MCI-AD · Natural history of Mild Cognitive Impairment and Alzheimer’s Disease: factors influencing early detection, clinical course, and prognosis

Natural history of Mild Cognitive Impairment and Alzheimer’s Disease: factors influencing early detection, clinical course, and prognosis.

Aims 1-2: To identify predictors of Alzheimer's Disease (AD) in the early phase of the disease and prognostic factors in Mild Cognitive Impairment (MCI) patients. Using data on 245 memory clinic patients in Rome, we studied the occurrence of neuropsychiatric disturbances in AD patients, amnestic or multidomain MCI and 107 healthy controls. About half AD and multidomain-MCI patients had depression. Apathy was common in AD but less frequent in MCI. After apathy and depression, the most prevalent neuropsychiatric symptoms in AD and MCI were anxiety, agitation and irritability. There was an increasing prevalence of many neuropsychiatric symptoms with increasing severity of cognitive syndromes. Patients with both MCI and apathy had a sevenfold risk of AD conversion over 4 years compared to those without apathy. There was no increased AD risk in MCI patients with depression. Aim: To explore the natural history of AD. We studied 154 newly-diagnosed AD patients for 9 years to identify cognitive, demographic and clinical predictors of fast disease progression (defined as 5 point decline on Mini-Mental Status Examination (MMSE)). Rapid disease progression was more frequent in patients with younger age, higher education, global cognitive impairment and severe executive deficits. Patients with diabetes had 65% reduced risk of fast cognitive decline. We studied the impact of psychotropic drug use on the vital status of 4369 AD patients aged 60+ in Milan. Mortality over 6 years was double in patients prescribed an atypical antipsychotics compared to patients not taking antipsychotics. Risk of death in users of conventional antipsychotics was fivefold. Aim 4: To assess the occurrence of behavioral and psychological symptoms in dementia. A multi-center study was used to assess patterns of neuropsychiatric symptoms in 1015 AD patients. We used factor analysis to identify clusters of neuropsychiatric symptoms, which revealed 5 distinct syndromes: apathetic was the most common, followed by affective (anxiety and depression), psychomotor (agitation, irritability and aberrant motor behavior), psychotic (delusions and hallucinations) and a manic syndrome (disinhibition and euphoria). Most AD patients presented with 1+ syndromes. Over half had clinically significant severe symptoms. Syndrome occurrence increased with increasing dementia severity, except the affective one. We studied whether the syndromes predict disease progression; cognitive decline (5 point MMSE loss) and functional decline (a loss of 1+ activities of daily living). Patients with the affective syndrome had a twofold risk of functional decline, whereas a threefold risk of cognitive decline was associated with the manic syndrome. Conclusions and potential impact: Neuropsychiatric disturbances are common in MCI, which increase with increasing severity of cognitive impairment. Clinically, our results emphasize the need for a full psychiatric evaluation of AD patients, in addition to standard neurological exams. Apathy has an important impact on MCI progression and should be considered a mixed cognitive/psychiatric disturbance related to ongoing AD neurodegeneration. The prognostic relevance of apathy may also be relevant for the ongoing discussions on changing the criteria for early AD and MCI. Neuropsychiatric disturbances are associated with AD progression and maybe useful for prognostic planning for clinicians and patients. Patients with severe executive deficits have a worse AD prognosis, which might be due to the involvement of the prefrontal cortex in the pathological process. If the finding of a lower progression in diabetic patients is confirmed, this will contribute new insights into AD pathogenesis and disease treatment. Further, AD patients prescribed antipsychotic drugs have a high mortality risk, particularly conventional antipsychotics, which supports recent recommendation to prescribe atypical rather than conventional antipsychotics, especially in AD.

Data: CORDIS, © European Union