Anna Carotenuto

Apathy in Alzheimer’s Disease: Any Effective Treatment?

Objective. This review has evaluated the effectiveness of pharmacological treatment of apathy in patients with Alzheimers disease (AD). Methods. A systematic literature search was conducted on published clinical trials assessing the effects of pharmacological treatment on apathy in AD over the last 10 years. Results. Fourteen studies considered of good quality were included in the analysis (4 randomized controlled trials, 9 open-label studies, and 1 retrospective analysis). Cholinesterase inhibitors were investigated in 9 studies, monoaminergic compounds such as methylphenidate and modafinil in two trials and one trial, respectively, and Ginkgo biloba (EGb 761 extract) and citalopram in one study each. Cholinesterase inhibitors did not show statistical significant effect in 1 RCT study but were associated to improvement in 3 open-label studies. Methylphenidate elicited a small but significant activity accompanied by relevant side effects such as high blood pressure, cough, and osteoarticular pain. EGb 761 was well tolerated and countered apathy. Other treatments induced modest improvements or were ineffective. Conclusions. Apathy treatment remains a challenge and there is no evident advantage of any specific pharmacotherapy tested so far. The development of controlled studies according to updated guidelines for the diagnosis of apathy in patients with AD is desirable.

The Psychological General Well-Being Index (PGWBI) for assessing stress of seafarers on board merchant ships.

BACKGROUND In their working activity, seafarers are exposed to high levels of stress that should be accuratelyinvestigated, measured, followed up and, if possible, countered. This is also required by regulations recently entered into force such as the Maritime Labour Convention 2006, recommending to consider special physiological or psychological problems created by the shipboard environment. The choice of the tools for this evaluation is challenging, and a common basic standard usable in a large scale should be identified. AIM The aim of this study was to evaluate: 1) the suitability of the Psychological General Well-Being Index (PGWBI) questionnaire conducted on board for assessing stress in the sailing seafarers, 2) The presenceof stress in seafarers of different categories (deck officers, engine officers, deck crew, engine crew, chiefstewards/catering staff) monitored by the PGWBI. MATERIALS AND METHODS 162 male seafarers on board of 7 tankers belonging to the same shipping companywere evaluated through the PGWB questionnaire. Analysis of variance (ANOVA) was used to analyse thedifferences in the scores of the questionnaire. RESULTS Engine officers exhibited significantly higher anxiety levels than the deck or engine crew, andshowed lower satisfaction than the deck crew. Deck and engine officers revealed higher self-control levelsthan the engine crew. Chief stewards/catering staff showed lower vitality levels than the deck crew. CONCLUSIONS Deck or engine officers should achieve a greater self-control than the crew and this is documentedby the present study. Our findings support the view that management responsibility is more often associated with higher levels of stress. In our opinion, the PGWB questionnaire is a reasonable compromise forobtaining a global evaluation of psychological conditions, including stress of seafarers. It should be therefore considered as a large scale tool for assessing the well-being and eventual stress levels of sailing seafarers.

The ASCOMALVA (Association between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in Alzheimer's Disease) Trial: Interim Results after Two Years of Treatment

Cholinesterase inhibitors (ChE-Is) are used for symptomatic treatment of mild-to-moderate Alzheimers disease (AD), but long-term effects of these compounds are mild and not always obvious. Preclinical studies have shown that combination of ChE-Is and the cholinergic precursor choline alphoscerate increases brain acetylcholine levels more effectively than single compounds alone. ASCOMALVA (Effect of association between a ChE-I and choline alphoscerate on cognitive deficits in AD associated with cerebrovascular injury) is a double-blind trial investigating if the ChE-I donepezil and choline alphoscerate in combination are more effective that donepezil alone. The trial has recruited AD patients suffering from ischemic brain damage documented by neuroimaging and has completed 2 years of observation in 113 patients of the 210 planned. Patients were randomly allotted to an active treatment group (donepezil + choline alphoscerate) or to a reference group (donepezil + placebo). Cognitive functions were assessed by the Mini-Mental State Evaluation and Alzheimers Disease Assessment Scale Cognitive subscale. Daily activity was evaluated by the basic and instrumental activities of daily living tests. Behavioral symptoms were assessed by the Neuropsychiatric Inventory. Over the 24-month observation period, patients of the reference group showed a moderate time-dependent worsening in all the parameters investigated. Treatment with donepezil plus choline alphoscerate significantly slowed changes of the different items analyzed. These findings suggest that the combination of choline alphoscerate with a ChE-I may prolong/increase the effectiveness of cholinergic therapies in AD with concomitant ischemic cerebrovascular injury.

The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer’s Disease: Interim Results of the ASCOMALVA Trial

BACKGROUND Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimers disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency. OBJECTIVE To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD. METHODS BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo. RESULTS Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group. CONCLUSIONS Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effects.

Cognitive Assessment of Patients With Alzheimer's Disease by Telemedicine: Pilot Study

Background Approximately 46.8 million people are living with dementia worldwide and their number will grow in the next years. Any potential treatment should be administered as early as possible because it is important to provide an early cognitive assessment and to regularly monitor the mental function of patients. Information and communication technologies can be helpful to reach and follow patients without displacing them, but there may be doubts about the reliability of cognitive tests performed by telemedicine. Objective The purpose of this study was to evaluate the reliability of the Mini Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog) tests administered in hospital by videoconference to patients with mild to moderate Alzheimers disease. Methods The tests were administered to 28 Alzheimers disease outpatients (8 male, mean age 73.88, SD 7.45 years; 20 female mean age 76.00, SD 5.40 years) recruited and followed in the Alzheimer’s Unit of the A Cardarelli National Hospital (Naples, Italy) at baseline and after 6, 12, 18, and 24 months of observation. Patients were evaluated first face-to-face by a psychologist and then, after 2 weeks, by another psychologist via videoconference in hospital. Results This study showed no differences in the MMSE and ADAS-cog scores when the tests were administered face-to-face or by videoconference, except in patients with more pronounced cognitive deficits (MMSE<17), in which the assessment via videoconference overestimated the cognitive impairment (face to face, MMSE mean 13.9, SD 4.9 and ADAS-cog mean 9.0, SD 3.8; videoconference, MMSE mean 42.8, SD 12.5 and ADAS-cog mean 56.9, SD 5.5). Conclusions We found that videoconferencing is a reliable approach to document cognitive stability or decline, and to measure treatment effects in patients with mild to moderate dementia. A more extended study is needed to confirm these results.

Brain volume changes in Alzheimer’s disease patients treated with a cholinesterase inhibitor plus the cholinergic precursor choline alphoscerate

Cholinergic precursors have represented the first approach recognized from a regulatory point of view to counter cognitive impairment occurring in adult-onset dementia disorders. ASCOMALVA [Effect of association between a cholinesterase inhibitor (ChE-I) and choline alphoscerate on cognitive deficits in AD associated with cerebrovascular injury] is a double-blind, controlled, randomized clinical trial investigating if the ChE-I donepezil and the cholinergic precursor choline alphoscerate in combination are more effective that donepezil alone. In this study, MRI from ACOMALVA patients were analyzed for the evaluation of brain atrophy. Participants to the ASCOMALVA trial underwent yearly MRI for diagnostic purposes. In 56 patients who achieved two years of therapy, MRI scans were analyzed by voxel morphometry techniques to assess if addition of choline alphoscerate to treatment with donepezil had an effect on brain volume changes known to occur in AD. Reference group patients (treated with donepezil alone) developed a greater atrophy of the gray and white matter compared with the group treated with donepezil plus choline alphoscerate. In the reference group a concomitant increase of the space of the cerebrospinal fluid and of the volume of the ventriculi was noticeable. One of the most affected areas was the hippocampus. Neuropsycological tests over the 24-month observation period showed in patients of the reference group a moderate time-dependent worsening in all the parameters investigated. Treatment with donepezil plus choline alphoscerate resulted in better scores of the cognitive and functional items and in an improvement in behavioural parameters, superior to that induced by donepezil alone. The above results have shown that treatment with choline alphoscerate plus donepezil versus donepezil alone counters to some extent hippocampal volume loss occurring in the brain of AD patients. The observation of a parallel improvement of cognitive and functional tests in patients treated with the cholinergic precursor loading strategy using choline alphoscerate indicates that morphological changes observed by MRI may have functional relevance.