Ba’s scientific contributions

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Figure 1: Mean errors on an object discrimination learning and t-tests, as appropriate. reversal task in aged dogs. Dogs committed significantly more For the DNMP, perfor- errors to learn the reversal task compared to the discrimination mance accuracy at each learning task. A trend for an interaction was also found which delay served as the reflected the larger increase in errors from the learning to reversal independent variable. tasks in the placebo group compared to the Novifit group. Error For discrimination and bars represent SEM. reversal learning, errors to reach the learning criterion, or total errors in cases where the learning criterion was not reached, served as independent variables. Post-hoc Fisher’s test was used as appropriate to interpret the results of the ANOVAs. Results Experiment 1: Effects of NOVIFIT Tablets in Aged Dogs DNMP: Groups were test session was administered daily which initially balanced for consisted of 20 trials. baseline DNMP accuracy and a repeated- The learning criterion for both phases measures ANOVA was conducted with treat- was identical and consisted of 2 stages. The ment group (NOVIFIT tablets and placebo) first stage required subjects to perform with serving as a between-subject variable and an accuracy of 18/20 or above on one day, with time-point (baseline and treatment), or 16/20 or above over two consecutive test and delay (5, 55, and 105 s) serving as days. The second stage required subjects to within-subject variables. A main effect of obtain a combined score of 28/40 or above delay [F(2,24)=354.9; p=0.002486] was over the next two consecutive test days. found, which was due to significantly lower Dogs were tested on both the learning and performance at the 55 and 105 s delays com- reversal phases until reaching the learning pared to the 5 s delay [p<0.05 in both cases]. criterion on both phases, or for a maximum However, no effects of treatment or time- of 30 sessions, whichever occurred earlier. point were found confirming groups did not By study design, all cats reached the learn- differ for memory performance at baseline, ing criterion on the learning phase, and or under treatment. were tested on the reversal learning phase Object Discrimination Learning and until reaching the learning criterion, or for Reversal: Cumulative errors to achieve the a maximum of 36 sessions, whichever oc- learning criterion on the learning discrimina- curred earlier. tion phase and cumulative errors to achieve Statistical Analyses the learning criterion or over a maximum of All statistical analyses were conducted us- 10 test sessions on the reversal discrimina- ing Statistica 6.0 (StatSoft, Tulsa, OK) and tion task was analyzed using a repeated- significance was set to p<0.05. The data measures ANOVA with treatment group as initially were analyzed with a repeated- a between-subject measure and with task measures analysis of variance (ANOVA) or (learning and reversal) as a within-subject variable. Significant task effects [F(1, 
Figure 2: Mean errors on an object discrimination learning and a significant effect of reversal task in aged cats. Cats committed significantly more time-point, which was errors to learn the reversal task compared to the discrimination due to an increased learning task. A trend for an interaction was also found which number of errors on reflected the fewer reversal errors under Novifit compared to the reversal learning placebo. No group differences were evident at baseline. Error bars phase compared to the represent SEM. baseline discrimination phase (F(1,14)=16.93; p=0.0011; Figure 2]. No treatment group differences were found, although there was a non-significant trend for a treatment by time-point interaction, which likely reflected the slight reduction in mean errors in the treat- ment group compared to the control group on the reversal phase (Figure 2). 10)=36.8417; p=0.000120] and an inter- A repeated-mea- action between task and treatment [F(1, sures ANOVA was then conducted with 10)=5.3846; p=0.042738] were found. The the top half performers at baseline in each task effect was due to increased errors on the treatment group. The analysis revealed reversal task compared to the initial learn- a significant effect of treatment group ing phase (Figure 1). The task by treatment [F(1,6)=11.46; p=0.015], which reflected interaction was due to fewer errors in the reduced errors under the treatment condition placebo group compared to the treatment compared to control (Figure 3). Post-hoc group on the learning phase [p=0.091100], Fisher’s revealed a significant increase in but no difference in errors between the errors on the reversal phase in the control placebo and treatment groups on the reversal subjects compared to the treatment subjects (Figure 1). [p=0.003]. By contrast, the groups did not Experiment 2: Effects of NOVIFIT differ at baseline nor did the treatment group Tablets in Aged Cats show any differences in errors between the No treatment group differences at baseline two time-points (Figure 3). were detected on discrimination learning er- A repeated-measures ANOVA was also rors, which confirmed the treatment groups conducted with the bottom half performers were adequately matched for learning at baseline in each group, but no treatment performance. Similarly, no group differ- related effects were found (Fig 4). ences were found on the practice sessions, Discussion indicating no effect of treatment on long- The current study sought to investigate if term memory. An ANOVA was conducted treatment with NOVIFIT tablets could im- examining errors with treatment group prove laboratory-based measures of cogni- (treatment and control) serving as a be- tive function in aged dogs and cats. The re- tween-subject variable and with time-point sults of these studies suggest that NOVIFIT (baseline and treatment) serving as a within- tablets improve executive function in both subject variable. The analysis revealed only species, but has no effect on either short- or 
Figure 3: Mean errors on an object discrimination learning and reversal task in top performing aged cats. The aged cats performing in the top half of each group on the baseline learning task were compared across treatment. The cats receiving Novifit committed significantly fewer errors compared to those receiving placebo. No group differences were evident at baseline. Error bars represent SEM.
Figure 4: Mean errors on an object discrimination learn- tive function. 24-26 Although ing and reversal task in low performing aged cats. The aged not investigated in the current cats performing in the bottom half of each group on the study, the putative antioxidant baseline learning task were compared across treatment. No effects of SAMe, therefore, group differences were evident at baseline or on the reversal may mediate the beneficial task. Error bars represent SEM. functional effects reported here. 16-19 Regardless, the consistency of results in both the aged dog and cat studies suggest that NOVIFIT tablets enhance age-related executive dysfunction. CONCLUSION The current study investi- gated the effects of NOVIFIT tablets, a supplement contain- ing NoviSAMe ® , on labora- tory measures of cognitive function in both aged dogs learned discrimination task to assess treat- and cats. Overall, NOVI- ment effects on long-term memory. Once FIT tablets were ineffective at improving again, no treatment differences were found. measures of short- or long-term memory. There was a trend for fewer errors on re- However, studies in both aged dogs and versal learning in cats treated with NOVI- cats consistently revealed potential benefits FIT tablets compared to placebo. When of NOVIFIT tablets on executive function. cats were divided into top or bottom half Collectively, this supports the use of NOVI- performers according to baseline learning FIT tablets for cognitive health indications performance, NOVIFIT tablets significantly in aged companion animals. Future studies reduced reversal learning errors, consistent could focus on elucidation of the mecha- with improved executive function, in the nism of action of NOVIFIT tablets or SAMe subpopulation of cats with better learn- responsible for both cognitive and behav- ing ability, but no effect was evident in the ioral improvements previously reported in poorer performers. This suggests that NOVI- companion animal aging, as well as identify- FIT tablets improve aged-related deficits in ing subpopulations of cognitively impaired executive function, but that beneficial effects pets most likely to benefit from NOVIFIT are least evident or absent in cats most af- tablet treatment. fected. ACKNOWLEDEMENTS The current studies were subject to These studies were conducted under contract individual limitations, as suggested above. from Virbac Animal Health to CanCog Future studies could employ a young sub- Technologies Inc. We would like to thank ject control group to better establish what the technicians involved in the collection of subpopulation(s) of aged subjects would these data for their professional contribution best respond to NOVIFIT tablet supplemen- and specifically Christina de Rivera for her tation. It may also be prudent to investigate contribution. the mechanism of action of NOVIFIT tablets or SAMe in future studies. We have previ- REFERENCES ously reported that antioxidant therapies in 1.  American Association of Feline Practitioners. dogs reduce oxidative stress and AD-like 2.  Senior Hempel Care H, Prvulovic Guidelines D, Revised et al. The December future of 2008. pathology in addition to improving cogni- Alzheimer’s disease: The next 10 years. Prog 
NOVIFIT ® (NoviSAMe ® ) Tablets Improve Executive Function in Aged Dogs and Cats: Implications for Treatment of Cognitive Dysfunction Syndrome
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January 2012

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Marjorie L Faubert

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Ba

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A large number of aged dogs and cats demonstrate behavioral signs consistent with a clinical diagnosis of cognitive dysfunction syndrome (CDS), which likely is a consequence of pathological brain aging. Identification of treatments that prevent, halt, or reverse CDS, therefore, represents an unmet need in senior animal veterinary care. NOVIFIT Tablets are an S-adenosylmethio-nine (SAMe) tosylate supplement currently marketed for improving cognitive health of aged dogs and cats. SAMe is an endogenous metabolite involved in several biochemical pathways, and is deficient in humans with Alzheimer's disease. The current study examined the efficacy of NOVIFIT tablets on cognitive performance enhancement in cognitive domains impaired in canine and feline aging. In the first study, aged dogs initially balanced for memory performance were divided into NOVIFIT tablet and placebo groups and tested on both the same memory task and an object discrimination learning and reversal learning task. No treatment effects on memory performance were found, but the NOVIFIT tablets-treated dogs did not show a significant increase in reversal learning errors compared to learning errors seen both under placebo and in previous aging studies, suggesting NOVIFIT tablets

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... • S-adenosyl-methionine: In trials involving cats (QS: 15) and dogs (QS: 16), SAMe supplementation improved executive functions but had no effect on learning. In cats, this benefit was observed only in the top performers [35]. A 2-month trial in pet dogs (QS: 15) also showed SAMe significantly alleviated CCD symptoms [57]. ...

Reference:

Enhancing cognitive functions in aged dogs and cats: a systematic review of enriched diets and nutraceuticals
NOVIFIT ® (NoviSAMe ® ) Tablets Improve Executive Function in Aged Dogs and Cats: Implications for Treatment of Cognitive Dysfunction Syndrome