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Short leukocyte tel...
Short leukocyte telomeres predict 25-year Alzheimer's disease incidence in non-APOE ε4-carriers
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- Schäfer Hackenhaar, Fernanda (author)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Umeå centrum för funktionell hjärnavbildning (UFBI)
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- Josefsson, Maria, 1979- (author)
- Umeå universitet,Enheten för demografi och åldrandeforskning (CEDAR),Umeå centrum för funktionell hjärnavbildning (UFBI),Statistik
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- Nordin Adolfsson, Annelie (author)
- Umeå universitet,Psykiatri
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- Landfors, Mattias, 1977- (author)
- Umeå universitet,Patologi
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- Kauppi, Karolina (author)
- Karolinska Institutet,Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
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- Hultdin, Magnus (author)
- Umeå universitet,Patologi
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- Adolfsson, Rolf (author)
- Umeå universitet,Psykiatri
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- Degerman, Sofie, 1977- (author)
- Umeå universitet,Patologi,Institutionen för klinisk mikrobiologi
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- Pudas, Sara, Docent, 1983- (author)
- Umeå universitet,Umeå centrum för funktionell hjärnavbildning (UFBI),Institutionen för integrativ medicinsk biologi (IMB)
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(creator_code:org_t)
- 2021-07-15
- 2021
- English.
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In: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 13
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://alzres.biome...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Leukocyte telomere length
- Dementia
- Risk factors
- Time-to-event analysis
- Competing risks
- Vascular dementia
- Death
Publication and Content Type
- ref (subject category)
- art (subject category)
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