point for mild cognitive impairment and dementia Navas Nadukkandiyil - PowerPoint PPT Presentation

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

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 2 Main Presentation Title Edit In Slide Master

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 3 Main Presentation Title Edit In Slide Master

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: ≥ 26-30 . Corneal confocal microscopy (CCM) , a non- invasive 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 ) 4 Main Presentation Title Edit In Slide Master

Demographic and clinical characteristics Controls MCI Dementia P value 1 P value 2 P value 3 (n= 21) (n= 32) (n= 26) Demographics Age, mean (SD), years 68.57 (7.72) 69.47 (7.29) 72.96 (7.77) NS NS NS Gender (F, M) 13 8 16 16 15 11 NS NS NS Diabetes, % 71.43 59.38 48.00 NS NS NS Diabetes duration, mean (SD), years 11.53 (6.13) 13.47 (7.81) 14.42 (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 13.69 (1.86) 12.68 (1.94) 12.98 (1.59) NS NS NS MCV, mean (SD), fL 84.71 (5.38) 83.69 (10.60) 86.74 (5.50) NS* NS NS* BP sys, mean (SD), mmHg 144.76 (11.75) 141.78 (15.62) 145.67 (25.03) NS NS* NS* BP dias, mean (SD), mmHg 76.10 (9.38) 74.88 (7.76) 66.35 (22.25) NS NS* .02* CNFL, mean (SD), mm/mm 25.67 (5.85) 19.61 (7.22) 15.65 (7.19) <.01 <.0001 .04 1 Controls vs MCI 2 Controls vs dementia 3 MCI vs dementia 5 Main Presentation Title Edit In Slide Master

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

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

Demographic and clinical characteristics Controls MCI Dementia P value 1 P value 2 P value 3 (n= 21) (n= 32) (n= 26) Cognitive impairment MoCA, mean (SD) 26.19 (4.99) 21.03 (4.51) 13.71 (5.92) <.001 <.0001 <.0001 MoCA-memory, mean (SD) 10.29 (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) 120.08 (11.75) 116.71 (10.99) 94.27 (28.96) NS <.001* <.01* Corneal axonal morphology CNFD, mean (SD), No./mm 2 32.59 (7.98) 24.61 (9.46) 19.34 (8.15) <.01 <.0001 .03 CNBD, mean (SD), No./mm 2 114.87 (48.43) 78.91 (45.92) 53.92 (39.89) <.01 <.0001 .03 CNFL, mean (SD), mm/mm 2 25.67 (5.85) 19.61 (7.22) 15.65 (7.19) <.01 <.0001 .04 1 Controls vs MCI 2 Controls vs dementia 3 MCI vs dementia 8 Main Presentation Title Edit In Slide Master

Diagnostic ability of CCM Positive Negative Threshold Sensitivity Specificity likelihood likelihood AUC 95% CI value (%) (%) ratio ratio Dementia CNFD 0.86 0.75 – 0.96 28 84.62 71.43 0.79 0.79 CNBD 0.85 0.70 – 0.95 64 73.08 90.48 0.90 0.73 CNFL 0.85 0.70 – 0.95 21 80.77 80.95 0.84 0.77 MCI CNFD 0.73 0.64 – 0.89 28 65.63 71.43 0.78 0.58 CNBD 0.72 0.61 – 0.88 100 81.25 57.14 0.74 0.67 CNFL 0.75 0.66 – 0.90 22 71.88 71.43 0.79 0.63 9 Main Presentation Title Edit In Slide Master

Diagnostic ability of CCM Positive Negative Threshold Sensitivity Specificity likelihood likelihood AUC 95% CI value (%) (%) ratio ratio Dementia CNFD 0.86 0.75 – 0.96 28 84.62 71.43 0.79 0.79 CNBD 0.85 0.70 – 0.95 64 73.08 90.48 0.90 0.73 CNFL 0.85 0.70 – 0.95 21 80.77 80.95 0.84 0.77 MCI CNFD 0.73 0.64 – 0.89 28 65.63 71.43 0.78 0.58 CNBD 0.72 0.61 – 0.88 100 81.25 57.14 0.74 0.67 CNFL 0.75 0.66 – 0.90 22 71.88 71.43 0.79 0.63 10 Main Presentation Title Edit In Slide Master

Multiple linear regression analysis of corneal nerve morphology with cognitive and physical function Coefficient 95% Confidence Interval P value R-square MoCA CNFD 0.26 0.10 - 0.42 <.01 24% CNBD 0.05 0.03 - 0.08 <.001 27% CNFL 0.37 0.18 - 0.57 <.001 28% MoCA-memory CNFD 0.03 -0.10 - 0.17 NS 1% CNBD 0.02 -0.01 - 0.04 NS 3% CNFL 0.07 -0.09 - 0.24 NS 2% MoCA-executive function CNFD 0.08 0.04 - 0.12 .0001 36% CNBD 0.02 0.01 - 0.02 <.0001 38% CNFL 0.12 0.07 - 0.17 <.0001 41% MoCA-attention CNFD 0.09 0.04 - 0.13 <.001 22% CNBD 0.01 0.01 - 0.02 <.01 19% CNFL 0.11 0.05 - 0.17 <.001 22% MoCA-orientation CNFD 0.05 0.02 - 0.09 <.01 28% CNBD 0.01 0.01 - 0.02 <.01 26% CNFL 0.07 0.03 - 0.11 <.01 28% FIM CNFD 0.89 0.34 - 1.45 <.01 36% CNBD 0.11 0.01 - 0.22 .03 29% CNFL 0.95 0.25 - 1.65 <.01 32% 11 Main Presentation Title Edit In Slide Master

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. 12 Main Presentation Title Edit In Slide Master

Thanks Main Presentation Title Edit In Slide Master