Comorbidity of age-related macular degeneration with Alzheimer’s disease: A histopathologic case-control study

Smilnak, Gordon; Deans, John; Doraiswamy, P. Murali; Stinnett, Sandra S.; Whitson, Heather E.; Lad, Eleonora M.

doi:10.1371/journal.pone.0223199

Cited by 8 publications

(15 citation statements)

References 49 publications

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“…A previous study in CHS found that the ε2 allele was associated with a 2.5 times greater odds of late age‐related maculopathy, whereas the ε4 allele may confer some protection 29 . Other studies suggest that despite the biochemical and histological similarities between AMD and AD, these diseases have separate genetic risk profiles and distinct pathophysiology 30,31 . A meta‐analysis found a significant association between AMD and dementia, including AD 32 .…”

Section: Discussionmentioning

confidence: 99%

“…29 Other studies suggest that despite the biochemical and histological similarities between AMD and AD, these diseases have separate genetic risk profiles and distinct pathophysiology. 30,31 A meta-analysis found a significant association between AMD and dementia, including AD. 32 Furthermore, other epidemiologic studies suggest that the dry form of AMD is more strongly related to cognitive impairment than the wet form of AMD.…”

Section: F I G U R Ementioning

confidence: 99%

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Ophthalmic conditions associated with dementia risk: The Cardiovascular Health Study

Hwang

Longstreth

Thielke

et al. 2021

Alzheimer's & Dementia

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Introduction Ophthalmic conditions and dementia appear to overlap and may share common pathways, but research has not differentiated dementia subtypes. Methods Diagnoses of cataracts, age‐related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma were based on medical histories and International Classification of Diseases, Ninth Revision (ICD‐9) codes for 3375 participants from the Cardiovascular Health Study. Dementia, including Alzheimer's disease (AD) and vascular dementia (VaD), was classified using standardized research criteria. Results Cataracts were associated with AD (hazard ratio [HR] = 1.34; 95% confidence interval [CI] = 1.01‐1.80) and VaD/mixed dementia (HR = 1.41; 95% CI = 1.02‐1.95). AMD was associated with AD only (HR = 1.87; 95% CI = 1.13‐3.09), whereas DR was associated with VaD/mixed dementia only (HR = 2.63; 95% CI = 1.10‐6.27). Discussion Differential associations between specific ophthalmic conditions and dementia subtypes may elucidate pathophysiologic pathways. Lack of association between glaucoma and dementia was most surprising from these analyses.

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Section: Discussionmentioning

confidence: 99%

Section: F I G U R Ementioning

confidence: 99%

Ophthalmic conditions associated with dementia risk: The Cardiovascular Health Study

Hwang

Longstreth

Thielke

et al. 2021

Alzheimer's & Dementia

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“…Only one qualitative study and one quantitative study provided data on the impact of comorbid VI on caregivers. Most studies were from the United States of America (USA) (nine studies) [ 13 , 19 , 23 , 25 , 28 , 35 , 38 , 41 , 43 ] and the United Kingdom (UK) (ten studies) [ 12 , 16 , 17 , 22 , 26 , 27 , 37 , 44 , 47 ]. Three studies were from China [ 21 , 31 , 33 ] and one global study [ 40 ] reported data from low- and middle-income countries (Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Prevalence of visual impairment in older people living with dementia and its impact: a scoping review

et al. 2023

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Background and objectives Visual impairment (VI) and dementia both increase with age, and it is likely that many older people are living with both conditions. This scoping review aims to investigate the prevalence and types of VI among older people living with dementia, and the impact of VI on older people living with dementia and their caregivers. Methods This scoping review used Arksey and O’Malley’s methodological framework. Studies in any setting involving people living with dementia and some assessment of either VI, eye diseases causing VI or the impact of VI were included. Results Thirty-six studies were included. Thirty-one studies reported the prevalence of VI in older people living with dementia, while ten studies reported on impacts of VI on people living with dementia. Only one study reported on impacts on caregivers. The prevalence of VI or specific eye diseases among older people living with dementia ranged from 0.2 to 74%. The impacts of VI on older people living with dementia included increased use of hospital services, increased disability and dependency, reduced social engagement, negative emotions, increased abnormal behaviours, loss of hobbies, difficulty in using visual aids or memory aids, and greater Neuropsychiatric Inventory symptoms. And the impacts on caregivers included increased conflict and physical exhaustion. Conclusion VI is common in older people living with dementia and is associated with negative impacts on those with dementia and their caregivers. However, heterogeneity between studies in terms of setting and method for assessing and defining VI make it difficult to compare findings among studies. Further research is needed, particularly assessing the impact on caregivers.

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“…NGFR, also known as p75NTR, is a receptor of neurotrophin which regulates various cell functions and is implicated in Alzheimer's disease [42][43][44]. A link between Alzheimer's disease and AMD has been previously reported [45][46][47]. This indicates that SMAD2 and NGFR are implicated in AMD.…”

Section: Smad2 and Ngfr Were Identified As Hub Gens Through Functional Epigenetic Module Analysismentioning

confidence: 97%

Integrated Analysis of DNA methylation and transcriptome profile to identify key features of age-related macular degeneration

et al. 2021

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Age-related macular degeneration (AMD) is a common vision-threatening disease. The current study sought to integrate DNA methylation with transcriptome profile to explore key features in AMD. Gene expression data were obtained from the Gene Expression Omnibus (GEO, accession ID: GSE135092) and DNA methylation data were obtained from the ArrayExpress repository (E-MTAB-7183). A total of 456 differentially expressed genes (DEGs) and 4827 intragenic differentially methylated CpGs (DMCs) were identified between AMD and controls. DEGs and DMCs were intersected and 19 epigenetically induced (EI) genes and 15 epigenetically suppressed (ES) genes were identified. Immune cell infiltration analysis was performed to estimate the abundance of different types of immune cell in each sample. Enrichment scores of inflammatory response and tumor necrosis factor-alpha (TNFα) signaling via nuclear factor kappa B (NF-κb) were positively correlated with abundance of activated memory CD4 T cells and M1 macrophages. Subsequently, two significant random forest classifiers were constructed based on DNA methylation and transcriptome data. SMAD2 and NGFR were selected as key genes through functional epigenetic modules (FEM) analysis. Expression level of SMAD2, NGFR and their integrating proteins was validated in hydrogen peroxide (H 2 O 2 ) and TNFα co-treated retinal pigment epithelium (RPE) in vitro. The findings of the current study showed that local inflammation and systemic inflammatory host response play key roles in pathogenesis of AMD. SMAD2 and NGFR provide new insight in understanding the molecular mechanism and are potential therapeutic targets for development of AMD therapy.

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Comorbidity of age-related macular degeneration with Alzheimer’s disease: A histopathologic case-control study

Cited by 8 publications

References 49 publications

Ophthalmic conditions associated with dementia risk: The Cardiovascular Health Study

Ophthalmic conditions associated with dementia risk: The Cardiovascular Health Study

Prevalence of visual impairment in older people living with dementia and its impact: a scoping review

Integrated Analysis of DNA methylation and transcriptome profile to identify key features of age-related macular degeneration

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