The Predictability of Eye Disease for Alzheimer Disease
The Predictability of Eye Disease for Alzheimer Disease 由眼睛疾病預測阿茲海默症 臺北市立聯合醫院 翁林仲 陳少鈞
Alzheimer's disease (AD) Age associated >65 y/o: 6. 7% Dementia(老年癡呆) Senile plaque (老年斑) Neurofibrillary tangle (神經纖維)
� � Data sources: 2000 -2011 Relative hazards ratio of Alzheimer‘s disease in the diabetic(糖尿病) and control groups 4
Relative hazards of AD in relation to diabetes and various covariates � Diabetes, female, >65 y/o, low insurance premium, north and south geographic area
hazards of AD(腦血管) in relationdisease, cardiovascular to diabetes and various covariates Cerebrovascular (心血管) disease, hypertension(高血壓) � Relative
W W h y Alzheimer’s disease r e l a t e t o o c u l a r p r o b l e m
Retina (視網膜) The integral part of CNS
RPE 視網膜色素層 Ohno-Matsui K. Prog Retin Eye Res. 2011
E Evidence of Alzheimer’s disease in eye problem
� Relative hazards ratio of Alzheimer's disease in the diabetic and control groups (2012) � Adjusted odds ratio of Alzheimer‘s disease in the diabetic retinopathy(糖尿病視網膜病變), glaucoma( 青光眼), age-related macular disease (老年性黃斑部病變)and control groups (2013)
Diabetic Retinopathy(糖尿病視網膜病變)
Odds Ratio of AD (DMR: 362. 01 362. 02 250. 50 250. 51 250. 52 250. 53) Variable Number of Events of Patients(%) (prevalence) Adjusted OR(AOR) 95% CI P value Age <65 y/o 2850(49. 2%) 2(0. 070%) 1. 00 ≥ 65 y/o 2946(50. 8%) 6(0. 204%) 3. 015 0. 605 -15. 022 0. 1779 Sex Male 3066(52. 9%) 0 1. 00 Female 2730(47. 1%) 8(0. 293%) >999. 999 <0. 001 - >999. 999 0. 9372 3. 059 -75. 620 0. 0009* Diabetic retinopathy No 4830(83. 3%) 2(0. 041%) 1. 00 Yes 966(16. 67%) 6(0. 621%) 15. 208 Total 5796 8(0. 138%) Woung LC, Chen SC. 2013 14
Age-related Macular Degeneration (老年性黃斑部病變) 15
Age-related Macular Degeneration and Alzheimer’s Disease Rotterdam Study, prospective population-based study, aged 75 years or older (n = 1, 438), advanced age-related maculopathy increased risk of Alzheimer's disease. Am J Epidemiol. Is age-related maculopathy associated with Alzheimer's Disease? The Rotterdam Study. 1999 16
Odds Ratio of AD (AMD: 362. 50 362. 51 362. 52) Variable Number of Patients(%) Number of Events (prevalence ) Adjusted OR(AOR) 95% CI P value Age <65 y/o 516(20. 5%) 1(0. 194%) 1. 00 ≥ 65 y/o 1988(79. 5%) 8(0. 402%) 2. 236 Male 1530(60. 9%) 4(0. 261%) 1. 00 984(39. 1%) 5(0. 508%) 2. 049 2095(83. 3%) 1(0. 048%) 1. 00 419(16. 7%) 8(1. 909%) 40. 908 0. 275 -18. 166 0. 4516 0. 542 -7. 746 0. 2904 5. 100 -328. 127 0. 0005* Sex Female Age-related macular disease No Yes Total 2514 9(0. 358%) Woung LC, Chen SC. 2013 17
Glaucoma(青光眼)
Odds Ratio of AD (Glaucoma : 365. *) Variable Number of Patients(%) Number of Events (prevalence ) Adjusted OR(AOR) 95% CI P value Age <65 y/o 5630(34. 6%) 5(0. 089%) 1. 00 ≥ 65 y/o 10632(65. 4%) 38(0. 357%) 4. 328 Male 7466(45. 9%) 15(0. 201%) 1. 00 Female 8796(54. 1%) 28(0. 318%) 1. 773 13550(83. 3%) 7(0. 052%) 1. 00 2712(16. 7%) 36(1. 327%) 26. 154 1. 696 -11. 047 0. 0022* 0. 942 -3. 337 0. 0761 11. 623 -58. 852 <. 0001** Sex Glaucoma No Yes Total 16262 43(0. 264%) Woung LC, Chen SC. 2013 19
AD Glaucoma AMD Location RGC, NFL, ONH RPE, phtotreceptor Amyloid deposition Senile plaque RGC Drusen p. Tau NGT Inner retina, vitreous, ONH No Oxidative & metabolic stress Metal Metabolic deficiency strain Neural damage Around senile Glial reactivity plaque Genetic linkage APOE In NFL, ONH Visual cycle Drusen Around drusen APOE Jeremy M. Sivak. IOVS 2013
Retinal Vessels Calibers(網膜血管口徑) and Dementia � � Population-based Rotterdam Study: 1065 persons (mean age, 67. 5 y and 51% women) Narrower retinal arteriolar and wider retinal venular calibers associated with smaller brain volume primarily white matter. Alzheimer Dis Assoc Disord, Retinal Vascular Calibers Associate Differentially With Cerebral Gray Matter and White Matter Atrophy. 2013 Ikram MK, Alzheimer Dis Assoc Disord. 2013
Ocular (Optical) Coherence Tomography(斷層掃描) Retinal nerve fiber layer
RNFL thickness -49. 5 μm 0 24 He XF. Int JHe Ophthalmol. 2012 XF. Int J Ophthalmol. 2012
Flash-Visual Evoked Potentials(閃光視覺誘發電位) under open- or close- eyes changed in Alzheimer‘s disease Tartaglione A, BMC Neurol. 2012
F-VEP: P 2 latency (mean ± SE) Eye-open (EO) Eye-closed (EC) EC – EO Control AD 136. 7 ± 3. 6 140. 4 ± 3. 1 132. 5 ± 3. 1 145. 7 ± 3. 9 3. 7 ± 2. 6 13. 2 ± 2. 2 Tartaglione A. BMC Neurol. 2012 F-VEP can be viewed as a reliable marker of AD
Eye-hand coordination
Eye-hand Coordination Impaired in Early. Alzheimer’s Disease (damage to the parietal lobe) ßEyeball movement AD Normal ßHand movement AD Normal J Alzheimers Dis. Visuomotor impairment in early-stage Alzheimer's disease: changes in relative timing of eyeand hand movements. 2012
Conclusions � � This national population-based cohort study provides support for the putative link between diabetes (retinopathy), glaucoma, AMD, and AD A link is particularly evident in female and in older diabetes. We suggest a need for routine mental and cognitive examinations in diabetic patients in order for early for detection(檢測) and therapeutic treatments of ad. Female and older diabetic patients and their family should be particularly informed of such increased risk, and avoidance of other risk factors for ad should be exercised accordingly.
Additional Conclusions � � � Several degeneration diseases of optic nerve( 視神經) or retina are associated with AD. Various ophthalmological or neuroophthalmological examinations could detect or predict AD. Ophthalmologists will take important part in AD diagnosis and monitoring.
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