Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.

These findings indicate that in patients with MCI, the patient's lack of awareness of functional deficits identified by informants strongly predicts a future diagnosis of AD. If replicated, these findings suggest that clinicians evaluating MCI patients should obtain both self-reports and informant reports of functional deficits to help in prediction of long-term outcome.

In patients with mild cognitive impairment, olfactory identification deficits, particularly with lack of awareness of olfactory deficits, may have clinical utility as an early diagnostic marker for Alzheimer's disease.

Importance Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer's disease (AD). Pharmacological treatment options, including antipsychotics are not satisfactory. Objective The primary objective was to evaluate the efficacy of citalopram for agitation in patients with AD. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability. Design, Setting and Participants The Citalopram for Agitation in Alzheimer's Disease Study (CitAD) was a multicenter, randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable AD and clinically significant agitation from eight academic centers in the US and Canada from August 2009 to January 2013. Interventions Participants (n=186) were randomized to receive a psychosocial intervention plus either citalopram (n=94) or placebo (n=92) for 9 weeks. Dose began at 10 mg/d with planned titration to 30 mg/d over 3 weeks based on response and tolerability. Main Outcomes and Measures Primary outcome measures were the Neurobehavioral Rating Scale, agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) Other outcomes were the Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), activities of daily living (ADLs), caregiver distress, cognitive safety (MMSE), and adverse events. Results Participants on citalopram showed significant improvement compared to placebo on both primary outcome measures. NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was −0.93 [95% CI: −1.80 to −0.06], p = 0.036. mADCS-CGIC results showed 40% of citalopram participants having moderate or marked improvement from baseline compared to 26% on placebo, with estimated treatment effect (odds ratio of being at or better than a given CGIC category) of 2.13 [95% CI 1.23 to 3.69], p = 0.007. Participants on citalopram showed significant improvement on the CMAI, total NPI and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (−1.05 points [95% CI: −1.97 to −0.13], p = 0.026) and QT interval prolongation (18.1 ms [95% CI: 6.1, 30.1], p = 0.004) were seen in the citalopram group. Conclusions and Relevance Among patients with probable Alzheimer's disease and agitation receiving psychosocial intervention, the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress, but cognitive and cardiac adverse effects of citalopram may limit its practical application at the 30 mg/d dose studied in this trial.

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This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimer's disease.