Anxiety and behavioural disturbance as markers of prodromal Alzheimer's disease in patients with mild cognitive impairment

Background: Depression and anxiety have been reported to be independently predictive of conversion to Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). Anxiety symptoms have been less well studied and findings in this regard have been inconsistent. The objectives of this study are to determine which symptoms among a range of neuropsychiatric symptoms known to commonly occur in patients with MCI are predictive of later conversion to AD. We also wish to determine whether these symptoms track existing measures of declining cognitive and functional status or may be considered distinct and sensitive biomarkers of evolving Alzheimer's pathology. Methods: One hundred and sixty-one patients with MCI were identified from consecutive referrals to a memory clinic. Univariate, multivariate and cox regression analyses were conducted. Results: Seventy-six per cent of all patients had at least one neuropsychiatric symptom at baseline of which anxiety (52%), affective disturbance (37%) and aggression (32%) were the most common. Increasing symptom frequency was observed with increasing clinical severity. Anticipatory anxiety and activity disturbances were significantly associated with earlier conversion to AD although this association did not remain significant following adjustment for cognitive status at baseline. Conclusion: Neuropsychiatric symptoms and anxiety symptoms in particular are common in patients with MCI. In this sample anxiety for upcoming events and purposeless activity frequently co-occurred and were significant clinical predictors of earlier conversion to AD. However, these findings were not independent of cognitive status at baseline and therefore may be markers of severity rather than independent predictors of disease progression. Copyright (C) 2010 John Wiley & Sons, Ltd.