Combining Mini-Mental State Examination and Montreal Cognitive Assessment for assessing the clinical efficacy of cholinesterase inhibitors in mild Alzheimer's disease: a pilot study.

Current drugs for Alzheimer's Disease (AD), such as cholinesterase inhibitors (ChEIs), exert only symptomatic activity. Different psychometric tools are needed to assess cognitive and non-cognitive dimensions during pharmacological treatment. In this pilot study, we monitored 33 mild-AD patients treated with ChEIs. Specifically, we evaluated the effects of 6 months (Group 1 = 17 patients) and 9 months (Group 2 = 16 patients) of ChEIs administration on cognition with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Frontal Assessment Battery (FAB), while depressive symptoms were measured with the Hamilton Depression Rating Scale (HDRS). After 6 months (Group 1), a significant decrease in MoCA performance was detected. After 9 months (Group 2), a significant decrease in MMSE, MoCA, and FAB performance was observed. ChEIs did not modify depressive symptoms. Overall, our data suggest MoCA is a potentially useful tool for evaluating the effectiveness of ChEIs.

The Apathy Evaluation Scale (AES-C): Psychometric Properties and Invariance of Italian Version in Mild Cognitive Impairment and Alzheimer's Disease.

Apathy is a neuropsychiatric symptom observed in different neurological and psychiatric disorders. Although apathy is considered a symptom, it has been recently reconsidered as a syndrome characterised by three dimensions: cognitive symptoms, affective symptoms and behavioural symptoms. Recent studies have shown that apathy can be considered as a prodromal symptom of Alzheimer's disease (AD), but also an indicator of the transition from mild cognitive impairment to AD. According to this scenario, an early detection of apathy in subjects with Mild Cognitive Impairment (MCI) and Mild AD can be a valid psychometric strategy to improve an early diagnosis and promote a prompt intervention. The Apathy Evaluation Scale is a validated tool composed of 18 items that assess and quantify emotional, behavioural and cognitive aspects of apathy. The aim of this study is to assess the specific reliability and validity of the Italian version of the Apathy Evaluation Scale-Clinician Version (AES-C) to detect apathy both in amnestic MCI and mild AD patients. In the present paper, we therefore examined the psychometric properties and the invariance of the Italian Version of the AES-C conducted on a sample composed of an experimental group of amnestic MCI and AD patients (N = 107) and a control group (N = 107) constituted by Age- and Sex-matched healthy controls. Results confirm the goodness of the scale. Confirmatory factory analysis confirmed that the AES-C Italian Version presents the same stability of one second-order factor and three first-order factors identified in the original version, and all items are predicted by a single general factor. Moreover, the scale was found to be invariant across both populations. Moreover, reliability and discriminant analysis showed good values. We found in the experimental group a negative correlation between the AES-C and Frontal Assessment Battery (FAB) (rs = -0.21, p < 0.001) and Mini Mental State Examination (MMSE) (rs = -0.04, p < 0.001), while a positive correlation was found between the AES-C and Hamilton psychiatric Rating scale for Depression (HAM-D) scores (rs = 0.58, p < 0.001) Overall, our data demonstrated the validity of the Italian version of the AES-C for the assessment of apathy both in MCI and in AD patients.

New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer's disease: focus on brexpiprazole and pimavanserin.

Behavioral and psychological symptoms of dementia are symptoms of disturbed perception, mood, behavior, and thought content that occurred frequently. These symptoms, which include apathy, depression, anxiety, psychosis, agitation, and aggression, can serve as predictors of and early clinical diagnostic markers for Alzheimer's disease (AD) and are common precipitants of institutional care. Agitation and psychosis are associated with accelerated disease progression and increased tau phosphorylation in patients with AD. Current guidelines recommend the use of second-generation antipsychotics for the treatment of agitation and psychosis in AD, but only after first-line non-pharmacological interventions and for no longer than 12 weeks because long-term use of these drugs is associated with an increased risk of mortality and an increased frequency of cerebrovascular events. Therefore, new antipsychotic drugs with improved efficacy and safety are needed as an alternative to current antipsychotic drugs. In this report, we discuss some of the most relevant advances in the field of agitation and psychosis in AD and focus on the recent positive clinical evidence observed with two new antipsychotics drugs: brexpiprazole and pimavanserin. Brexpiprazole is a receptor partial agonist (D2, D3, 5-HT1A), receptor antagonist (5-HT2A/B, α1B/α2C) according to the neuroscience-based nomenclature. Two recent phase III clinical trials have shown that brexpiprazole 2 mg/day is effective for the treatment of agitation in patients with AD and has an improved tolerability and safety profile compared with currently available second-generation antipsychotics. Pimavanserin is a receptor antagonist (5-HT2A, 5-HT2C) that has been given market authorization for psychosis occurring in Parkinson's disease. Recent phase II studies suggest that this drug is effective in AD patients with more severe psychosis, although further long-term studies are needed to better define the efficacy and long-term safety profile of pimavanserin for the treatment of psychosis in AD.

Selective Serotonin Reuptake Inhibitors and Serotonin and Noradrenaline Reuptake Inhibitors Improve Cognitive Function in Partial Responders Depressed Patients: Results from a Prospective Observational Cohort Study.

BACKGROUND: Major Depressive disorder (MDD) is often accompanied by cognitive deficits, involving attention, learning, memory and executive functioning. Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs) show efficacy on affective symptoms, but it is unclear whether or not they improve cognitive symptoms. METHODS: We carried out a 12 week-prospective observational study in two cohorts of recurrent moderate-severe partial responder MDD patients, to test the hypothesis that SSRIs and/or SNRIs may affect cognitive symptoms and assess whether or not such an effect was correlated to their effect on affective symptoms. All patients underwent cognitive and neuropsychiatric assessment at baseline, 4- and 12-week follow-up. Thirty-three patients in the SSRI- and sixteen patients in the SNRI-cohort completed the follow-up. RESULTS: Both SSRIs and SNRIs reduced affective symptoms and improved global cognitive function. Both SSRIs and SNRIs improved executive function and verbal memory. Global cognitive function, verbal memory and executive function improved both in full and partial responder patients. Finally, there was no correlation between baseline Mini Mental State Examination, Montreal Cognitive Assessment and Frontal Assessment Battery scores and the mean change in Hamilton Psychiatric Rating scale for Depression or Beck Depression Inventory at the end of the 12 weeks of treatment. CONCLUSION: Present data show that SSRIs and SNRIs improve cognitive symptoms in MDD independently from their efficacy on affective symptoms. Affective and cognitive symptoms may represent distinct psychopathological dimensions of MDD with different response to antidepressant drugs.