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Predictors of progression from mild cognitive impairment to Alzheimer disease

From the Aging Research Center (K.P., A.K.B., R.M., B.W., L.B., L.F.), Karolinska Institutet, and Stockholm Gerontology Research Center, Stockholm, Sweden; and Unit of Neurology and Rehabilitation (R.M.), Laboratory of Epidemiology and Psychology of Aging and Dementia, DiNOOP, University of Palermo, Italy.

Address correspondence and reprint requests to Dr. K. Palmer, Aging Research Center, Karolinska Institutet, Gävlegatan 16, 11330, Stockholm, Sweden katie.palmer{at}ki.se

Objective: To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI).

Method: We followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria.

Results: Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk [RR] = 1.8 [1.2 to 2.7] per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 [1.0 to 3.6] per symptom).

Conclusions: The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.

Supported by grants from the Swedish Council for Working Life and Social Research (FAS), the Swedish Alzheimer Association (Alzheimerfonden), the Max Planck International Research Network on Aging (MaxnetAging), Gamla Tjänarinnor, the Loo and Hans Osterman Foundation, the Gun and Bertil Stohnes Foundation, and the Eurogendis Marie-Curie Programme (scholarship to R.M.).

Disclosure: The authors report no conflicts of interest.

Received August 11, 2006. Accepted in final form January 10, 2007.

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