Neuropsychiatric Predictors of Progression from Amnestic-Mild Cognitive Impairment to Alzheimer's Disease: The Role of Depression and Apathy

Abstract

Abstract. The aim of the study is to evaluate whether depression or apathy in patients with amnestic-mild cognitive impairment (MCI) increases the risk of progressing to Alzheimer's disease (AD). We investigated 131 consecutive memory-clinic outpatients with newly-diagnosed amnestic-MCI (mean age 70.8, SD = 6.5). Psychiatric disorders were diagnosed at baseline according to the criteria for depression and apathy in AD. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory (NPI). Follow-up examinations were conducted after six months and annually for four years. Neurologists diagnosed AD at follow-up using NINCDS-ADRDA criteria. Cox proportional hazard models with 95% confidence intervals were used to test the hypothesis that apathy or depression increases the risk of developing AD. At baseline, 36.6% amnestic-MCI patients had a diagnosis of depression and 10.7% had apathy. Patients with both amnestic-MCI and an apathy diagnosis had an almost sevenfold risk of AD progression compared to amnestic-MCI patients without apathy (HR = 6.9; 2.3-20.6), after adjustment for age, gender, education, baseline global cognitive and functional status, and depression. Furthermore, the risk of developing AD increased 30% per point on the NPI apathy item (HR = 1.3; 1.1-1.4). There was no increased risk of developing AD in amnestic-MCI patients with either a diagnosis or symptoms of depression. In conclusion, apathy, but not depression, predicts which patients with amnestic-MCI will progress to AD. Thus, apathy has an important impact on amnestic-MCI and should be considered a mixed cognitive/psychiatric disturbance related to ongoing AD neurodegeneration.

A Novel Assessment and Profiling of Multidimensional Apathy in Alzheimer’s Disease

“…The largest of these groups was the Executive and Initiation apathy subgroup (N=43), which was reinforced by people with AD and controls self-rating group comparison and magnitude of difference between the Executive and Initiation apathy subscales. As one of the most prominent behavioral symptoms in AD, cognitive impairment is also associated with apathy [45][46][47]. While memory impairment is common in AD, attention [48] and executive dysfunction [49], such as planning, spatial navigation attention [50][51][52] and verbal fluency [53] are also particularly noted to be impaired as the disease progresses to later stages, which is particularly relevant to our sample which is more impaired.…”

Proinflammatory cytokines, sickness behavior, and Alzheimer disease

“…32 In addition, subjects with mild cognitive impairment show a NPI profile that is remarkably similar to that associated with sickness behavior, 33 suggesting that the early presentation of these symptoms might represent the neurochemical consequences of microglial activation and consequently explain their poor cognitive outcome. 34 …”

Modifiable Predictors of Dementia in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

“…In the largest study, reporting apathy symptoms but not depressive symptoms on the relevant validated Geriatric Depression Score (GDS)-15 subscales 55 predicted conversion from aMCI to AD, but apathy symptoms alone were not a significant predictor (Figure 2e). Results from four other small studies were mixed; NPI apathy subscale scores and apathy assessed using standard criteria was associated with conversion from aMCI to AD 56 with a similar but non-significant trend reported in a second study 57 . Two small studies examined whether apathy predicted conversion from any type MCI to all cause dementia.…”