A 2-year follow-up of 233 very mild (CDR 0.5) Alzheimer’s disease patients (REAL.FR cohort) Fati Nourhashe ´mi 1,2 * , Pierre Jean Ousset 1,2 , Sophie Gillette-Guyonnet 1,2 , Christelle Cantet 2 , Sandrine Andrieu 2 and Bruno Vellas 1,2 1 CHU Toulouse, Ho ˆpital Casselardit, Service de me ´decine interne et ge ´rontologie clinique, Toulouse, France 2 Inserm, Toulouse, France SUMMARY Objectives Making an early diagnosis of Alzheimer’s Disease (AD) is becoming increasingly important. The Clinical Dementia Rating scale (CDR), a semi-structured interview with patient and caregiver, is a global rating scale designed for use in staging dementia. The primary objective of our study was to examine the evolution of AD in individuals with very mild AD (CDR 0.5) across a 2-year follow up. Methods A cohort of AD patients (n ¼ 682) living in the community were followed during 2 years in 16 centres of the French AD network. Each subject underwent extensive medical examination including the MMSE and CDR every 6 months. Results Two hundred and thirty-three AD patients were rated CDR 0.5 at baseline (mean MMSE score: 23.15  2.57). They were younger and reported an average duration of symptoms of approximately 0.8 years less than patients with CDR  1. During the 2-year follow-up, none of the AD CDR 0.5 subjects improved; 65% of them showed an increase in the CDR score. The rate of cognitive decline was similar between the AD CDR 0.5 and CDR  1 groups. The ADL decline was more significant in patients with CDR  1 at inclusion. Conclusions It is certainly possible to identify AD at a very early stage focusing on intra individual change in cognitive and functional impairment. Criteria with a high sensitivity and specificity for detecting AD at an early stage will help to further develop effective pharmacological and behavioural interventions for delaying the onset and progression of the disease. Copyright # 2007 John Wiley & Sons, Ltd. key words — very mild Alzheimer’s disease; CDR 0.5; dementia INTRODUCTION Alzheimer’s disease (AD), a progressive neurodegen- erative dementia, is characterized by progressive cognitive and functional deficits. In its earliest stages, AD manifests primarily as cognitive impairment. As AD progresses, there is further loss of cognitive abilities, a loss of functional independence, and the development of behavioural problems. The diagnosis of AD is currently made in patients who meet specific criteria for dementia: DSM IV (APA, 1994) and NINCDS-ADRDA criteria (McKhann et al., 1984). The identification of treatments that may be effective in slowing the decline of probable AD in its early stages has led to increasing efforts to distinguish cognitive changes predictive of AD from those that are benign. Mild Cognitive Impairment (MCI) is a clinical term describing the transitional state between normal aging and dementia (Petersen et al., 2001). It is currently the most widely used concept in classifying the cognitive impairment in the elderly that does not fulfil criteria for dementia. When confronted with a patient with a memory complaint, the issue for the clinician is not to diagnose MCI but rather to detect incipient AD. Early diagnosis and treatment may delay the onset of these symptoms. To INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2008; 23: 460–465. Published online 26 September 2007 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/gps.1904 *Correspondence to: Dr F. Nourhashe ´mi, Service de Me ´decine Interne et de Ge ´rontologie Clinique, CHU Purpan-Casselardit, 170 chemin de Casselardit, 31059 Toulouse, France. E-mail: nourhashemi.f@chu-toulouse.fr Copyright # 2007 John Wiley & Sons, Ltd. Received 6 March 2007 Accepted 8 August 2007