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Background Total physical activity is positively associated with brain volume and cognition in older adults. While we have ample evidence that recreational physical activity influences brain health, the contributions of other daily activities are less understood. In particular, the associations between household physical activity and brain health in older adults is underexplored. The purpose of this study was to identify associations between household physical activity, brain volume, and cognition in a sample of cognitively unimpaired older adults. Methods We report data from 66 cognitively unimpaired older adults (71 ± 4 years) who participated in a health evaluation, cognitive assessment, and structural brain imaging. Physical activity was assessed using the Phone-FITT questionnaire and separated into household and recreational physical activity. We quantified whole brain volume, gray matter volume, and white matter volume, and assessed cognitive performance in four domains: memory, working memory/attention, processing speed, and executive function. Associations between physical activity, brain volume, and cognition were investigated in an omnibus approach using two multivariate analysis of variance (MANOVA) models. The first model assessed the associations between physical activity and brain volume adjusting for age, sex, Framingham Risk score (FRS) and intracranial volume. The second model assessed the associations between physical activity and overall cognitive performance adjusting for age, sex, FRS and education. Post hoc regression analyses were conducted to investigate significant MANOVA results. We also conducted further regression analyses to investigate associations with hippocampal and frontal lobe volume. Results Household, but not recreational, physical activity was positively associated with brain volume measurements (F = 3.07, p = .035), specifically gray matter volume (t = 2.51, p = .015). Further exploratory analyses identified that household physical activity was associated with hippocampal (p = .015) and frontal lobe (p = .010) volume. No significant relationships were observed between household or recreational physical activity and cognition. Conclusion Time spent engaging in household physical activity was positively associated with brain volume, specifically gray matter volume, in older adults. Highlighting the benefits associated with household chores may motivate older adults to be more active by providing a more attainable, low risk form of physical activity.

Objectives This study examined the effect of dietary patterns and engagement in cognitive stimulating lifestyle (CSL) behaviors on the trajectory of global cognition, executive function (EF), and verbal episodic memory (VEM). Methods Western and prudent dietary patterns were empirically derived using food frequency questionnaire responses from 350 community-dwelling older adults (mean age: 73.7 years) participating in the Quebec Longitudinal Study on Nutrition and Successful Aging. CSL was represented by a binary composite indicator based on education, occupational complexity, and social engagement. Global cognition, EF, and VEM were assessed prospectively. Results Primary effect models revealed an association between higher Western dietary pattern score and a greater rate of decline in global cognition and EF. Higher Western dietary pattern adherence was also associated with poorer baseline VEM. Primary effect models also revealed that CSL was independently associated with baseline global cognition and EF. Effect modification models suggested an interactive effect between Western dietary pattern and CLS on global cognition only. No associations were found for prudent dietary pattern score. Discussion Contributing to existing research supporting the negative impact of consuming an unhealthy diet on cognitive function, the current study suggests increased vulnerability among older adults who do not engage in a CSL. These findings can inform the development of lifestyle intervention programs that target brain health in later adulthood.

Peripheral biomarkers have shown significant value in predicting brain health and may serve as a useful proxy measurement in the assessment of evidence-based lifestyle behavior modification programs, including physical activity and nutrition programs, that aim to maintain cognitive function in late life. The aim of this systematic review was to elucidate which peripheral biomarkers are robustly associated with cognitive function among relatively healthy non-demented older adults. Following the standards for systematic reviews (PICO, PRIMSA), and employing MEDLINE and Scopus search engines, 222 articles were included in the review. Based on the review of biomarker proxies of cognitive health, it is recommended that a comprehensive biomarker panel, or biomarker signature, be developed as a clinical end point for behavior modification trials aimed at enhancing cognitive function in late life. The biomarker signature should take a multisystemic approach, including lipid, immune/inflammatory, and metabolic biomarkers in the biological signature index of cognitive health.

Background: Healthy diet and exercise are associated with reduced risk of dementia in older adults. Evidence for the impact of clinical trials on brain health is less consistent, especially with dietary interventions which often rely on varying intervention approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counselling approach among older adults with vascular risk factors (VRFs) and early dementia risk. Methods: Participants with VRF’s and SCD or early MCI were cluster randomized into the intervention (exercise + Baycrest Brain-healthy Eating Approach (EX+DIET)) or control group (exercise + brain health education (EX+ED)). Both groups participated in 1-hour of supervised exercise per week and were prescribed additional exercise at home. EX+DIET involved 1-hour per week of group-based dietary counselling comprising didactic education focused on brain healthy eating recommendations, goal setting and strategy training. Whereas, EX+ED involved 1-hour per week of group-based brain health education. The primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included fitness, diet, cognition, and blood biomarkers. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. Results: Of 190 older adults contacted, 14 (7%) were eligible and randomized, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and diet/education sessions on average. All 6-month follow-up assessments pre-COVID-19 were completed but disruptions to testing during the pandemic resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the intervention. Mean improvements in peak oxygen consumption were observed in both EX+DIET (d = .98) and EX+ED (d =1.15) groups. Substantial improvements in diet and HbA1c were observed in the EX+DIET group compared to EX+ED (d = 1.75 and 1.07, respectively). Conclusions: High adherence and retention rates were observed among LEAD participants and preliminary findings illustrate improvements in cardiorespiratory fitness and diet quality. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. Trial Registration: ClinicalTrials.gov identifier: NCT03056508

Background Consumption of a prudent dietary pattern rich in healthy nutrients is associated with enhanced cognitive performance in older adulthood, while a Western dietary pattern low in healthy nutrients is associated with poor age-related cognitive function. Sex differences exist in dietary intake among older adults; however, there is a paucity of research examining the relationship between sex-specific dietary patterns and cognitive function in later life. Methods The current study aimed to investigate sex differences in the relationship between sex-specific dietary pattern adherence and global cognitive function at baseline and over a 3-year follow-up in 1268 community-dwelling older adults (Mage = 74 years, n = 664 women, n = 612 men) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). A 78-item Food Frequency Questionnaire was used to estimate dietary intake over the previous year. Sex-specific dietary pattern scores were derived using principal component analysis. Global cognition was assessed using the Modified Mini-Mental State Examination (3MS). Results Adjusted linear mixed effects models indicated that a healthy, prudent dietary pattern was not associated with baseline cognitive performance in men or women. No relationship was found between Western dietary pattern adherence and baseline cognitive function in women. Among men, adherence to an unhealthy, Western dietary pattern was associated with poorer baseline cognitive function (β = − 0.652, p = 0.02, 95% CI [− 1.22, − 0.65]). No association was found between prudent or Western dietary patterns and cognitive change over time in men or women. Conclusions These findings highlight the importance of conducting sex-based analyses in aging research and suggest that the relationship between dietary pattern adherence and cognitive function in late life may be sex-dependent.

Purpose White matter hyperintensities (WMH) are prevalent among older adults and are often associated with cognitive decline and increased risk of stroke and dementia. Vascular risk factors (VRFs) are linked to WMH, yet the impact of multiple VRFs on gray matter function is still unclear. The goal of this study was to test for associations between the number of VRFs and cerebrovascular reactivity (CVR) and resting state (RS) coactivation among individuals with WMH. Materials and Methods Twenty-nine participants with suspected WMH were grouped based on the number of VRFs (subgroups: 0, 1, or ≥2). CVR and RS coactivation were measured with blood oxygenation level-dependent (BOLD) imaging on a 3T magnetic resonance imaging (MRI) system during hypercapnia and rest, respectively. Default-mode (DMN), sensory-motor, and medial-visual networks, generated using independent component analysis of RS-BOLD, were selected as networks of interest (NOIs). CVR-BOLD was analyzed using two methods: 1) a model-based approach using CO2 traces, and 2) a dual-regression (DR) approach using NOIs as spatial inputs. Average CVR and RS coactivations within NOIs were compared between VRF subgroups. A secondary analysis investigated the correlation between CVR and RS coactivation. Results VRF subgroup differences were detected using DR-based CVR in the DMN (F20,2 = 5.17, P = 0.015) but not the model-based CVR nor RS coactivation. DR-based CVR was correlated with RS coactivation in the DMN (r2 = 0.28, P = 0.006) but not the sensory-motor nor medial-visual NOIs. Conclusion In individuals with WMH, CVR in the DMN was inversely associated with the number of VRFs and correlated with RS coactivation. J. Magn. Reson. Imaging 2015;42:1369–1376.

According to the Alzheimer Society of Canada, within the next generation, Canada will experience a more than doubling of individuals living with dementia and a potentially economically crippling 10-fold increase in costs to Canadians. Up to 50% of cases with dementia can be attributed to seven modifiable, predominantly vascular and/or lifestyle-associated, risk factors. Multi-modal dementia risk reduction strategies, targeting diet, exercise, mental stimulation, and vascular risk monitoring, are likely to be the most successful. Diet-related strategies need to focus on overall diet quality and not on individual foods or nutrients. High-quality diets that are associated with better cognitive function and lower dementia risk with aging are high in vegetables, fruits, nuts, whole grains, and fish and low in red meat, high-fat dairy products, sweets, and highly processed foods. It is the time to embed risk reduction strategies into our public health and healthcare infrastructure to proactively address the challenges posed by population aging.

In a prospective study of environmental factors affecting cognitive recovery from stroke, adult male rats were reared for 3 months in a high-risk (relatively isolated, low activity, high-fat diet, high-stress) or low-risk (social, healthy diet, low-stress, physically active) environment. They then received cognitive testing to assess various aspects of learning and memory before undergoing 2-vessel occlusion (2VO) of the carotid arteries, or sham surgery. Rats were returned to their respective environments post-operatively. Relative to pre-operative levels, 2VO rats exhibited significant cognitive losses that were consistently greater in the high-risk group than its low-risk counterpart. As well, the high-risk 2VO group was impaired, relative to the low-risk 2VO group on tests of new learning introduced post-operatively. At 3-month follow-up testing, rats that had undergone 2VO surgery exhibited further decline on some tests but recovery on others, with recovery generally slower in the high-risk 2VO group. The high-risk environment also affected rats' pre-operative cognitive performance and, to a lesser extent, their performance following sham surgery. Overall, the study shows that rats experiencing cerebral ischemia are more likely to experience severe cognitive deficits if exposed to a high-risk environment and recover more slowly than ischemic rats in a more favorable environment. The results underscore the importance of lifestyle factors with respect to the impact of stroke on cognition and in assessing prospects for recovery of function.

Canada is experiencing a rise in type II diabetes mellitus (T2DM), a known risk factor for accelerated cognitive decline and dementia. Within the context of an aging population, this will impose significant individual and societal burden, making the development of prevention programs imperative.This pilot study examines the effects of the Diabetes Exercise and Healthy Lifestyle Service, a 24-week intervention program, on cardiovascular, metabolic regulation and cognitive function in adults with T2DM.Seventeen middle-aged participants provided blood samples for biological markers, underwent cognitive testing and a physical stress test pre- and post-intervention. Cognitive performance was evaluated using the California Verbal Learning Test (CVLT), Digit Symbol Substitution Tasl (DSST) and fluency test.Adjusted models reveal participants displayed increased cardiovascular fitness (VO2 peak: Mchange=4.09 mL∙kg∙min(-1) SE=1.4), peak heart rate (Mchange= 9.28 beats⋅min(-1) SE=2.68) and change in heart rate (Mchange=10.71 SE=1.76) in response to the stress test (ps0.05) following the 24-week intervention. A decrease in body mass index (BMI) (Mchange= -1.03 SE=0.40) and depressive symptomatology (CES-D: Mchange = -3.62 SE=1.44) was also found (ps0.05). No change was found for lipid and glucose levels. Surprisingly, analyses showed that cognitive performance on the CVLT immediate recall (M= -4.37 SE=2.21), CVTL short-delay recall (M= -1.06 SE=0.55), DSST (Mchange= -3 SE=0.53) and category fluency (Mchange= -1.69 SE=0.78) declined following the intervention (ps0.05); however, decline on the CVLT was limited to adults with co-morbid T2DM and hypertension.Additional research is needed to evaluate the benefit of an exercise and lifestyle program that targets cognitive health in those with T2DM.

Objectives To determine how cardiovascular risk is associated with working memory task performance and task-related suppression of default-mode network (DMN) activity in cognitively intact older adults. Design A cross-sectional functional magnetic resonance imaging study of older adults with cardiovascular risk factors. Setting Rotman Research Institute, Baycrest Health Sciences. Participants Thirty older adults with cardiovascular risk factors. Measurements Participants provided health information and a blood sample, and underwent functional magnetic resonance imaging during a working memory task and during a breath-hold task to assess cerebrovascular reactivity. Results Higher plasma low-density lipoprotein cholesterol (LDL-C) was associated with poorer working memory task performance (P = 0.008) and reduced task-related DMN suppression (P = 0.005). A composite index of cardiovascular risk, the Framingham General Cardiovascular Risk Profile, showed no associations with task performance or task-related DMN suppression. These findings were independent of white matter burden and cerebrovascular reactivity and thus cannot be accounted for by individual differences in neurovascular health. Conclusion These findings suggest a deleterious effect of elevated LDL-C on working memory task performance and task-related DMN suppression in older adults with cardiovascular risk. The relations between the Framingham General Cardiovascular Risk Profile, cognitive task performance, and DMN function require further study.

Assessment of long-term phylloquinone exposure is challenging in studies investigating vitamin K in health. Data are equivocal as to whether a single measurement of circulating phylloquinone would be adequate. The primary purpose of the present study was to validate the use of a single measurement of serum phylloquinone as a surrogate for long-term phylloquinone exposure in healthy older adults. Using data from the Quebec Longitudinal Study on Nutrition and Successful Aging, the objectives were to: 1) determine the reproducibility of circulating phylloquinone over 2 y (n = 234); 2) calculate how a single measurement would rank or classify individuals and attenuate the regression coefficient between circulating phylloquinone and a health outcome; and 3) investigate the association of a single measurement of serum phylloquinone with long-term phylloquinone intakes assessed over the year prior to the blood draw (n = 228). The variance analysis based on 2 blood samples showed a fair to good reproducibility for serum phylloquinone (intra-class correlation = 0.49). The correlation coefficient between the ranking of individuals based on a single measurement of circulating phylloquinone and the "true" ranking would be 0.70. The multiple regression analysis showed that long-term phylloquinone intake was the strongest predictor of serum phylloquinone (t = 4.94; P < 0.001). The partial correlation coefficient (r = 0.32) was comparable with those reported in studies where blood sampling and diet recording were juxtaposed and/or multiple blood samples were used. The present study provides evidence that the use of a single measurement of circulating phylloquinone is adequate for assessing long-term phylloquinone exposure in healthy older adults.

Rationale Glucose enhancing effects in older adults have mostly been observed for episodic memory, but have recently been found for attentional control performance. Yet, brain activation patterns underlying these effects are still unknown. Objective The present study examined the acute effects of glucose ingestion on prefrontal brain activation during the execution of a divided attention task in fasting non-diabetic older adults. Methods Twenty older adults (60 years and older) took part in the study that included two experimental sessions. After an overnight fast, participants received either a glucose drink (50 g) or a placebo (saccharin) drink, following which they completed a dual-task. During task execution, prefrontal activation was recorded with functional near-infrared spectroscopy (fNIRS). A repeated-measures design was used such that each participant served as his or her own control. The two experimental sessions were counterbalanced among participants and were performed two weeks apart. Results When participants were in the glucose condition, they showed similar dual-task costs for both tasks, whereas in the placebo condition they prioritized one task over the other, with a significantly larger dual-task cost for the non-prioritized task (p

Less efficient glucose regulation, the ability to metabolize glucose, has been associated with poorer cognitive performances in older individuals not meeting criteria for type 2 diabetes ( Messier, Tsiakas, Gagnon,Desrochers, 2010 ). Yet, the influence of glucose regulation on attentional functions, which are sensitive to aging, is still unclear. The present study examined the relationship between glucose regulation and performances on attentional tasks in nondiabetic older adults. Twenty-two participants (60 years and older) were tested on neuropsychological tests of attention (Trail Making test, modified Stroop test) and on a computerized dual task, after receiving a 50-g glucose drink. Participants with the worse glucose regulation committed more errors on the switching condition of the modified Stroop test (p.05) and tended to make more errors in divided-attention trials of the computerized dual task (p = .05). Altogether, these results suggest that glucose regulation may transiently influence performances of metabolically healthy older adults on tasks requiring switching attention.

The association between obesity, other cardiovascular risk factors, and cognitive function in a Canadian First Nations population was investigated using a cross-sectional design. Eligible individuals were aged >/=18 years, without a history of stroke, nonpregnant, with First Nations status, and who had undergone cognitive function assessment by the Clock Drawing Test (CDT) and Trail Making Test Parts A and B. Parts A and B were combined into an Executive Function Score (TMT-exec). Hypertension, a previous history of cardiovascular disease, dyslipidemia, metabolic syndrome, insulin resistance, and the presence and duration of diabetes were examined in addition to obesity. In the case of TMT-exec only, obese individuals were at an approximately fourfold increased risk for lowered cognitive performance compared to those who were not obese in multivariable models (odds ratio (OR): 3.77, 95% confidence interval (CI): 1.46-9.72) whereas there was no effect for overweight individuals compared to those with a normal weight in unadjusted analysis. Those having an increased waist circumference also had 5 times the risk compared to those without an increased waist circumference (OR: 5.41, 95% CI: 1.83-15.99). Adjusted for age, sex, and insulin resistance, individuals having the metabolic syndrome were at an approximately fourfold increased risk compared to those without the metabolic syndrome (OR: 3.67, 95% CI: 1.34-10.07). No other cardiovascular risk factors were associated. Obesity and metabolic syndrome were associated with lowered cognitive performance. These results highlight the importance of studying the health effects of obesity beyond traditional disease endpoints, even in a relatively youthful population.

Background: We investigated the associations among cardiovascular risk factors, carotid atherosclerosis and cognitive function in a Canadian First Nations population. Methods: Individuals aged ≥18 years, without stroke, nonpreg- nant and with First Nations status were assessed by the Trail Making Test Parts A and B. Results were combined into a Trail Making Test executive function score (TMT-exec). Doppler ultrasonography assessed carotid stenosis and plaque volume. Anthropometric, vascular and metabolic risk factors were assessed by interview, clinical examinations and blood tests. Results: For 190 individuals with TMT-exec scores, the median age of the population was 39 years. Compared to the reference group, individuals with elevated levels of left carotid stenosis (LCS) and total carotid stenosis (TCS) were less likely to demonstrate lowered cognitive performance [LCS, odds ratio (OR): 0.47, 95% confidence interval (CI): 0.24–0.96; TCS, OR: 0.40, 95% CI: 0.20–0.80]. No effect was shown for plaque volume. In structural equation modeling, we found that for every 1-unit change in the anthropometric factor in kg/m2, there was a 0.86-fold decrease in the percent of TCS (p < 0.05). Conclusions: Individuals with elevated levels of LCS and TCS were less likely to demonstrate lowered performance. There was some suggestion that TCS mediates the effect of anthropometric risk factors on cognitive function.

Weight loss is a common problem among both community-dwelling and institutionalized older adults with Alzheimer disease (AD) and is associated with mortality, morbidity, disease progression, and poor quality of life. The causes of weight loss in this population are multifaceted and include loss of appetite secondary to deterioration of brain regions associated with feeding behavior and functional and behavioral problems associated with AD that make it difficult for individuals to consume adequate energy. The most common weight management strategy is to provide high-energy nutritional supplements to individuals at risk of weight loss. Supplementation is generally effective but tends to be least beneficial for those with the lowest body mass indices. Environmental and social interventions related to mealtimes and feeding are also important.

Inflammatory markers predict memory dysfunction in elderly patients, but their contribution to memory deficits in adults with Type 2 diabetes mellitus (T2DM) is less well understood. The present study determined whether specific single-nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-alpha) predict verbal memory in older patients with T2DM. Immediate and delayed verbal memory were assessed using word list and paragraph recall tests in a cohort of subjects with T2DM during 2 sessions, separated by 48 weeks. The presence of the TNF-alpha-238A allele, which has been shown to decrease gene expression, consistently predicted better baseline performance and protected against memory decline over a period of 48 weeks. Therefore, inflammatory mediators may be important modulators of memory function in individuals with T2DM.

OBJECTIVES: To determine whether increases in caloric intake associated with consumption of a mid-morning nutritional supplement for 3 weeks were maintained in the week after stopping the supplement and to investigate the effects of body mass index (BMI) and cognitive and behavioral measures on this response. DESIGN: Secondary analysis of a previously published randomized, crossover, nonblinded clinical trial. SETTING: A fully accredited geriatric care facility affiliated with the University of Toronto. PARTICIPANTS: Thirty institutionalized seniors with probable Alzheimer's disease (AD) who ate independently. MEASUREMENTS: Investigator-weighed food intake, body weight, cognitive (Severe Impairment Battery; Global Deterioration Scale) and behavioral (Neuropsychiatric Inventory—Nursing Home version; London Psychogeriatric Rating Scale) assessments. RESULTS: Individuals who responded successfully to supplementation as indicated by increases in daily energy intake were likely to maintain 58.8% of that increase postsupplementation, although stopping the supplement was associated with decreased habitual energy intake in low-BMI individuals who reduced their daily intakes during supplementation in response to the extra calories. Cognitive/behavioral tests were not reliable predictors of postsupplement intake. CONCLUSION: Institutionalized seniors with probable AD are likely to alter their usual energy intakes to maintain changes resulting from 3 weeks of supplementation. This effect may allow for rotating supplementation schedules in nursing homes that could reduce staff burden, but only for those individuals who are most likely to respond favorably. These data indicate that nutritional supplements and diet plans should be carefully prescribed in low-BMI individuals to limit variability in total energy provided and thus prevent lower-than-normal intake.

Transient hyperglycaemia, consistent with that observed with normal meal ingestion, may be detrimental to cognitive performance in adults with type 2 diabetes. This study determined whether minimising the postprandial increase in blood glucose through the ingestion of low- rather than high-glycaemic-index (GI) carbohydrate meals differentially affected cognitive performance in the postprandial period.Using a within-individual design, 21 free-living subjects (65+/-7.29 years) with type 2 diabetes consumed 50 g carbohydrate as a meal with either a low GI (pasta) or a high GI (white bread), or water on three separate mornings following an overnight fast. Neuropsychological tests were administered and plasma glucose concentrations measured.Higher postprandial blood glucose AUC (gAUC) was associated with poorer verbal memory (paragraph recall, p=0.01; word list recall, p=0.012). Both the GI of the carbohydrate meal and individual differences in response to meal ingestion contributed to the variation in gAUC and consequent memory recall. Bread consumption, relative to pasta, resulted in both a higher gAUC (p0.05) and worse delayed verbal memory performance (paragraph recall, p=0.042; wordlist recall, p=0.035). Additionally, performance following bread consumption was poorer than that following pasta on measures of working memory, executive function and auditory selective attention, while sustained attention showed no sensitivity to type of carbohydrate food consumed.Consuming 50 g of a low-GI carbohydrate meal, relative to a high-GI carbohydrate meal, generally results in better cognitive performance in the postprandial period in adults with type 2 diabetes, particularly in those individuals who experience the greatest food-induced elevations in blood glucose levels.

This research summarises a research program that is concerned with the effects of high fat diets on cognitive function in rats. The diets selected accurately represent current upper limits of human fat consumption in western societies. Rats fed with diets high in saturated or unsaturated fat for 3 months, were severely impaired on a range of learning and memory tasks. Related studies showed that these effects were modulated by concentration of fat, environmental influences, and treatment with glucose. More work is needed to identify the neurobiological mechanisms underlying this impairment but saturated fatty acid intake, as well as insulin resistance and glucose intolerance may be important factors. In demonstrating a clear relationship between obesity and cognitive impairment, this research has important implications for aging. Older adults are particularly vulnerable to the adverse effects of dietary fat and the present results underscore the importance of evidence that seniors with marginal levels of nutrient intake often perform poorly on tests of cognitive function, and are at increased risk for various forms of dementia.

Results from our work in rats and others findings from human epidemiologic studies demonstrate deficits in cognitive performance following chronic ingestion of high fat, high saturated fat, diets. Yet, the precise physiologic mechanism underlying these deficits is not well understood. We report that older adults with insulin resistance show remarkably similar deficits in cognitive function and respond to glucose ingestion in a comparable manner to rodents fed a high-fat diet, suggesting that insulin resistance is a probable mediator of these diet-induced deficits. As insulin resistance worsens to overt type 2 diabetes, profound deficits in cognitive functions, especially those dependent on the medial temporal lobes, are apparent in both obese Zucker rats and humans with type 2 diabetes. Unlike the older adult with insulin resistance, glucose ingestion further impairs medial temporal lobe function in adults with type 2 diabetes. Collectively, the human and rodent data point to a role of diet-induced endocrine abnormalities, including the development of insulin resistance, as mediating the cognitive deficits associated with high fat consumption.

Objectives: To examine whether providing a midmorning nutrition supplement increases habitual energy intake in seniors with probable Alzheimer's disease (AD) and to investigate the effects of body weight status and cognitive and behavioral function on the response to the intervention. Design: Randomized, crossover, nonblinded clinical trial. Setting: A fully accredited geriatric teaching facility affiliated with the University of Toronto's Medical School with a home for the aged. Participants: Thirty-four institutionalized seniors with probable AD who ate independently. Intervention: Nutrition supplements were provided between breakfast and lunch for 21 consecutive days and compared with 21 consecutive days of habitual intake. Measurements: Investigator-weighed food intake, body weight, cognitive function (Severe Impairment Battery and Global Deterioration Scale), behavioral disturbances (Neuropsychiatric Inventory—Nursing Home Version), and behavioral function (London Psychogeriatric Rating Scale). Results: Relative to habitual intake, group mean analyses showed increased 24-hour energy, protein, and carbohydrate intake during the supplement phase, but five of 31 subjects who finished all study phases completely compensated for the energy provided by the supplement by reducing lunch intake, and 24-hour energy intake was enhanced in only 21 of 31 subjects. Compensation at lunch was more likely in subjects with lower body mass indices, increased aberrant motor behavior, poorer attention, and increased mental disorganization/confusion. Conclusion: Nutrition supplements were least likely to enhance habitual energy intake in subjects who would normally be targeted for nutrition intervention—those with low body weight status. Those likely to benefit include those with higher body mass indices, less aberrant motor problems, less mental disorganization, and increased attention.

OBJECTIVES: To provide practitioners with benchmarks for micronutrient supplementation policies for older residents of long-term care (LTC) facilities, based upon residents' usual energy intake. DESIGN: Retrospective secondary analysis of nutrient intake and delivery data, obtained from 21 consecutive collection days. SETTING: A fully accredited geriatric teaching facility, affiliated with the University of Toronto's Medical School, that includes a chronic care hospital and a home for the aged, housing more than 800 senior residents. PARTICIPANTS: Twenty-three cognitively impaired residents who retained the ability to feed themselves. MEASUREMENTS: Average daily micronutrient (vitamin and mineral) content of two common diet types—unrestricted diet as tolerated and lactose-free—were evaluated based upon all foods served during a 28-day cycle of menus, providing an estimate of total possible micronutrient intake. Energy intake needed to meet recommended intakes for each of the micronutrients was then determined and compared with actual dietary intakes. RESULTS: Even if entirely consumed, neither diet (providing approximately 2,000 kcal/d) supplied sufficient quantities of vitamins (vitamin E, pantothenic acid) and minerals (calcium, zinc, copper and manganese) to enable residents to meet recommended intakes, making these deficiencies iatrogenic in nature. As projected intake levels fell to reflect ranges more consistently observed in LTC residents (1,000–1,500 kcal/d), the number and severity of risk nutrients increased. Similar predictions, based upon actual intake measurements, were made and confirmed. CONCLUSIONS: The traditional approach of developing LTC menus using resources such as Canada's Food Guide or the Food Guide Pyramid of the United States results in iatrogenic malnutrition. New guidelines are needed that are targeted toward the special needs of older adults who have low food intakes. In the interim, all older LTC residents require full-spectrum vitamin and mineral supplements.

White matter hyperintensities (WMH) are prevalent among older adults and are often associated with cognitive decline and increased risk of stroke and dementia. Vascular risk factors (VRFs) are linked to WMH, yet the impact of multiple VRFs on gray matter function is still unclear. The goal of this study was to test for associations between the number of VRFs and cerebrovascular reactivity (CVR) and resting state (RS) coactivation among individuals with WMH.Twenty-nine participants with suspected WMH were grouped based on the number of VRFs (subgroups: 0, 1, or ≥2). CVR and RS coactivation were measured with blood oxygenation level-dependent (BOLD) imaging on a 3T magnetic resonance imaging (MRI) system during hypercapnia and rest, respectively. Default-mode (DMN), sensory-motor, and medial-visual networks, generated using independent component analysis of RS-BOLD, were selected as networks of interest (NOIs). CVR-BOLD was analyzed using two methods: 1) a model-based approach using CO2 traces, and 2) a dual-regression (DR) approach using NOIs as spatial inputs. Average CVR and RS coactivations within NOIs were compared between VRF subgroups. A secondary analysis investigated the correlation between CVR and RS coactivation.VRF subgroup differences were detected using DR-based CVR in the DMN (F20,2 = 5.17, P = 0.015) but not the model-based CVR nor RS coactivation. DR-based CVR was correlated with RS coactivation in the DMN (r(2) = 0.28, P = 0.006) but not the sensory-motor nor medial-visual NOIs.In individuals with WMH, CVR in the DMN was inversely associated with the number of VRFs and correlated with RS coactivation.

OBJECTIVE To review the effect of vitamin D on bone density and fractures in postmenopausal women. DATA SOURCE We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data. STUDY SELECTION We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr. DATA EXTRACTION For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 microg yield larger effects than lower doses. Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88), an effect that was similar in trials of standard and hydroxylated vitamin D. CONCLUSIONS Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures. The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.

The rising prevalence of type 2 diabetes (T2DM) and hypertension in older adults, and the deleterious effect of these conditions on cerebrovascular and brain health, is creating a growing discrepancy between the "typical" cognitive aging trajectory and a "healthy" cognitive aging trajectory. These changing health demographics make T2DM and hypertension important topics of study in their own right, and warrant attention from the perspective of cognitive aging neuroimaging research. Specifically, interpretation of individual or group differences in blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) or positron emission tomography (PET H2O15) signals as reflective of differences in neural activation underlying a cognitive operation of interest requires assumptions of intact vascular health amongst the study participants. Without adequate screening, inclusion of individuals with T2DM or hypertension in "healthy" samples may introduce unwanted variability and bias to brain and/or cognitive measures, and increase potential for error. We conducted a systematic review of the cognitive aging neuroimaging literature to document the extent to which researchers account for these conditions. Of the 232 studies selected for review, few explicitly excluded individuals with T2DM (9%) or hypertension (13%). A large portion had exclusion criteria that made it difficult to determine whether T2DM or hypertension were excluded (44% and 37%), and many did not mention any selection criteria related to T2DM or hypertension (34% and 22%). Of all the surveyed studies, only 29% acknowledged or addressed the potential influence of intersubject vascular variability on the measured BOLD or PET signals. To reinforce the notion that individuals with T2DM and hypertension should not be overlooked as a potential source of bias, we also provide an overview of metabolic and vascular changes associated with T2DM and hypertension, as they relate to cerebrovascular and brain health.

Objective Type 2 diabetes mellitus is characterized by metabolic dysregulation in the form of hyperglycemia and insulin resistance and can have a profound impact on brain structure and vasculature. The primary aim of this study was to identify brain regions where the combined effects of type 2 diabetes and hypertension on brain health exceed those of hypertension alone. A secondary objective was to test whether vascular impairment and structural brain measures in this population are associated with cognitive function. Research design and methods We enrolled 18 diabetic participants with hypertension (HTN + T2DM, 7 women, 71.8 ± 5.6 years) and 22 participants with hypertension only (HTN, 12 women, 73.4 ± 6.2 years). Cerebrovascular reactivity (CVR) was assessed using blood oxygenation level dependent (BOLD) MRI during successive breath holds. Gray matter structure was evaluated using cortical thickness (CThk) measures estimated from T1-weighted images. Analyses of cognitive and blood data were also performed. Results Compared to HTN, HTN + T2DM had decreased CVR and CThk in a spatially overlapping region of the right occipital lobe (P 0.05), CThk in the right lingual gyrus ROI and regions resulting from a vertex-wise analysis (including posterior cingulate, precuneus, superior and middle frontal, and middle and inferior temporal regions (P, Highlights • CThk and CVR decrease in the presence of T2DM and HTN vs. HTN alone. • Combined effects of T2DM and HTN are prominent in the right occipital areas. • CVR impairment in HTN + T2DM extends to bilateral occipito-parietal areas. • Executive function correlates with CThk but not CVR in this cohort.

Individuals with Alzheimer's disease (AD) are highly susceptible to weight loss and malnutrition, which, to date, have not been associated with decreased food consumption. The current study examined food intake patterns and how they change in relation to body mass index (BMI), behavioral function, and cognitive status in institutionalized seniors with AD.Twenty-one consecutive days of investigator-weighed food intake collections were conducted on 25 subjects with likely AD residing at a home for the aged. All subjects maintained the ability to self-feed.Eighty-eight percent of participants did not meet targeted energy needs, including an estimated 37% prevalence of protein inadequacy. Subjects with increased behavioral difficulties, based on the London Psychogeriatric Rating Scale, had reduced meal-related intakes that were highly associated with decreased energy consumption at dinner. With behavioral changes, particularly increased mental disorganization and confusion, there was a shift in circadian eating patterns such that the greatest proportion of daily energy was consumed at breakfast. Individuals with low BMIs tended to be those with more behavioral difficulties, such that BMI was also associated with the shift in overall eating patterns.Changes in behavioral function in seniors with AD result in a circadian shift in intake patterns with the preponderance of calories consumed at breakfast in those with increased behavioral difficulties. This shift in eating patterns associates both with poor overall intake and poor BMI.

Background. Alterations in circadian rhythms and behavioral difficulties likely impact meal consumption patterns in elderly individuals with probable Alzheimer’s disease (AD). Despite these known changes, the profile of meals provided in the institution parallels the needs of younger, free-living, healthy populations. This investigation examined the impact of food delivery patterns on achieved intakes in elderly individuals with probable AD in a long-term care facility and how this relationship changes depending on time of day, body weight status, behavioral function, and cognitive ability. Methods. Twenty-one consecutive days of investigator-weighed food intake and delivery collections were conducted on 25 elderly individuals with probable AD who maintained the ability to self-feed. Results. Energy consumed was positively associated with energy delivered for the majority of subjects, although the strength of this relationship varied across subjects and throughout the day. Energy delivered had the greatest impact on energy consumed at breakfast and the least impact at dinner in those with the greatest behavioral difficulties and cognitive impairment. Although those with low body mass indexes (BMIs) were likely to be delivered more energy, the impact of delivery on intakes decreased as energy delivered increased. Conclusions. Delivering excess energy to patients with poor BMIs likely does not result in increased energy consumption. Behavioral and cognitive deterioration leads to a shift in the time of day that energy delivered has an impact on energy consumption, with the most progressed individuals being most impacted by foods delivered in the morning, suggesting that traditional meal practices are inappropriate for elderly individuals with AD.

A glucose drink has been shown to improve memory in persons with poor glucose regulation and poor cognition.The objective of this study was to determine 1) whether an association between cognition and glucose regulation is apparent in healthy seniors and 2) the effects of dietary carbohydrates on cognition.After an overnight fast, 10 men and 10 women (aged 60-82 y) consumed 50 g carbohydrate as glucose, potatoes, or barley or a placebo on 4 separate mornings. Cognitive tests were administered 15, 60, and 105 min after ingestion of the carbohydrate. Plasma glucose and serum insulin were measured.In a multiple regression analysis, poor baseline (placebo) verbal declarative memory (immediate and 20-min delayed paragraph recall and word list recall) and visuomotor task performance were predicted by poor beta cell function, high incremental area under the glucose curve, low insulin resistance, and low body mass index. The difference in plasma glucose after food consumption [glucosepotatoesbarleyplacebo (P:0.03)] did not predict performance. Although overall performance did not differ with consumption of the different test foods, baseline score and beta cell function correlated with improvements in immediate and delayed paragraph recall for all 3 carbohydrates (compared with placebo); the poorer the baseline memory or beta cell function, the greater the improvement (correlation between beta cell function and improvement in delayed paragraph recall: r-0.50, P:0.03). Poor beta cell function correlated with improvement for all carbohydrates in visuomotor task performance but not on an attention task.Glucose regulation was associated with cognitive performance in elderly subjects with normal glucose tolerance. Dietary carbohydrates (potatoes and barley) enhanced cognition in subjects with poor memories or beta cell function independently of plasma glucose.

This study determined whether the effect of all-trans-retinoic acid (t-RA) on markers of cholinergic differentiation in a murine septal cell line, SN56.B5.G4, differed depending upon the cell’s proliferative status. To develop a model of non-proliferating cells, aphidicolin, a DNA α-polymerase inhibitor, was used. Cessation of proliferation by aphidicolin increased intracellular choline and acetylcholine (ACh) levels in the absence of change to choline acetyltransferase (ChAT) activity and mRNA and vesicular ACh transporter (VAChT) mRNA. Importantly, the response to t-RA differed depending upon proliferative status. Consistent with previous reports, t-RA increased ChAT and VAChT mRNA, ChAT activity and intracellular ACh levels in proliferating SN56 cells with no effect on intracellular choline levels. When cells were treated with t-RA while undergoing proliferative arrest, an additive effect of combined treatment was observed on ACh levels; nevertheless, this was only accompanied by an increase in choline levels, VAChT and ChAT mRNAs, but not ChAT activity. Indeed, aphidicolin treatment completely suppressed the t-RA-induced increase in ChAT activity observed in proliferating cells. To explore the response to t-RA in post-mitotic cells, a sequential treatment of aphidicolin and t-RA was employed. t-RA treatment was ineffective in increasing ACh and choline levels, over and above that observed with the aphidicolin treatment alone. Comparable to the combined treatment, sequential treatment lead to an increase in ChAT mRNA without any increase in ChAT activity. In conclusion, both the magnitude and the mechanism(s) of action whereby t-RA enhances the cholinergic phenotype of SN56 cells is dependent upon the cell’s proliferative status.

Objective To evaluate whether a nutrient-fortified fluid-thickening agent (Pablum, H. J. Heinz Co of Canada, North York, Ontario, Canada) replaces nutrients lost to food displacement associated with its use. Design Seven-day, investigator-weighted, food intake records were evaluated to determine the prevalence of nutrient inadequacy. Nutrient intakes, including and excluding those associated with Pablum, were assessed to determine the ability .of Pablum to protect from nutrient inadequacy. Subjects/setting Subjects (19 women and 2 men aged 69 to 109 years) were residents of a home for the aged or a chroniccare hospital who required pureed food and thickened fluids. Statistical analyses performed Probability analysis was used to estimate the prevalence of nutrient inadequacy for micronutrients and protein. Results Approximately 15% of consumed energy (mean±standard deviation: 1,534±310 kcal/day; 1.38±0.37 and 1.46±0.26 multiplied by basal metabolic rate for men and women) came from the thickener. If a nonfortified thickener was used, risk of inadequacy (percentage of sample) would be apparent for protein (16%), calcium (95%), thiamin (57%), riboflavin (28%), niacin (55%), and folate (47% for women and 97% for men); no risk was estimated for iron and vitamins A and C. The nutrients contained in Pablum reduced or eliminated the risk of inadequacy for some nutrients, including protein (8%), calcium (9%), thiamin (0%), riboflavin (0%), and niacin (0%). In contrast, inadequate consumption of water and folate occurred even when the contribution of Pablum was considered. Applications The use of a nutrient-fortified thickening agent has merit; however, the current formulation of Pablum does not allow for complete protection against nutrient inadequacy. J Am Diet Assoc. 2000;100;549-554 .

The digestibility and absorption of dietary triacylglycerols are dependent on a number of factors including their fatty acid profile. Data demonstrating poor bioavailability of dietary stearic acid would suggest that hydrogenated oil sources would have lower digestibility coefficients compared with their native oils. To test this hypothesis, postweanling rats were fed one of four diets, formulated to contain 40% of energy as fat (assuming complete bioavailability), for 14 d. The diets only differed by fat type, containing soybean oil (SBO), fully hydrogenated soybean oil (HSB), medium-chain triglyceride oil (MCT), or hydrogenated coconut oil (HCO). Rats fed HSB consumed more food during the last 6 d (155.2 +/- 2.7 g) than those in each of the other groups (MCT: 118.9 +/- 2. 2 g; HCO: 124.7 +/- 3.2 g; SBO: 123.8 +/- 2.3 g), yet, they did not gain more weight. Two-day fecal excretion was almost three times greater in HSB-fed rats than in rats fed any other diet (P < 0.0001) because HSB was very poorly available. The digestibility coefficients (a measure of bioavailability) of the four fats were: HSB (30.9 +/- 1.3%) < HCO (94.5 +/- 0.4%) < SBO (97.0 +/- 0.4%) < MCT (98.7 +/- 0.2%) (P < 0.0007). All rats compensated for the incomplete availability of the fats, as apparent absorbable energy consumed did not differ among diet groups. The present data suggest that HSB only contributes 11.6 kJ/g (most fats contribute approximately 37.7 kJ/g) and that not only manufactured fat substitutes, such as olestra, but also more conventional fats are incompletely available to the body. Foods that currently contain HSB may contribute much less utilizable fat and energy than presently realized.

The degree to which fatty acids modulate brain function beyond periods of rapid brain growth is poorly understood. Nevertheless, recent evidence suggests that dietary fatty acid composition influences numerous behaviors including body temperature regulation, pain sensitivity, feeding behavior including macronutrient selection, and cognitive performance. Importantly, alterations are observed in the absence of essential fatty acid (EFA) deficiency, beyond periods of rapid brain development, and at levels similar to those consumed by the North American population. Data suggest that the content of saturated fatty acids (SFAs), and not that of the EFAs, may be the important component of dietary fat mediating macronutrient selection and cognition under these experimental conditions. Yet, a direct role of SFAs in modulating brain functions has not been elucidated. A discussion of potential mechanisms which may directly involve the central nervous system, or may indirectly influence central processes via peripheral pathway(s) is presented.

Docosahexaenoic acid (22:6n-3) is the major brain n-3 polyunsaturated fatty acid and it is possible that docosahexaenoic acid is anti-inflammatory in the brain as it is known to be in other tissues. Using a combination of models including the fat-1 transgenic mouse, chronic dietary n-3 polyunsaturated fatty acid modulation in transgenic and wild-type mice, and acute direct brain infusion, we demonstrated that unesterified docosahexaenoic acid attenuates neuroinflammation initiated by intracerebroventricular lipopolysaccharide. Hippocampal neuroinflammation was assessed by gene expression and immunohistochemistry. Furthermore, docosahexaenoic acid protected against lipopolysaccharide-induced neuronal loss. Acute intracerebroventricular infusion of unesterified docosahexaenoic acid or its 12/15-lipoxygenase product and precursor to protectins and resolvins, 17S-hydroperoxy-docosahexaenoic acid, mimics anti-neuroinflammatory aspects of chronically increased unesterified docosahexaenoic acid. LC-MS/MS revealed that neuroprotectin D1 and several other docosahexaenoic acid-derived specialized pro-resolving mediators are present in the hippocampus. Acute intracerebroventricular infusion of 17S-hydroperoxy-docosahexaenoic acid increases hippocampal neuroprotectin D1 levels concomitant to attenuating neuroinflammation. These results show that unesterified docosahexaenoic acid is protective in a lipopolysaccharide-initiated mouse model of acute neuroinflammation, at least in part, via its conversion to specialized pro-resolving mediators; these docosahexaenoic acid stores may provide novel targets for the prevention and treatment(s) of neurological disorders with a neuroinflammatory component. Our study shows that chronically increased brain unesterified DHA levels, but not solely phospholipid DHA levels, attenuate neuroinflammation. Similar attenuations occur with acute increases in brain unesterified DHA or 17S-HpDHA levels, highlighting the importance of an available pool of precursor unesterified DHA for the production of enzymatically derived specialized pro-resolving mediators that are critical in the regulation of neuroinflammation.

Evidence is accumulating from in vitro and rodent studies that vitamin K plays a role in brain and could have a positive effect on cognitive function, especially during aging. The present study exa...

Evidence is accumulating that vitamin K could have a role in cognition, especially in aging. Using data from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge), a cross-sectional analysis was conducted to examine the associations between vitamin K status, measured as serum phylloquinone concentrations, and performance in verbal and non-verbal episodic memory, executive functions, and speed of processing. The sample included 320 men and women aged 70 to 85 years who were free of cognitive impairment. After adjustment for covariates, higher serum phylloquinone concentration (log-transformed) was associated with better verbal episodic memory performances (F ¼ 2.43, p ¼ 0.048); specifically with the scores (Z-transformed) on the second ( b ¼ 0.47; 95% confidence interval [CI] ¼ 0.13e0.82), third (b ¼ 0.41; 95% CI ¼ 0.06e0.75), and 20-minute delayed (b ¼ 0.47; 95% CI ¼ 0.12 e0.82) free recall trials of the RL/RI-16 Free and Cued Recall Task. No associations were found with nonverbal episodic memory, executive functions, and speed of processing. Our study adds evidence to the possible role of vitamin K in cognition during aging, specifically in the consolidation of the memory trace.

Assessment of long-term phylloquinone exposure is challenging in studies investigating vitamin K in health. Data are equivocal as to whether a single measurement of circulating phylloquinone would be adequate. The primary purpose of the present study was to validate the use of a single measurement of serum phylloquinone as a surrogate for long-term phylloquinone exposure in healthy older adults. Using data from the Québec Longitudinal Study on Nutrition and Successful Aging, the objectives were to: 1) determine the reproducibility of circulating phylloquinone over 2 y (n = 234); 2) calculate how a single measurement would rank or classify individuals and attenuate the regression coefficient between circulating phylloquinone and a health outcome; and 3) investigate the association of a single measurement of serum phylloquinone with long-term phylloquinone intakes assessed over the year prior to the blood draw (n = 228). The variance analysis based on 2 blood samples showed a fair to good reproducibility for serum phylloquinone (intra-class correlation = 0.49). The correlation coefficient between the ranking of individuals based on a single measurement of circulating phylloquinone and the "true" ranking would be 0.70. The multiple regression analysis showed that long-term phylloquinone intake was the strongest predictor of serum phylloquinone (t = 4.94; P0.001). The partial correlation coefficient (r = 0.32) was comparable with those reported in studies where blood sampling and diet recording were juxtaposed and/or multiple blood samples were used. The present study provides evidence that the use of a single measurement of circulating phylloquinone is adequate for assessing long-term phylloquinone exposure in healthy older adults.

particular, in the late-onset formsofAD,epigenetic alterationsmight play an important role in the pathophysiology of this disorder. The sulfur compound and dietary supplement S-adenosylmethionine (SAM) has been reported to have cytoprotective and antioxidant properties in the treatment ofAD.However, the underlyingmechanisms thatmayexplain the cellularprotective effects arenot fully understood.Methods: H 2O 2 -induced neuronal toxicity was characterized in SH-SY5Y human neuroblastoma cells by the decrease of cell viability using PrestoBlue assay (Invitrogen) and by the increase o f intracellular reactive oxygenspecies (ROS) level usingDCFH-DA(2’, 7’-dichlorodihydrofluorescin diacetate) assays.Hemeoxygenase-1mRNAexpressionwas assayedbyRT-PCR. The immunoblotting analysis is implicated for detecting phosphor-c-Jun, phosphor-AKT, andphosphor-ERK1/2 expression to check if the anti-apoptotic signal pathways could be activated by H 2 O 2 medium.Results: Pretreatment with0.01mg/mlSAMsignificantly suppressed theH2O2-inducedelevationof intracellular reactive oxygen species (ROS) level by100%and increased the cell viability by 10%after 24 hours treatment ofH 2O2 adding. Heme oxygenase-1 (HO-1)genewasup-regulatedbut phosphor-AKTwas inhibitedbypretreatment of 0.01 mg/ml SAM. Conclusions: Our results indicated that SAM may activate HO-1 gene expression to perform the protective effect on neuron through the signal of modulating the phospholation of AKT pathway. The epigenetic alterations on gene expression of SAM treatment may explain that provide a dietary supplement of SAMwill be an important part of the interface between the environment and the regulation of gene expression in neuron protection.