![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,](https://www.researchgate.net/profile/Gary-Landsberg/publication/280075512/figure/fig1/AS:284539793494029@1444850981807/Mean-errors-on-an-object-discrimination-learning-and-t-tests-as-appropriate-reversal_Q320.jpg)
![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](https://www.researchgate.net/profile/Gary-Landsberg/publication/280075512/figure/fig2/AS:284539793494030@1444850981871/Mean-errors-on-an-object-discrimination-learning-and-a-significant-effect-of-reversal_Q320.jpg)
Content uploaded by Gary M Landsberg
Author content
All content in this area was uploaded by Gary M Landsberg on Jul 15, 2015
Content may be subject to copyright.
A preview of the PDF is not available
NOVIFIT ® (NoviSAMe ® ) Tablets Improve Executive Function in Aged Dogs and Cats: Implications for Treatment of Cognitive Dysfunction Syndrome
Abstract and Figures
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
Figures - uploaded by Gary M Landsberg
Author content
All figure content in this area was uploaded by Gary M Landsberg
Content may be subject to copyright.
... Taylor et al. of environmental enrichment (23%), and one used a training intervention (0.03%) ( Table 2). Dietary changes, focusing on the use of antioxidant-rich diets and omega-3 fatty acid supplementation known for their neuroprotective effects (Lee et al., 2020), were shown to reduce oxidative stress and improve cognitive function (Amano et al., 2022;Araujo et al., 2012Araujo et al., , 2008Araujo et al., , 2022Benedetti et al., 2019;Chapagain et al., 2020;Christie et al., 2009;Dodd et al., 2003Dodd et al., , 2002Hadley et al., 2017;Heath et al., 2007;Milgram et al., 2007Milgram et al., , 2002Milgrama et al., 2004;Milgramb et al., 2004;Nippak et al., 2007;Osella et al., 2007;Pan, Kennedy, et al., 2018;Pan, Landsberg, et al., 2018;Pan et al., 2010;Pero et al., 2019;Pop et al., 2010;Reichling et al., 2006;Siwak et al., 2005;Snigdha et al., 2012Snigdha et al., , 2016. Fig. 2 shows the categories of ingredients for the supplements tested. ...
... Improvements in ability were often seen in one domain or at one task but not another (Davis et al., 2017;Pan, Kennedy, et al., 2018;Siwak et al., 2005). For example, the supplement Novifit® had no impact on memory function but reduced errors in reversal learning (Araujo et al., 2012). Another combined supplement led to improved performance on easier discrimination tasks but not on the more complex (Siwak et al., 2005). ...
... 53 Laboratory studies assessing executive function, attention, and memory impairment have documented cognitive function decline in cats using a neuropsychological test apparatus. [54][55][56][57] These tests also provide a mechanism for assessing the effects of therapeutic agents on several different cognitive domains. In fact, although owners most commonly begin to recognize and report signs associated with CDS at 9 to 11 years and older 5,9,38 using a standardized test apparatus, an age-related decline in cognitive function has been demonstrated in cats as early as 6 to 7 years of age. ...
... A study in aged cats given SAMe demonstrated improvement in cats with mild impairment but not the most impaired cats. 56 Nutraceutical supplementation including Senilife (CEVA Animal Health, Lenexa, KS, USA) 94 containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine and Aktivait (VetPlus, Lytham, UK) 95 containing omega-3 fish oils, vitamin C and E, Lcarnitine, and alpha-lipoic acid have demonstrated some positive effects in dogs but not in cats. The dog version of Aktivait contains alpha-lipoic acid but not in the cat product because alpha-lipoic acid is toxic to cats. ...
... • 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]. ...
With advancements in veterinary care and the growing recognition of pets as integral member of the family, the lifespans of dogs and cats have significantly increased, leading to a higher prevalence of age-related conditions, including cognitive dysfunction syndrome (CDS). CDS adversely impacts pets’ quality of life and presents emotional and practical challenges for owners. Given its similarities to Alzheimer’s disease in humans, CDS has gained attention as a target for nutrition-based interventions aimed at preserving cognitive function. This systematic review evaluates the efficacy of enriched diets and nutraceuticals in improving cognition in aging companion animals. A literature search was conducted using PubMed, CAB Abstracts, Web of Science, and Dimensions to identify clinical trials published in English that investigated the effects of enriched diets or nutraceuticals on cognitive functions in aged cats or dogs. Study quality was assessed using a modified CAMARADES checklist. A total of 30 studies (27 canine and 2 feline trials) published between 2002 and 2023 were reviewed. Studies on enriched diets generally demonstrated higher methodological quality compared to those on supplements. Omega-3 fatty acids showed cognitive benefits in aging pets, especially at higher doses, while antioxidants from plant extracts and products and vitamins E and C alone were less effective but remain essential for stabilizing omega-3 fatty acids. Other supplements, including S-adenosyl methionine, medium-chain triglycerides, homotaurine, and apoaequorin, also showed promise. However, future studies must standardize protocols, include robust control groups, and utilize both objective tasks and subjective questionnaires to strengthen conclusions.
This chapter includes treatments that do not require a prescription and are most often sold over the counter. Pheromone-based treatments such as dog-appeasing pheromone, nutraceuticals such as α-casozepine, α-lactalbumin, l-tryptophan, and various dietary supplements will be discussed.
Phytotherapy, aromatherapy, Bach flowers, and homeopathy are also discussed in this chapter. Finally, a summary table with the level of scientific evidence for each over-the-counter treatment closes this section and will allow the practitioner to better orient his therapeutic choices.
Research into cognition in cats and the impact of nutrition on cat cognitive health lags behind that in dogs but is receiving increased attention. In this review, we discuss the evolutionary history of the domesticated cat, describe possible drivers of domestication, and explore the interrelationships between nutrition and cat cognition. While most cat species are solitary, domesticated cats can live in social groups, engage in complex social encounters, and form strong attachments to humans. Researchers have recently started to study cat cognition using similar methods as those developed for dogs, with an initial primary focus on perception and social cognition. Similar to dogs, cats also show cognitive and behavioral changes associated with stress and aging, but these signs are often gradual and often considered a consequence of natural aging. Despite the fundamental role of nutrition in cognitive development, function, and maintenance, research into the association between nutrition and cognition in cats is only preliminary. Ultimately, additional research is needed to gain a full understanding of cat cognition and to explore the role of nutrition in the cognitive health of cats to help improve their welfare.
Background
Canine cognitive dysfunction (CCD) is a common, yet underdiagnosed neurodegenerative disease affecting older dogs. Treatment is most effective when started early, so identifying mild cognitive decline in the earlier stages of the disease is considered important.
Hypothesis/objective
To compare the results of three different standard screening questionnaires [Canine Dementia Scale (CADES), Canine Cognitive Assessment Scale (CCAS), and Canine Cognitive Dysfunction Rating Scale (CCDR)] for CCD diagnosis. Trainability, pain sensitivity, and fear were additionally assessed with the Canine Behavioral Assessment and Research Questionnaire (C-BARQ) in order to evaluate associations between the three dementia scales and behavior.
Methods
An online survey containing all the mentioned questionnaires was designed for and distributed among owners of elderly dogs.
Results
Data from 597 dogs were analyzed. Overall, the scores of the three CCD questionnaires correlated well with each other, especially those of the CADES and CCAS. The CADES was more sensitive in identifying dogs with already mild to moderate cognitive impairment, while the others classified them as still undergoing normal aging. CCD scores increased for all questionnaires with age with spatial orientation being a key feature in CCD development. Trainability assessed with the C-BARQ decreased significantly with severity of CCD signs, while pain sensitivity increased. Fear and anxiety was pronounced in animals with mild but not with severe CCD. These associations based on the C-BARQ were more clearly observable in relation to CADES and CCDR than CCAS.
Conclusion/clinical relevance
The choice of screening questionnaire impacts the evaluation of cognitive status and severity of CCD. Thresholds for severity classification differ significantly and may have an impact on reliable assessment. Further longitudinal studies are required to determine which of the questionnaires investigated in this study is best suited for early detection of CCD.
Simple Summary
Canine cognitive dysfunction is considered the canine equivalent to human Alzheimer’s disease. It is a growing concern in veterinary medicine, as it affects many aged dogs. Dietary intervention with different diets and supplements may improve clinical signs and prevent further degeneration. Using an online questionnaire, we found that even though few owners were willing to change their dog’s main diet, many of them added supplements such as oils and vitamins. Consulting a veterinary surgeon when using dietary supplements is important as it allows for evidence-based recommendations to be made.
Abstract
Canine cognitive dysfunction (CCD) is becoming increasingly recognized in veterinary medicine, as dogs live longer and with CCD being highly prevalent among the elderly dog population. Various studies have shown that diet and dietary supplementation can positively influence the clinical signs of CCD, especially if given at an early stage. The aim of this study was to investigate owner use of dietary supplements (DSs) in dogs with age-related behavioral changes. An observational study based on an online questionnaire for owners of dogs with age-related behavioral changes was performed. Out of a total of 394 owners who completed the survey, after noticing age-related behavioral changes, over half of the dogs received DSs (54%), whereas only 8% reported changing their dog’s base diet. The most used DS was fish oil (48%). The use of DSs should be discussed with and monitored by veterinary surgeons since many geriatric patients have multi-morbidities, may have specific nutritional requirements and receive multi-faceted medications.
The present review focuses on the utility of a canine model in evaluating nutritional interventions for age-related cognitive dysfunction. Aged dogs demonstrate progressive cognitive decline with concurrent amyloid-beta pathology that parallels the pathology observed in aging humans. Dogs, therefore, provide a natural model of human pathological aging. We have and are in the process of evaluating several nutritional-based interventions aimed at preventing cognitive decline and brain aging. In a three-year longitudinal study, we examined the effects of a diet enriched with antioxidants and mitochondrial cofactors on several measures of cognition and brain aging. Compared to controls, aged dogs on the enriched diet demonstrated both short- and long-term cognitive benefits, as well decreased deposition of amyloid-beta protein. The diet also reduced behavioral signs associated with canine Cognitive Dysfunction Syndrome when assessed in veterinary clinical trials. We also have preliminary evidence suggesting a beneficial effect of a proprietary blend of docosahexaenoic acid and phospholipids on both cognitive and physiological measures. Collectively, our data indicate (1) that the dog, either in the laboratory or in the clinic, provides an important tool for assessing nutritional interventions and (2) that combination interventions aimed at several mechanisms of pathological aging may prove more effective than single nutritive components in human trials.
Aging has been shown to disrupt performance on tasks that require intact visual search and discrimination abilities in human studies. The goal of the present study was to determine if canines show age-related decline in their ability to perform a novel simultaneous visual search task. Three groups of canines were included: a young group (N = 10; 3 to 4.5 years), an old group (N = 10; 8 to 9.5 years), and a senior group (N = 8; 11 to 15.3 years). Subjects were first tested for their ability to learn a simple two-choice discrimination task, followed by the visual search task. Attentional demands in the task were manipulated by varying the number of distracter items; dogs received an equal number of trials with either zero, one, two, or three distracters. Performance on the two-choice discrimination task varied with age, with senior canines making significantly more errors than the young. Performance accuracy on the visual search task also varied with age; senior animals were significantly impaired compared to both the young and old, and old canines were intermediate in performance between young and senior. Accuracy decreased significantly with added distracters in all age groups. These results suggest that aging impairs the ability of canines to discriminate between task-relevant and -irrelevant stimuli. This is likely to be derived from impairments in cognitive domains such as visual memory and learning and selective attention.
Increased plasma homocysteine levels have been described as an independent risk factor for Alzheimer's disease (AD), but the underlying pathophysiology is unclear.
This single-center, cross-sectional, correlational study analyzed homocysteine metabolism in 60 AD patients and 60 control subjects.
Fasting plasma levels of vitamin B₁₂, folate and homocysteine as well as cerebrospinal fluid (CSF) levels of folate derivates, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine were measured. In addition, the apolipoprotein E (APOE) genotype was determined.
As expected, the APOE4 allele was significantly overrepresented in AD patients compared with controls (p < 0.001). Homocysteine plasma levels in the highest quartile were more frequent in the AD patients than in the controls (p = 0.008). In addition, AD patients had significantly lower CSF levels of the methyl group donor SAM (193 ± 31 vs. 207 ± 37 nmol/l; p = 0.032). Accordingly, the SAM/SAH ratio, which represents the methylation capacity, was significantly lower in the CSF of the AD patients (7.6 ± 2.4 vs. 9.1 ± 2.8; p = 0.003). Further, explorative analysis of all subjects showed that CSF SAM levels were lower in carriers of the APOE4 allele compared with noncarriers (189 ± 30 vs. 207 ± 36 nmol/l; p = 0.010). Of the individuals with CSF SAM levels in the lowest quartile, 63% carried the APOE4 allele compared with 17% of the individuals with CSF SAM levels in the highest quartile (Pearson: χ² = 9.9; p = 0.002; odds ratio 0.126, 95% confidence interval 0.32-0.49).
These data suggest that AD is associated with lower CSF SAM levels and that this is at least partly due to an association of the APOE4 allele with reduced SAM levels in the CSF.
The present study focused on the hypothesis that dietary supplementation with medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing the brain with energy in the form of ketones. Aged Beagle dogs were subjected to a baseline battery of cognitive tests, which were used to establish cognitively equivalent control or treatment groups. The dogs in the treatment group were maintained on a diet supplemented with 5.5 % MCT. After an initial wash-in period, all the dogs were tested with a battery of cognitive test protocols, which assessed sequentially landmark discrimination learning ability, egocentric visuospatial function and attention. The groups were maintained on the diets for 8 months. The MCT-supplemented group showed significantly better performance in most of the test protocols than the control group. The group differences also varied as a function of task difficulty, with the more difficult task showing greater supplementation effects than the easier tasks. The group given the MCT supplement showed significantly elevated levels of beta-hydroxybutyrate, a ketone body. These results indicate, first, that long-term supplementation with MCT can have cognition-improving effects, and second, that MCT supplementation increases circulating levels of ketones. The results support the hypothesis that brain function of aged dogs can be improved by MCT supplementation, which provides the brain with an alternative energy source.
A growing body of evidence indicates that nutritional supplements can improve cognition; however, which supplements are effective remains controversial. In this review article, we focus on dietary supplementation suggested for predementia syndromes and Alzheimer's disease (AD), with particular emphasis on S-adenosylmethionine (SAM) and polyunsaturated fatty acids (PUFA). Very recent findings confirmed that SAM can exert a direct effect on glutathione S-transferase (GST) activity. AD is accompanied by reduced GST activity, diminished SAM, and increased S-adenosylhomocysteine (SAH), the downstream metabolic product resulting from SAM-mediated transmethylation reactions, when deprived of folate. Therefore, these findings underscored the critical role of SAM in maintenance of neuronal health, suggesting a possible role of SAM as a neuroprotective dietary supplement for AD patients. In fact, very recent studies on early-stage AD patients and moderate- to late-stage AD patients were conducted with a nutriceutical supplementation that included SAM, with promising results. Given recent findings from randomized clinical trials (RCTs) in which n-3 PUFA supplementation was effective only in very mild AD subgroups or mild cognitive impairment (MCI), we suggest future intervention trials using measures of dietary supplementation (dietary n-3 PUFA and SAM plus B vitamin supplementation) to determine if such supplements will reduce the risk for cognitive decline in very mild AD and MCI. Therefore, key supplements are not necessarily working in isolation and the most profound impact, or in some cases the only impact, is noted very early in the course of AD, suggesting that nutriceutical supplements may bolster pharmacological approaches well past the window where supplements can work on their own. Recommendations regarding future research on the effects of SAM or n-3 PUFA supplementation on predementia syndromes and very mild AD include properly designed RCTs that are sufficiently powered and with an adequate length (e.g., 3-5 years of follow-up).
Physical signs of old age may be obvious, but mental and cognitive changes require more careful observation. Changes in behavior may represent the earliest indications of medical problems, or disorders of the central nervous system, and these may be bidirectional. Cognitive dysfunction syndrome is underdiagnosed and affects a substantial portion of aged companion animals. This article describes potential treatment regimens to address age-related behavioral problems, as well as a framework for investigating differential diagnoses. Early identification of changes in behavior is essential for the adequate treatment and management of medical and behavioral problems, and for monitoring outcomes.
Practical relevance:
Cognitive dysfunction syndrome (CDS) is a widely accepted diagnosis in dogs, with established treatment options. In cats, however, our understanding of cognitive dysfunction is still being shaped by ongoing research in the field, and limited treatment options are available. Recent clinical studies indicate that old age in the cat is accompanied by increased behavioural signs such as wandering, vocalization and night-time activity that are not attributable to identifiable medical problems. It is essential, therefore, that veterinarians include behavioural well-being in the routine care of senior cats.
Patient group:
While the exact age of onset is not established, studies suggest that age-related behavioural changes consistent with cognitive dysfunction are prevalent in cats as early as 10 years of age and that prevalence increases significantly in older cats.
Clinical challenges:
The diagnosis of cognitive dysfunction requires the identification of geriatric behavioural changes that are not caused by other medical problems, although the two may not be mutually exclusive. Therefore, the practitioner must rely heavily on owner reports and history to ensure prompt diagnosis and treatment. The absence of any approved dietary or pharmaceutical interventions for cognitive dysfunction adds a further challenge, although several possibilities exist.
Evidence base:
This article draws on recent research that has produced neuropathological, cognitive and behavioural evidence for cognitive dysfunction in aging cats. As an impetus to further our understanding of this disease and potential treatment options, the authors propose a behavioural checklist that might aid in the clinical diagnosis of feline CDS and discuss treatment options that have proven successful in the canine counterpart of this disease.
Apolipoprotein E4 (ApoE4) is a risk factor for Alzheimer's disease (AD). Whether this risk arises from a deficient function of E4 or the lack of protection provided by E2 or E3 is unclear. Previous studies demonstrate that deprivation of folate and vitamin E, coupled with dietary iron as a pro-oxidant, for 1 month displayed increased presenilin 1 (PS-1) expression, gamma-secretase, and Abeta generation in mice lacking ApoE (ApoE-/- mice). While ApoE-/- mice are a model for ApoE deficiency, they may not reflect the entire range of consequences of E4 expression. We therefore compared herein the impact of the above deficient diet on mice expressing human E2, E3, or E4. As folate deficiency is accompanied by a decrease in the major methyl donor, S-adenosyl methionine (SAM), additional mice received the deficient diet plus SAM. E2 was more protective than murine ApoE or E3 and E4. Surprisingly, PS-1 and gamma-secretase were over-expressed in E3 to the same extent as in E4 even under a complete diet, and were not alleviated by SAM supplementation. Abeta increased only in E4 mice maintained under the complete diet, and was alleviated by SAM supplementation. These findings suggest dietary compromise can potentiate latent risk factors for AD.
Aged dogs (beagles) develop losses in executive function, learning and memory. The severity of decline in these cognitive domains represents a spectrum that captures normal aging, mild cognitive impairment and early/mild Alzheimer's disease (AD) in humans. In parallel, dogs naturally accumulate several types of neuropathology (although not all) consistent with human brain aging and AD including cortical atrophy, neuron loss, loss of neurogenesis, amyloid-beta (Abeta) plaques, cerebral amyloid angiopathy and oxidative damage. Many of these neuropathological features correlate with the extent of cognitive decline in a brain region-dependent manner. Dogs are ideally suited for longitudinal studies, and we provide a summary of the beneficial effects of an antioxidant diet, behavioral enrichment, and Abeta immunotherapy. In addition, combinatorial treatment approaches can be a powerful strategy for improving brain function through enhancement of multiple molecular pathways.
Old, middle-aged, and young dogs were compared on discrimination and reversal learning and on acquisition of a delayed-nonmatching-to-sample (DNMS) test of recognition memory. DNMS acquisition was acquired more rapidly by young dogs. Reversal deficits were found between aged mixed-breed dogs and young beagles, but not between old and young beagles. Aged beagles also showed unexpected deficits in reward approach and object approach learning. Aged mixed-breed dogs did not show deficits in reward approach and object approach learning, but they learned the discrimination task more slowly than the age-matched beagles. A detailed analysis of response patterns indicated that once present, the development of side preferences contributed to deficits of old dogs in discrimination learning. In the discrimination reversal, old dogs were more persistent in responding to the previously rewarded stimulus object. Findings suggest that the dog, like other species, shows age-dependent deterioration in cognitive function, the extent of deterioration is a function of both task and previous experience, and at least part of the deterioration is a result of increased behavioral rigidity. Results also indicate that it is important to control for breed differences and previous experience.