl (11.75) (1.86) (10.99) (1.94) (28.96) (1.59) NS NS <.001* NS <.01* NS MCV, Corneal mean axonal (SD), morphology fl (5.38) (10.60) (5.50) NS* NS NS* BP sys, mean (SD), mmhg (11.75) (15.62) (25.03) NS NS* NS* BP CNFD, dias, mean mean (SD), (SD), No./mm mmhg (9.38) (7.98) (7.76) (9.46) (22.25) (8.15) <.01 NS <.0001 NS*.02*.03 CNBD, mean (SD), No./mm (48.43) (45.92) (39.89) <.01 < Cognitive CNFL, mean impairment (SD), mm/mm (5.85) (7.22) (7.19) <.01 < MoCA, Controls mean vs MCI (SD) (4.99) (4.51) (5.92) <.001 <.0001 <.0001 MoCA-memory, Controls vs dementia mean (SD) (5.58) 7.78 (4.43) 6.00 (4.85) NS <.01 NS MoCA-executive MCI vs dementia function, mean (SD) 4.38 (1.16) 2.28 (1.46) 1.17 (1.90) <.0001 <.0001*.02 MoCA-attention, mean (SD) 5.48 (0.98) 4.56 (1.76) 2.08 (1.53).05 <.0001* <.0001 MoCA-orientation, mean (SD) 5.86 (0.48) 5.34 (1.12) 3.04 (1.37) NS <.0001* <.0001 Severity of disability FIM, mean (SD) (11.75) (10.99) (28.96) NS <.001* <.01* Corneal axonal morphology Main Presentation Title Edit In Slide Master 8 CNFD, mean (SD), No./mm (7.98) (9.46) (8.15) <.01 <

9 Diagnostic ability of CCM Threshold value Sensitivity (%) Specificity (%) Positive likelihood ratio Negative likelihood ratio AUC 95% CI Dementia CNFD CNBD CNFL MCI CNFD CNBD CNFL Main Presentation Title Edit In Slide Master 9

10 Diagnostic ability of CCM Threshold value Sensitivity (%) Specificity (%) Positive likelihood ratio Negative likelihood ratio AUC 95% CI Dementia CNFD CNBD CNFL MCI CNFD CNBD CNFL Main Presentation Title Edit In Slide Master 10

11 Multiple linear regression analysis of corneal nerve morphology with cognitive and physical function Coefficient 95% Confidence Interval P value R-square MoCA CNFD <.01 24% CNBD < % CNFL < % MoCA-memory CNFD NS 1% CNBD NS 3% CNFL NS 2% MoCA-executive function CNFD % CNBD < % CNFL < % MoCA-attention CNFD < % CNBD <.01 19% CNFL < % MoCA-orientation CNFD <.01 28% CNBD <.01 26% CNFL <.01 28% FIM CNFD <.01 36% CNBD % CNFL <.01 32% Main Presentation Title Edit In Slide Master 11

12 Conclusions Findings: Corneal confocal microscopy (CCM) identifies nerve damage in the cornea and demonstrates good diagnostic accuracy for both mild cognitive impairment (MCI) and dementia. Corneal nerve damage relates to cognitive decline and physical disability Meaning: CCM may act as an objective, non-invasive imaging end point for neurodegeneration in patients with MCI and dementia. Main Presentation Title Edit In Slide Master 12

13 Thanks Main Presentation Title Edit In Slide Master