Alzheimer's disease : modernizing concept, biological diagnosis and therapy. Alzheimer disease : neuropsychology and pharmacology. Alzheimer Disease : Neuropsychology and Pharmacology. All rights reserved. Remember me on this computer. Cancel Forgot your password? Showing all editions for 'Alzheimer disease : neuropsychology and pharmacology'. Year 1 7 2 Language English 9 German 1. Alzheimer's disease : modernizing concept, biological diagnosis and therapy by H Hampel; M C Carrillo;. Print book.
Alzheimer disease : neuropsychology and pharmacology by ; et al. Alzheimer disease : neuropsychology and pharmacology by C Durlach;. The LipiDiDiet group is a research consortium, which has studied the preclinical and clinical impact of nutrition in AD. This research contributed to the development of the medical food Souvenaid Nutricia, Zoetermeer, the Netherlands.
These nutrients were selected based on their biological properties, involved in metabolic pathways Kennedy and PEMP pathways , and specifically combined to enhance efficacy in phospholipid turn over and improvement of synaptic formation. In animal models, including transgenic AD mice, dietary intervention with this multinutrient combination has been shown to enhance phospholipid synthesis, to maintain white and gray matter integrity, to reduce the impact of amyloid-induced neurodegeneration and loss of functional connectivity, to increase numbers of hippocampal cholinergic synapses, and to improve cholinergic neurotransmission and hippocampus-dependent cognitive performance [ 17—26 ].
In two previous randomized clinical trials, Souvenaid improved memory performance in patients with mild AD, over 3 and 6 months, respectively [ 28, 29 ]. Furthermore, increased neurophysiological measures of synaptic activity, and enhanced functional connectivity in the brain [ 30 ] were reported in the longer study.
Another study in patients with more advanced AD, who were on stable AD medication, showed no significant add-on effect of the multinutritional intervention [ 31 ]. Across four clinical trials, Souvenaid was well tolerated with a positive safety profile, alone and in combination with cholinesterase inhibitors and memantine.
The results of the clinical trials of Souvenaid are consistent in their report of benefits in cognition and memory with better outcomes in earlier intervention [ 16 ]. The size effect of this nutritional intervention has been published recently [ 32 ]. Small to moderate effect sizes have been observed on primary outcome memory function in patients with mild AD in two separate randomized controlled trials [ 28, 29 ].
These effect sizes are clinically detectable and similar to those seen in cholinesterase inhibitors. TC [ 33 ]. In this present study, the mode of action of the specific multinutrient combination is further explored using 18 F-fluoro-deoxyglucose 18 F-FDG-PET and neuropsychological tests in clinical practice. The results of one trial using EEG suggest that Souvenaid preserves the organization of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD.
This result strengthens the hypothesis that Souvenaid affects synaptic integrity and function [ 34 ]. In this work, we want to replicate the results obtained by Souvenaid in this trial preserving the organization of brain networks using FDG-PET, a technique that is a direct index for synapse function and density because the uptake of 18 F-FDG is driven by synaptic terminals generating ATP for synthesis, release, and recycling of neurotransmitters, the maintenance of the normal resting potential, and the recovery from action potentials [ 35, 36 ].
For diagnosis of MCI, impairment in one or more cognitive domains has to be present, based on clinical interpretation of performances on a neuropsychological test battery Barcelona brief version battery [ 38 ], whereas independency of functional abilities is preserved. Scans were divided into normal, mild temporal low glucose metabolism LGM uni- or bilateral , medium temporo-parietal LGM unilateral , and high temporo-parietal LGM bilateral. Those who refused were included in control group.
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Some patients in the prodromal phase of the disease were given cholinesterase inhibitors as a primary treatment. This longitudinal study, with a 1-year follow-up, was carried out from June to December in the Neurology Department of Infanta Cristina Hospital, Madrid, Spain. Baseline demographic information, including age, sex, education, family history of AD, date of diagnosis MCI or dementia, and rate of progression to dementia, was recorded.
All patients had a neurological history, physical examination, neurological examination, neuropsychological test exploration, CT scans, blood samples including total protein levels , and 18 F-FDG-PET imaging. Neuropsychological tests and 18 F-FDG-PET imaging were conducted at the inclusion visit, approximately 8 months later, and checked again at the 1-year follow-up dependent on the delay in clinical visit.
Age-Related Changes of Adaptive and Neuropsychological Features in Persons with Down Syndrome
On the last clinical visit, we included a neurological examination and the Subjective Changing Scale SCS completed by the caregiver. The analysis was visual. Cognitive measures were made according to the Barcelona battery brief version which included orientation, memory, language, executive functions, gnosis, and praxis domains. This battery was administered once at baseline and then repeated 8 months later. Patients included in high performance group were excluded from the study.
A descriptive analysis was performed.
Several potential covariates and possible intervention effect moderators were defined: Mini-Mental State Examination at screening, diagnosis of dementia, relevant medical events, relevant medication, coexisting diseases, all the demographic and other baseline variables, and product compliance. The main reasons for dropout were negative to intake. Two patients refused neuropsychological NPS examination one in each group. Mean age was The age of the participants at the beginning of the study was the same between groups Fig.
Cardiovascular risk factors. HTA, hypertension; DM, diabetes mellitus. In neuropsychological testing, each cognitive domain was evaluated. There were no differences between groups, comparing ST monotherapy with WT. ST, Souvenaid treatment; WT, without treatment. There were no significant differences in the rate of progression to dementia between groups.
This study aims to explore the effect of Souvenaid on cerebral glucose metabolism in mild to very mild patients with high risk of progression to AD, using neuropsychological variables, and 18 F-FDG scans over 1 year of follow up and in real life clinical practice. A positive effect of the nutritional intervention was observed, compared with controls, in cognitive and imaging parameters but not in progression to dementia.
These results are in line with previous trials of Souvenaid in early AD [ 16 ].get link
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This is the first Souvenaid study to include functional neuroimaging. The LipiDiDiet group, a research consortium, has studied preclinical and clinical impacts of nutrition in AD. This research contributed to the development of the medical food Souvenaid Nutricia; Zoetermeer, the Netherlands. The active component of Souvenaid includes, in addition to other nutrients e.
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The omega-3 fatty acid and choline are true nutrients: their consumption in foods raises their levels in the blood and brain [ 20, 21 ]. In contrast, the uridine in the blood of adult humans is more like a hormone than a nutrient, in that it is derived not from dietary sources but from synthesis in and secretion from the liver [ 20, 21 ]. This is because most of the uridine in foods is present in a form e. These three compounds are essential precursors in the biosynthesis of the phosphatide molecules that comprise the bulk of synaptic membranes phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol.
The key biochemical steps in the conversions of DHA or EPA, choline, or uridine to the phosphatides are all catalyzed by enzymes which have low affinities for their substrates [ 20 ]. Thus, administering each substrate increases the saturation of its metabolizing enzyme and the rate at which new product is formed, ultimately raising brain phosphatide levels [ 19 ]. Hence both of the key constituents phospholipids and proteins of functionally-complete membranes are formed when animals or humans receive the three precursors.
This, in turn, enhances the production of dendritic spines [ 25 ], the immediate cytologic precursor of new synapses, thereby partly correcting the deficiency in the spines that is characteristic of AD and other dementias [ 26 ], and enabling enhanced synaptogenesis. In animal models, including transgenic AD mice, administration of the three precursors, alone or as a constituent of Souvenaid, has also been shown to maintain the integrity of white and gray matter, reduce the loss of functional connectivity, increase cholinergic hippocampal synapses and cholinergic neurotransmission, and facilitate hippocampus-dependent cognitive performance [ 17—26 ].
A previous clinical study in patients with mild AD using EEG as a biomarker demonstrated an effect of the multinutrient combination on functional connectivity and brain network organization, suggesting that its mode of action includes alteration of synapse function [ 39 ]. As with all real-world studies, this has some limitations. The first one is the brief neuropsychological test battery used for the study, and the other is the visual assessment of 18 F-FDG-PET scans. Secondly, in the 5 patients with bi-therapy ST and cholinesterase inhibitors , compared with the other monotherapy or WT , there were no differences in the values, only in the rate of progression to dementia.
Obviously, these patients were more impaired although MCI criteria , therefore it was right to begin treatment sooner, with both therapies ST and cholinesterase inhibitors. Interestingly, these patients progressed to dementia more quickly. Another thing to consider is the option of to treat or not. We offered the treatment to everybody.