Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia: A population-based study

Anna Pink, Gorazd B. Stokin, Mairead M. Bartley, Rosebud O Roberts, Ondrej Sochor, Mary Margaret Machulda, Janina Krell-Roesch, David S Knopman, Jazmin I. Acosta, Teresa J. Christianson, V. Shane Pankratz, Michelle M Mielke, Ronald Carl Petersen, Yonas Endale Geda

Research output: Contribution to journalArticle

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Abstract

Objective: To investigate the population-based interaction between a biological variable (APOE ε4), neuropsychiatric symptoms, and the risk of incident dementia among subjects with prevalent mild cognitive impairment (MCI). Methods: We prospectively followed 332 participants with prevalent MCI (aged 70 years and older) enrolled in the Mayo Clinic Study of Aging for a median of 3 years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria, after reviewing neurologic, cognitive, and other pertinent data. Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Questionnaire. We used Cox proportional hazards models, with age as a time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were adjusted for sex, education, and medical comorbidity. Results: Baseline agitation, nighttime behaviors, depression, and apathy significantly increased the risk of incident dementia. We observed additive interactions between APOE ε4 and depression (joint effect HR = 2.21; 95%CI = 1.24-3.91; test for additive interaction, p < 0.001); and between APOE ε4 and apathy (joint effect HR = 1.93; 95% CI = 0.93-3.98; test for additive interaction, p = 0.031). Anxiety, irritability, and appetite/eating were not associated with increased risk of incident dementia. Conclusions: Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression, and apathy elevated the risk of incident dementia. There was a synergistic interaction between depression or apathy and APOE ε4 in further elevating the risk of incident dementia.

Original languageEnglish (US)
Pages (from-to)935-943
Number of pages9
JournalNeurology
Volume84
Issue number9
DOIs
StatePublished - Mar 3 2015

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Dementia
Apathy
Depression
Population
Confidence Intervals
Sex Education
Appetite
Proportional Hazards Models
Nervous System
Comorbidity
Consensus
Anxiety
Eating
Equipment and Supplies
Cognitive Dysfunction

ASJC Scopus subject areas

  • Clinical Neurology

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Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia : A population-based study. / Pink, Anna; Stokin, Gorazd B.; Bartley, Mairead M.; Roberts, Rosebud O; Sochor, Ondrej; Machulda, Mary Margaret; Krell-Roesch, Janina; Knopman, David S; Acosta, Jazmin I.; Christianson, Teresa J.; Pankratz, V. Shane; Mielke, Michelle M; Petersen, Ronald Carl; Geda, Yonas Endale.

In: Neurology, Vol. 84, No. 9, 03.03.2015, p. 935-943.

Research output: Contribution to journalArticle

Pink, A, Stokin, GB, Bartley, MM, Roberts, RO, Sochor, O, Machulda, MM, Krell-Roesch, J, Knopman, DS, Acosta, JI, Christianson, TJ, Pankratz, VS, Mielke, MM, Petersen, RC & Geda, YE 2015, 'Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia: A population-based study', Neurology, vol. 84, no. 9, pp. 935-943. https://doi.org/10.1212/WNL.0000000000001307
Pink, Anna ; Stokin, Gorazd B. ; Bartley, Mairead M. ; Roberts, Rosebud O ; Sochor, Ondrej ; Machulda, Mary Margaret ; Krell-Roesch, Janina ; Knopman, David S ; Acosta, Jazmin I. ; Christianson, Teresa J. ; Pankratz, V. Shane ; Mielke, Michelle M ; Petersen, Ronald Carl ; Geda, Yonas Endale. / Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia : A population-based study. In: Neurology. 2015 ; Vol. 84, No. 9. pp. 935-943.
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abstract = "Objective: To investigate the population-based interaction between a biological variable (APOE ε4), neuropsychiatric symptoms, and the risk of incident dementia among subjects with prevalent mild cognitive impairment (MCI). Methods: We prospectively followed 332 participants with prevalent MCI (aged 70 years and older) enrolled in the Mayo Clinic Study of Aging for a median of 3 years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria, after reviewing neurologic, cognitive, and other pertinent data. Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Questionnaire. We used Cox proportional hazards models, with age as a time scale, to calculate hazard ratios (HRs) and 95{\%} confidence intervals (CIs). Models were adjusted for sex, education, and medical comorbidity. Results: Baseline agitation, nighttime behaviors, depression, and apathy significantly increased the risk of incident dementia. We observed additive interactions between APOE ε4 and depression (joint effect HR = 2.21; 95{\%}CI = 1.24-3.91; test for additive interaction, p < 0.001); and between APOE ε4 and apathy (joint effect HR = 1.93; 95{\%} CI = 0.93-3.98; test for additive interaction, p = 0.031). Anxiety, irritability, and appetite/eating were not associated with increased risk of incident dementia. Conclusions: Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression, and apathy elevated the risk of incident dementia. There was a synergistic interaction between depression or apathy and APOE ε4 in further elevating the risk of incident dementia.",
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T1 - Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia

T2 - A population-based study

AU - Pink, Anna

AU - Stokin, Gorazd B.

AU - Bartley, Mairead M.

AU - Roberts, Rosebud O

AU - Sochor, Ondrej

AU - Machulda, Mary Margaret

AU - Krell-Roesch, Janina

AU - Knopman, David S

AU - Acosta, Jazmin I.

AU - Christianson, Teresa J.

AU - Pankratz, V. Shane

AU - Mielke, Michelle M

AU - Petersen, Ronald Carl

AU - Geda, Yonas Endale

PY - 2015/3/3

Y1 - 2015/3/3

N2 - Objective: To investigate the population-based interaction between a biological variable (APOE ε4), neuropsychiatric symptoms, and the risk of incident dementia among subjects with prevalent mild cognitive impairment (MCI). Methods: We prospectively followed 332 participants with prevalent MCI (aged 70 years and older) enrolled in the Mayo Clinic Study of Aging for a median of 3 years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria, after reviewing neurologic, cognitive, and other pertinent data. Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Questionnaire. We used Cox proportional hazards models, with age as a time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were adjusted for sex, education, and medical comorbidity. Results: Baseline agitation, nighttime behaviors, depression, and apathy significantly increased the risk of incident dementia. We observed additive interactions between APOE ε4 and depression (joint effect HR = 2.21; 95%CI = 1.24-3.91; test for additive interaction, p < 0.001); and between APOE ε4 and apathy (joint effect HR = 1.93; 95% CI = 0.93-3.98; test for additive interaction, p = 0.031). Anxiety, irritability, and appetite/eating were not associated with increased risk of incident dementia. Conclusions: Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression, and apathy elevated the risk of incident dementia. There was a synergistic interaction between depression or apathy and APOE ε4 in further elevating the risk of incident dementia.

AB - Objective: To investigate the population-based interaction between a biological variable (APOE ε4), neuropsychiatric symptoms, and the risk of incident dementia among subjects with prevalent mild cognitive impairment (MCI). Methods: We prospectively followed 332 participants with prevalent MCI (aged 70 years and older) enrolled in the Mayo Clinic Study of Aging for a median of 3 years. The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria, after reviewing neurologic, cognitive, and other pertinent data. Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Questionnaire. We used Cox proportional hazards models, with age as a time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Models were adjusted for sex, education, and medical comorbidity. Results: Baseline agitation, nighttime behaviors, depression, and apathy significantly increased the risk of incident dementia. We observed additive interactions between APOE ε4 and depression (joint effect HR = 2.21; 95%CI = 1.24-3.91; test for additive interaction, p < 0.001); and between APOE ε4 and apathy (joint effect HR = 1.93; 95% CI = 0.93-3.98; test for additive interaction, p = 0.031). Anxiety, irritability, and appetite/eating were not associated with increased risk of incident dementia. Conclusions: Among prevalent MCI cases, baseline agitation, nighttime behaviors, depression, and apathy elevated the risk of incident dementia. There was a synergistic interaction between depression or apathy and APOE ε4 in further elevating the risk of incident dementia.

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