Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers

Abstract Background Leukocyte telomere length (LTL) has been shown to predict Alzheimer’s disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E (APOE) ε4 allele carriage, the strongest genetic AD predictor. Methods We analyzed whether baseline LTL in interaction with APOE ε4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess whether the cause-specific risk of AD differed between the rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards. Results After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1–24). APOE ε4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL-APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non-APOE ε4-carriers (subdistribution hazard ratio = 3.24, CI 1.404–7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947–2.964, P = 0.07). Among APOE ε4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD. Conclusions Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non-APOE ε4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.

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Short leukocyte telomeres predict 25-year Alzheimer’s disease incidence in non-APOE ε4-carriers

10.21203/rs.3.rs-434597/v1 ◽

2021 ◽

Author(s):

Fernanda Schäfer Hackenhaar ◽

Maria Josefsson ◽

Annelie Nordin Adolfsson ◽

Mattias Landfors ◽

Karolina Kauppi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Vascular Dementia ◽

Competing Risks ◽

Hazard Ratio ◽

Competing Risk ◽

Time To Event ◽

Apoe Ε4 ◽

Specific Risk ◽

Event Models

Abstract Background: Leukocyte telomere length (LTL) has been shown to predict Alzheimer's disease (AD), albeit inconsistently. Failing to account for the competing risks between AD, other dementia types, and mortality, can be an explanation for the inconsistent findings in previous time-to-event analyses. Furthermore, previous studies indicate that the association between LTL and AD is non-linear and may differ depending on apolipoprotein E ( APOE ) ε4 allele carriage, the strongest genetic AD predictor. Methods: We analysed whether baseline LTL in interaction with APOE ε4 predicts AD, by following 1306 initially non-demented subjects for 25 years. Gender- and age-residualized LTL (rLTL) was categorized into tertiles of short, medium, and long rLTLs. Two complementary time-to-event models that account for competing risks were used; the Fine-Gray model to estimate the association between the rLTL tertiles and the cumulative incidence of AD, and the cause-specific hazard model to assess the cause-specific risk of AD between rLTL groups. Vascular dementia and death were considered competing risk events. Models were adjusted for baseline lifestyle-related risk factors, gender, age, and non-proportional hazards. Results: After follow-up, 149 were diagnosed with AD, 96 were diagnosed with vascular dementia, 465 died without dementia, and 596 remained healthy. Baseline rLTL and other covariates were assessed on average 8 years before AD onset (range 1-24). APOE ε4-carriers had significantly increased incidence of AD, as well as increased cause-specific AD risk. A significant rLTL- APOE interaction indicated that short rLTL at baseline was significantly associated with an increased incidence of AD among non- APOE ε4-carriers (subdistribution hazard ratio = 3.24, CI 1.404–7.462, P = 0.005), as well as borderline associated with increased cause-specific risk of AD (cause-specific hazard ratio = 1.67, CI 0.947–2.964, P = 0.07). Among APOE ε4-carriers, short or long rLTLs were not significantly associated with AD incidence, nor with the cause-specific risk of AD. Conclusions: Our findings from two complementary competing risk time-to-event models indicate that short rLTL may be a valuable predictor of the AD incidence in non- APOE ε4-carriers, on average 8 years before AD onset. More generally, the findings highlight the importance of accounting for competing risks, as well as the APOE status of participants in AD biomarker research.

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Dementia, Alzheimer’s Disease, and Mortality after Hemodialysis Initiation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.10150917 ◽

2018 ◽

Vol 13 (9) ◽

pp. 1339-1347 ◽

Cited By ~ 23

Author(s):

Mara A. McAdams-DeMarco ◽

Matthew Daubresse ◽

Sunjae Bae ◽

Alden L. Gross ◽

Michelle C. Carlson ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Confidence Interval ◽

Competing Risks ◽

Older Patients ◽

Disease Diagnosis ◽

Hazard Ratio ◽

Old Patients ◽

Diagnosis Of Dementia

Background and objectivesOlder patients with ESKD experience rapid declines in executive function after initiating hemodialysis; these impairments might lead to high rates of dementia and Alzheimer’s disease in this population. We estimated incidence, risk factors, and sequelae of diagnosis with dementia and Alzheimer’s disease among older patients with ESKD initiating hemodialysis.Design, setting, participants, & measurementsWe studied 356,668 older (age ≥66 years old) patients on hemodialysis (January 1, 2001 to December 31, 2013) from national registry data (US Renal Data System) linked to Medicare. We estimated the risk (cumulative incidence) of diagnosis of dementia and Alzheimer’s disease and studied factors associated with these disorders using competing risks models to account for death, change in dialysis modality, and kidney transplant. We estimated the risk of subsequent mortality using Cox proportional hazards models.ResultsThe 1- and 5-year risks of diagnosed dementia accounting for competing risks were 4.6% and 16% for women, respectively, and 3.7% and 13% for men, respectively. The corresponding Alzheimer’s disease diagnosis risks were 0.6% and 2.6% for women, respectively, and 0.4% and 2.0% for men, respectively. The strongest independent risk factors for diagnosis of dementia and Alzheimer’s disease were age ≥86 years old (dementia: hazard ratio, 2.11; 95% confidence interval, 2.04 to 2.18; Alzheimer’s disease: hazard ratio, 2.11; 95% confidence interval, 1.97 to 2.25), black race (dementia: hazard ratio, 1.70; 95% confidence interval, 1.67 to 1.73; Alzheimer’s disease: hazard ratio, 1.78; 95% confidence interval, 1.71 to 1.85), women (dementia: hazard ratio, 1.10; 95% confidence interval, 1.08 to 1.12; Alzheimer’s disease: hazard ratio, 1.12; 95% confidence interval, 1.08 to 1.16), and institutionalization (dementia: hazard ratio, 1.36; 95% confidence interval, 1.33 to 1.39; Alzheimer’s disease: hazard ratio, 1.10; 95% confidence interval, 1.05 to 1.15). Older patients on hemodialysis with a diagnosis of dementia were at 2.14-fold (95% confidence interval, 2.07 to 2.22) higher risk of subsequent mortality; those with a diagnosis of Alzheimer’s disease were at 2.01-fold (95% confidence interval, 1.89 to 2.15) higher mortality risk.ConclusionsOlder patients on hemodialysis are at substantial risk of diagnosis with dementia and Alzheimer’s disease, and carrying these diagnoses is associated with a twofold higher mortality.

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Anxiety as a risk factor of Alzheimer's disease and vascular dementia

The British Journal of Psychiatry ◽

10.1192/bjp.2018.173 ◽

2018 ◽

Vol 213 (5) ◽

pp. 654-660 ◽

Cited By ~ 33

Author(s):

Eva Becker ◽

Claudia Lorena Orellana Rios ◽

Claas Lahmann ◽

Gerta Rücker ◽

Joachim Bauer ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Vascular Dementia ◽

Functional Relation ◽

Hazard Ratio ◽

Brain Health ◽

Future Studies ◽

Prognostic Effect

BackgroundThe aetiology of dementia is not yet fully understood. Stress can have a damaging effect on brain health. The prognostic effect of anxiety is still unclear regarding Alzheimer's disease as well as vascular dementia.AimsTo explore the association between anxiety and future dementia.MethodMedline, PsycINFO, CINAHL, Web of Science and ALOIS were searched for publications up to 12 January 2018. Longitudinal studies with a follow-up of at least 2 years were included, if the trait or state anxiety had been assessed at baseline. Studies with cognitive impairment at baseline were not included. We used a random effects model to calculate the pooled time to Alzheimer's disease and incidence of vascular dementia.ResultsAnxiety predicts risk of Alzheimer's disease (n = 26 193 out of seven studies, hazard ratio1.53, 95% CI 1.16–2.01, P < 0.01) and vascular dementia (n = 4916 out of two studies, odds ratio1.88, 95% CI 1.05–3.36, P < 0.01). The pooled hazard ratio regarding risk of Alzheimer's disease was still significant when excluding studies with critical risk of bias (n = 14 110 out of six studies, hazard ratio 1.35, 95% CI 1.08–1.70, P < 0.01).ConclusionsAnxiety is a risk factor for both types of dementia. The temporal and functional relation between anxiety and dementia needs investigation in future studies. The protective value of treating anxiety should be explored further.Declaration of interestNone.

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Efficacy and tolerability of Ginkgo biloba extract EGb 761® in Alzheimer's disease and vascular dementia: Analyses of a randomised controlled trial

Zeitschrift für Phytotherapie ◽

10.1055/s-2008-1047819 ◽

2008 ◽

Vol 29 (S 1) ◽

Author(s):

R Hoerr ◽

G Sonnik ◽

O Napryeyenko

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Randomised Controlled Trial ◽

Vascular Dementia ◽

Ginkgo Biloba ◽

Controlled Trial ◽

Ginkgo Biloba Extract ◽

Egb 761 ◽

Randomised Controlled

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Can a colour blindness test help the differential diagnosis between Alzheimer's disease and vascular dementia patients?

10.26226/morressier.59d4913ad462b8029238a15e ◽

2017 ◽

Author(s):

Nikitas Arnaoutoglou

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Differential Diagnosis ◽

Vascular Dementia ◽

Dementia Patients ◽

Colour Blindness

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SPECIFIC PROPERTIES OF TUBULIN IN THE PREFRONTAL CORTEX IN CONTROL, SCHIZOPHRENIA AND VASCULAR DEMENTIA

"Medical & pharmaceutical journal "Pulse" ◽

10.26787/nydha-2686-6838-2020-22-11-65-71 ◽

2020 ◽

pp. 65-71

Author(s):

Burbaeva G.Sh. ◽

Androsova L.V. ◽

Vorobyeva E.A. ◽

Savushkina O.K.

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Prefrontal Cortex ◽

Vascular Dementia ◽

Binding Activity ◽

Nephelometric Method ◽

Rate Of Polymerization ◽

Mental Diseases ◽

And Control ◽

The Brain

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.

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