TY - JOUR
T1 - The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study
AU - Ramos-Cejudo, Jaime
AU - Johnson, Andrew D.
AU - Beiser, Alexa
AU - Seshadri, Sudha
AU - Salinas, Joel
AU - Berger, Jeffrey S.
AU - Fillmore, Nathanael R.
AU - Do, Nhan
AU - Zheng, Chunlei
AU - Kovbasyuk, Zanetta
AU - Ardekani, Babak A.
AU - Bubu, Omonigho M.
AU - Parekh, Ankit
AU - Convit, Antonio
AU - Betensky, Rebecca A.
AU - Wisniewski, Thomas M.
AU - Osorio, Ricardo S.
N1 - Publisher Copyright:
Copyright © 2021 Ramos-Cejudo, Johnson, Beiser, Seshadri, Salinas, Berger, Fillmore, Do, Zheng, Kovbasyuk, Ardekani, Bubu, Parekh, Convit, Betensky, Wisniewski and Osorio.
PY - 2021/11/30
Y1 - 2021/11/30
N2 - Objective: Active neutrophils are important contributors to Alzheimer’s disease (AD) pathology through the formation of capillary stalls that compromise cerebral blood flow (CBF) and through aberrant neutrophil signaling that advances disease progression. The neutrophil to lymphocyte ratio (NLR) is a proxy of neutrophil-mediated inflammation, and higher NLR is found in persons diagnosed with clinical AD. The objective of this study was to investigate whether increased NLR in older adults is independently associated with the risk of subsequent dementia. Methods: We examined associations of baseline NLR with incident dementia risk in the community-based Framingham Heart Study (FHS) longitudinal cohorts. The association between NLR and risk of dementia was evaluated using the cumulative incidence function (CIF) and inverse probability-weighted Cox proportional cause-specific hazards regression models, with adjustment for age, sex, body mass index (BMI), systolic and diastolic blood pressure, diabetes, current smoking status, low-density lipoprotein (LDH), high-density lipoprotein (LDL), total cholesterol, triglycerides, and history of cardiovascular disease (CVD). Random forest survival models were used to evaluate the relative predictive value of the model covariates on dementia risk. Results: The final study sample included 1,648 participants with FHS (average age, 69 years; 56% women). During follow-up (median, 5.9 years), we observed 51 cases of incident dementia, of which 41 were AD cases. Results from weighted models suggested that the NLR was independently associated with incident dementia, and it was preceded in predictive value only by age, history of CVD, and blood pressure at baseline. Conclusion: Our study shows that individuals with higher NLR are at a greater risk of subsequent dementia during a 5.9-year follow-up period. Further evaluating the role of neutrophil-mediated inflammation in AD progression may be warranted.
AB - Objective: Active neutrophils are important contributors to Alzheimer’s disease (AD) pathology through the formation of capillary stalls that compromise cerebral blood flow (CBF) and through aberrant neutrophil signaling that advances disease progression. The neutrophil to lymphocyte ratio (NLR) is a proxy of neutrophil-mediated inflammation, and higher NLR is found in persons diagnosed with clinical AD. The objective of this study was to investigate whether increased NLR in older adults is independently associated with the risk of subsequent dementia. Methods: We examined associations of baseline NLR with incident dementia risk in the community-based Framingham Heart Study (FHS) longitudinal cohorts. The association between NLR and risk of dementia was evaluated using the cumulative incidence function (CIF) and inverse probability-weighted Cox proportional cause-specific hazards regression models, with adjustment for age, sex, body mass index (BMI), systolic and diastolic blood pressure, diabetes, current smoking status, low-density lipoprotein (LDH), high-density lipoprotein (LDL), total cholesterol, triglycerides, and history of cardiovascular disease (CVD). Random forest survival models were used to evaluate the relative predictive value of the model covariates on dementia risk. Results: The final study sample included 1,648 participants with FHS (average age, 69 years; 56% women). During follow-up (median, 5.9 years), we observed 51 cases of incident dementia, of which 41 were AD cases. Results from weighted models suggested that the NLR was independently associated with incident dementia, and it was preceded in predictive value only by age, history of CVD, and blood pressure at baseline. Conclusion: Our study shows that individuals with higher NLR are at a greater risk of subsequent dementia during a 5.9-year follow-up period. Further evaluating the role of neutrophil-mediated inflammation in AD progression may be warranted.
KW - Alzheimer’s disease
KW - FHS
KW - Framingham
KW - NLR
KW - complete blood count (CBC)
KW - dementia
KW - neutrophil to lymphocyte ratio
KW - risk prediction
UR - http://www.scopus.com/inward/record.url?scp=85121374734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121374734&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2021.773984
DO - 10.3389/fnagi.2021.773984
M3 - Article
C2 - 34916927
AN - SCOPUS:85121374734
SN - 1663-4365
VL - 13
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 773984
ER -