We present data comparing NPS in several subtypes of MCI. The prevalence of NPS in the overall cohort was similar to other published reports. For example, using the NPI-Q we report a depression prevalence of 27.3% compared to the CHS, which reported a prevalence of 20% (Lyketsos et al., 2002a
). Comparable figures for apathy are 16% in this cohort and 15% in the CHS; for irritability, the prevalence here (25%) was higher than in the CHS (15%).
The overall severity of NPS was not high (), nor were prevalences and severities in individual NPI domains (). Nonetheless we were able to observe associations between MCI subtypes and NPS: executive dysfunction (with or without associated amnestic deficits) was associated with greater NPI-Q total severity and GDS, and with worse anxiety specifically. Thus our hypoe=thesis waqs supported by these data. Although the associations were not significant after adjustment for multiple comparisons, executive dysfunction was associated with several other NPI domains including agitation, disinhibition, irritability, and sleep problems. While these associations may be due to chance, it is notable that for each of these domains the presence of executive dysfunction predicted greater severity and/or prevalence of certain NPS, suggesting a characteristic pattern of NPS associated with executive dysfunction in MCI.
We observed relatively minor differences in NPS between participants with amnestic vs. non-amnestic MCI, similar to reports from CHS (Lopez, Becker, Sweet, 2005
) and the Mayo Clinic Study of Aging (Geda et al., 2008
). These symptoms are similar to those recently proposed as characteristic of MCI (Geda et al., 2008
), of “Depression of AD” (Lyketsos et al., 2001
; Lyketsos and Olin, 2002
; Olin et al., 2002a
; Olin et al., 2002b
; Rosenberg et al., 2005
; Appleby et al., 2007
) and the syndrome of late life depression with executive dysfunction (Alexopoulos, 2002
These data suggest that the pattern of NPS in exMCI is similar to depression in AD and to the late life depression executive dysfunction syndrome. It is possible that this NPS profile is prodromal to a similar profile in AD, and its presence may signal a greater likelihood of dementia development in MCI participants. If borne out in longitudinal studies this finding would be important since NPS and particularly depression add significantly to the burden of AD for both patients and caregivers (Teri, 1997
). Identifying these symptoms at an earlier stage of disease such as MCI offers opportunities for earlier intervention. While the overall severity of symptoms is relatively low and well within the range of “subsyndromal” symptoms, it is possible that this relatively mild degree of symptom severity will predict prognosis of cognitive, functional, and neuropsychiatric symptoms. These results shed new light on the nosology and subtyping of MCI. It is possible that executive dysfunction and a characteristic NPS profile are associated with prodromal AD, and conceivably this profile might constitute a subtype of prodromal AD with implications for prognosis and treatment.
The study has several limitations including 1) limited number of neuropsychiatric measures; 2) cross-sectional design, preventing prognostic inferences; 3) and study of a referral population which may skew these results towards a more “ill” population. However, the prevalence of NPS we report is close to that found in the CHS which is a population-based sample (Lopez, Becker, Sweet, 2005
); 4) low levels of symptom severity limit generalizability of these findings, which may not be applicable to persons suffering from a primary diagnosis of major depression with co-morbid cognitive deficits. The study has several strengths including 1) very large multi-center cohort of MCI participants characterized with standardized methods; 2) clinical diagnoses of MCI and its subtypes by experienced interdisciplinary teams and current consensus-criteria.
In conclusion, we report that in a large well-characterized MCI cohort, executive dysfunction is associated with greater severity of NPS, specifically depression, anxiety, agitation, apathy, disinhibition, irritability, and sleep disturbance. These results may have implications for the treatment of MCI and its nosology, and merit follow-up longitudinal studies.