Neuropsychiatric symptoms, APOE ε4, and the risk of incident dementia

Abstract

Objective: To investigate the population-based interaction between a biological variable (APOE e4), 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 e4 and depression (joint effect HR 5 2.21; 95% CI 5 1.24-3.91; test for additive interaction, p , 0.001); and between APOE e4 and apathy (joint effect HR 5 1.93; 95% CI 5 0.93-3.98; test for additive interaction, p 5 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 e4 in further elevating the risk of incident dementia. Dementia is one of the leading causes of morbidity and mortality in late life. It presents several challenges, not least of which are the economic consequences.1 Therefore, it is critical to prevent or delay dementia.2 Identification of high-risk groups is a key step toward the prevention of dementia. Mild cognitive impairment (MCI) is the intermediate stage between cognitive aging and dementia and is associated with an increased risk of dementia. Clinic-based samples have indicated that neuropsychiatric symptoms in prevalent MCI increase the risk of incident dementia.4-6 However, only a few studies were derived from population-based settings. 7,8 In addition, studies derived from clinical samples including our own team have reported the synergistic interaction between a neuropsychiatric symptom (e.g., depression) and APOE e4 in increasing the risk of incident dementia. 9-11While APOE e4 and neuropsychiatric symptoms are independent risk factors for incident dementia, little is known about the interaction between APOE e4 and a broad spectrum of neuropsychiatric symptoms in increasing the risk of incident dementia in a population-based

The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations

“…NPS are common in Mild Cognitive Impairment (MCI), and are associated with poorer cognitive and psychosocial function within MCI cohorts [13, 14]. Population-based [15, 16] as well as clinic-based cohort studies [17] provide consistent evidence that NPS in MCI are associated with higher risk for incident dementia, with an estimated annual rate of progression to dementia of 25% for MCI plus NPS [17] in contrast to the rate for MCI of 10 to 15 % per year [18]. Similarly, NPS in older adults with normal cognition confers a higher likelihood of progression to MCI and dementia, as shown in the Alzheimer’s Disease Cooperative Study [19], one Alzheimer’s Disease Research Center [20], the Danish Psychiatric and Somatic Health Register [21], the Mayo Clinic Study of Aging [22], the Medical Research Council Cognitive Function and Ageing Study [23] and the National Alzheimer’s Coordinating Center database [24, 25].…”

Neuropsychiatric Symptoms and Cognitive Impairment: Understanding the Importance of Co-Morbid Symptoms

“…It is well accepted that the comorbid presentation of NPS in MCI is linked to higher progression to dementia [9][10][11][12][13][14][15] and that for patients with Alzheimer's disease (AD), NPS are associated with an increased likelihood of progression from mild to severe dementia [16].…”

Depressive and anxiety symptoms and cortical amyloid deposition among cognitively normal elderly persons: the Mayo Clinic Study of Aging

“…However, studies have found an association between amyloid deposition with a faster cognitive decline in both cognitively normal elderly (Chetelat et al , 2012; Knopman et al , 2012; Morris et al , 2009; Petersen et al , 2016) and MCI subjects (Jack et al , 2010; Jagust et al , 2010). A growing body of research has shown that depressive and anxiety symptoms may increase the risk of cognitive decline (Geda et al , 2006; Geda et al , 2008; Geda et al , 2014; Pink et al , 2015). Furthermore, we and others have reported that depressive (Donovan et al , 2015; Krell-Roesch et al , 2016) and anxiety symptoms (Pink et al , 2017) are associated with neuroimaging biomarkers of AD, specifically FDG-PET and cortical thickness as measured by MRI, among cognitively normal elderly participants.…”