Souvenaid Reduces Behavioral Deficits and Improves Social Cognition Skills in Frontotemporal Dementia: A Proof-of-Concept Study

Pardini, Matteo; Serrati, Carlo; Guida, Silvia; Mattei, Chiara; Abate, L; Massucco, Davide; Sassos, Davide; Amore, Mario; Cocito, Leonardo; Gialloreti, Leonardo Emberti

doi:10.1159/000369811

Cited by 37 publications

(34 citation statements)

References 16 publications

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“…In these experiments Diet2 improved both neuronal connectivity and behavioral output, suggesting a broad applicability of this nutritional technology. This, together with positive results regarding improved brain connectivity and functioning obtained in patients with AD (Scheltens et al, 2012; de Waal et al, 2014) and preliminary findings in patients with frontotemporal dementia (Pardini et al, 2015), as well as a favorable safety profile of the intervention (Cummings et al, 2017) warrant further clinical testing in other patient populations (Cummings, 2012), including PD.…”

Section: Discussionmentioning

confidence: 89%

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Perez‐Pardo

Jong

Broersen

et al. 2017

Front. Aging Neurosci.

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Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic nigrostriatal neurons, with reductions in the function and amount of dopaminergic synapses. Therefore, synapse loss and membrane-related pathology provide relevant targets for interventions in PD. We previously showed the beneficial preventive effects of a dietary intervention containing uridine and DHA, two precursors for membrane synthesis, in the intrastriatal rotenone model for PD. Here, we examined the therapeutic potential of the same dietary intervention on motor, cognitive, and gastrointestinal symptoms. In addition, we tested the effects of an extended nutritional formula based on the same precursors plus other nutrients that increase membrane phospholipid synthesis as well as prebiotic fibers. C57BL/6J mice received a unilateral rotenone injection in the striatum. Dietary interventions started 28 days after surgery, when motor-symptoms had developed. Readout parameters included behavioral tasks measuring motor function and spatial memory as well as intestinal function and histological examination of brain and gut to assess PD-like pathology. Our results show that rotenone-induced motor and non-motor problems were partially alleviated by the therapeutic dietary interventions providing uridine and DHA. The extended nutritional intervention containing both precursors and other nutrients that increase phospholipid synthesis as well as prebiotic fibers was more effective in normalizing rotenone-induced motor and non-motor abnormalities. The latter diet also restored striatal DAT levels, indicating its neurorestorative properties. This is the first study demonstrating beneficial effects of specific dietary interventions, given after full development of symptoms, on a broad spectrum of motor and non-motor symptoms in a mouse model for PD.

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Section: Discussionmentioning

confidence: 89%

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Perez‐Pardo

Jong

Broersen

et al. 2017

Front. Aging Neurosci.

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“…A total of four RCTs were included in the present meta-analysis, whereas two of those studies 29,30 were carried out with a multicomponent nutritional supplement, one with an omega-3, 32 and one 31 with a supplementation tailored for cognitive impairment. The results indicate non-significant improvement in NPI by nutritional supplementation in this group.…”

Section: Discussionmentioning

confidence: 99%

“…All four studies [29][30][31][32] In one RCT with data not meta-analyzable (NPI was given in categories), 33 the use of supplement tailored for cognitive impairment did not improve neuropsychiatric symptoms (P = 0.73).…”

Section: Effect Of Nutritional Supplementations On Neuropsychiatricmentioning

confidence: 99%

Nutritional supplements for neuropsychiatric symptoms in people with dementia: A systematic review and meta‐analysis

Haider

Schwarzinger

Štefanac

et al. 2020

Int J Geriat Psychiatry

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The aim of the present study was to assess the effects of nutritional supplementation on neuropsychiatric symptoms among people with dementia. Methods/Design: Randomized controlled trials (RCTs) were searched in the Databases PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception until January 31, 2020. Studies of RCTs carried out on people with any type of dementia who were taking nutritional supplements and had neuropsychiatric symptoms were included in this systematic review and meta-analysis. Neuropsychiatric symptoms were assessed with the validated Neuropsychiatric Inventory (NPI). Effect sizes were calculated with standardized mean differences (SMD) and 95% confidence intervals (95%CI), applying a random effect model. Results: The search yielded 1034 studies with four studies being included in the meta-analysis with a total of 377 people with dementia (mean age 69.3 [SD: 7.7] years). The diagnoses comprised mild to late Alzheimer's disease and frontotemporal dementia. Two studies included a multicomponent supplementation, one an omega-3, and one a special supplement tailored for cognitive impairment. The median follow-up was 18 weeks, with a range from 12 to 24 weeks. Pooled data showed that nutritional supplementation did not improve NPI (SMD = −0.33; [95% CI: −0.74 to 0.08]; P = 0.11; I 2 = 45%). Conclusions: The findings of this meta-analysis demonstrated no significant impact on NPI through nutritional supplementation. However, the generalization of the results is limited, as different supplements were used in different stages of dementia with a short follow-up time.

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“…Unfortunately, the management of the neuropsychiatric symptoms of bv-FTD is still challenging. Different drugs, including antipsychotics, stimulants, serotoninergic compounds and nutritional supplements [21,22] have been proposed for this purpose, albeit with modest effects. …”

Section: Discussionmentioning

confidence: 99%

Agomelatine Improves Apathy in Frontotemporal Dementia

et al. 2016

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Background/Aims: Apathy is the most common initial symptom of frontotemporal dementia (FTD) and has been linked to frontal-subcortical dopaminergic system dysfunction. No pharmacological therapy has been approved for the treatment of apathy, but, on the basis of its physiopathological mechanism, we suspected that increasing prefrontal dopaminergic innervation could improve this disabling symptom. Methods: We evaluated a group of 24 nondepressed patients with a diagnosis of the behavioral variant of FTD, in order to determine the effectiveness on apathy of agomelatine, an antidepressant with MT1 and MT2 receptor agonism and 5-HT2C receptor antagonism; the latter leads to an increase in prefrontal dopaminergic and noradrenergic tone. To try to tease out the effects of 5-HT2C antagonism on apathy, patients were randomized, using a cross-over design, to receive either agomelatine 50 mg/day or sustained release melatonin 10 mg/day for 10 weeks in a double-blind procedure. At the end of the follow-up period, subjects receiving melatonin switched to agomelatine for the following 10 weeks. Results: Agomelatine, but not melatonin, was associated with a significant reduction of apathy in FTD subjects and of caregiver distress due to patients' apathy. The switch from melatonin to agomelatine was associated with a reduction in apathetic behavior. Agomelatine was well-tolerated by all enrolled subjects. Conclusions: Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients.

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Souvenaid Reduces Behavioral Deficits and Improves Social Cognition Skills in Frontotemporal Dementia: A Proof-of-Concept Study

Cited by 37 publications

References 16 publications

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease

Nutritional supplements for neuropsychiatric symptoms in people with dementia: A systematic review and meta‐analysis

Agomelatine Improves Apathy in Frontotemporal Dementia

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