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Factors that predict progression in dementia are currently poorly understood. Here, Peters et al report the relationship between neuropsychiatric symptoms and progression to severe Alzheimer's dementia and death, using data from the Cache County Study. This population-based study began in 1995 and invited all Utah residents >65 years to participate. Over 5000 participants were recruited and assessed every 3–5 years. In this study, the 335 individuals diagnosed with possible or probable Alzheimer's disease were investigated and of these, 68 developed severe Alzheimer's disease during the study (1995–2010). Severe Alzheimer's dementia was defined as a Mini-Mental State Examination ≤10 or a Clinical Dementia Rating Scale score of 3 (severe). Presence of neuropsychiatric symptoms was determined using the informant-based Neuropsychiatric Inventory. Notably, >50% of participants had at least 1 neuropsychiatric symptom, with 25% having at least 1 clinically significant neuropsychiatric symptom at baseline. Multivariate Cox regression analyses (controlling for age at onset, disease duration, gender, education, general health and APOE-ε4 status) revealed that psychosis, agitation/aggression and clinically significant neuropsychiatric symptoms were predictive of progression to severe dementia and death. Presence of affective symptoms (e.g., depression) and mild neuropsychiatric symptoms were associated with earlier death only. These findings highlight the impact of neuropsychiatric symptoms on disease progression in Alzheimer's disease. Studies examining if treatment of neuropsychiatric symptoms modulates this relationship, warrant investigation. The nature and severity of neuropsychiatric symptoms in dementia varies, with these features occurring early in frontotemporal dementia. Whether a similar relationship is also observed in these non-Alzheimer's syndromes is yet to be determined.


Original languageEnglish
Pages (from-to)279-81
Number of pages3
JournalNeurodegenerative disease management
Issue number4
Publication statusPublished - Aug 2015