Combination Tx Reduces Behavioral Disturbances in Alzheimer’s Disease

graphic of brain
graphic of brain
The ASCOMALVA trial sought to decrease the frequency and severity of behavioral and psychological symptoms of dementia.

Combining donepezil with choline alphoscerate can be a beneficial alternative for reducing behavioral and psychological symptoms of dementia in patients with mild and moderate Alzheimer’s disease, a study published in Journal of Alzheimer’s Disease reported.

The ASCOMALVA (Association between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in Alzheimer’s Disease) double-blind, randomized trial conducted by members of the clinical research department at the Telemedicine and Telepharmacy Center of the University of Camerino in Italy sought to compare the cognitive effects of treatment with donepezil plus the cholinergic precursor choline alphoscerate vs donepezil only in subjects with mild or moderate Alzheimer’s disease.

This trial looked to evaluate the effects of a higher amount of acetylcholine on 4 clusters of behavioral and psychological symptoms of dementia (BPSD): mood disorders (anxiety, apathy, and depression), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of the psychiatric symptoms are attributed to a deficiency of acetylcholine. The researchers also examined the severity of caregiver distress.

Researchers measured BPSD presence and severity in 113 patients at baseline and after 24 months according to subscales of the Neuropsychiatric Inventory (NPI)2. They compared 2 groups matched for age and sex. Group A received donepezil 10 mg/d plus choline alphoscerate 1200 mg/d, while Group B received donepezil 10 mg/d plus placebo.

The NPI data reflected a significant decrease in BPSD severity and distress for the caregiver in Group A compared with Group B. The frequency and severity of mood disorders decreased in Group A, while their severity and frequency increased in Group B.

Anna Carotenub, PhD, lead researcher in the trial, said the 24-month length of the observation and treatment represented a strength of the study, while the size of the sample and “the nature of the post hoc type of data” were weaknesses. “We are also aware that the NPI score, being dependent on the caregiver input, is influenced by the caregiver mood, his burden, and his belief system,” she said.3,4 “However, this test is, up to now, one of the most widely used in clinical trials on the BPSD.”

Dr Carotenub suggested that the association of donepezil with choline alphoscerate could have positive outcomes for patients with mild and moderate Alzheimer’s disease, especially those who are unresponsive to donepezil only. “Beneficial effects should also be evaluated in terms of the reduction of other potentially dangerous drugs given for the BPSD,” she added.

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  1. Carotenuto A, Rea R, Traini E, Fasanaro AM, et al. The effect of the association between donepezil and choline alphoscerate on behavioral disturbances in Alzheimer’s Disease: interim results of the ASCOMALVA trial [published online December 30, 2016]. J Alzheimers Dis. doi: 10.3233/JAD-160675
  2. Mega MS, Masterman DM, O’Connor SM, Barclay TR, et al. The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease. Arch Neurol. 1999;56(11):1388-1393.
  3. Cummings JL, Mackell J, Kaufer D. Behavioral effects of current Alzheimer’s disease treatments: a descriptive review. Alzheimers Dement. 2008;4(1):49-60. doi: 10.1016/j.jalz.2007.10.011
  4. Grimmer T, Kurz A.Effects of cholinesterase inhibitors on behavioural disturbances in Alzheimer’s disease: a systematic review. Drugs Aging. 2006;23(12):957-967.