Household physical activity is positively associated with gray matter volume in older adults.

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.

Sex differences in the relationship between dietary pattern adherence and cognitive function among older adults: findings from the NuAge study.

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 (ß = - 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.

Cardiovascular risk and encoding-related hippocampal connectivity in older adults.

BACKGROUND: Cardiovascular conditions contribute to brain volume loss, reduced cerebrovascular health, and increased dementia risk in aging adults. Altered hippocampal connectivity has also been observed in individuals with cardiovascular conditions, yet the functional consequences of these changes remain unclear. In the present study, we collected functional magnetic resonance imaging data during memory encoding and used a psychophysiological interaction analysis to examine whether cardiovascular burden, indexed using the Framingham risk score, was associated with encoding-related hippocampal connectivity and task performance in cognitively-intact older adults between 65 and 85 years of age. Our goal was to better understand the early functional consequences of vascular and metabolic dysfunction in those at risk for cognitive decline. RESULTS: High Framingham risk scores were associated with lower total brain volumes. In addition, those with high Framingham risk scores showed an altered relationship between left hippocampal-medial prefrontal coupling and task performance compared to those with low Framingham risk scores. Specifically, we found a significant interaction of Framingham risk and learning on connectivity between the left hippocampus and primarily left midline prefrontal regions comprising the left ventral anterior cingulate cortex and medial prefrontal cortex. Those with lower Framingham risk scores showed a pattern of weaker connectivity between left hippocampal and medial prefrontal regions associated with better task performance. Those with higher Framingham risk scores showed the opposite pattern; stronger connectivity was associated with better performance. CONCLUSIONS: Findings from the current study show that amongst older adults with cardiovascular conditions, higher Framingham risk is associated with lower brain volume and altered left hippocampal-medial prefrontal coupling during task performance compared to those with lower Framingham risk scores. This may reflect a compensatory mechanism in support of memory function and suggests that older adults with elevated cardiovascular risk are vulnerable to early Alzheimer disease-like dysfunction within the episodic memory system.

Nutrition as a component of dementia risk reduction strategies.

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.

Vascular risk factor burden correlates with cerebrovascular reactivity but not resting state coactivation in the default mode network.

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 (r(2) = 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.

Unesterified docosahexaenoic acid is protective in neuroinflammation.

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.

Relationship between diet quality and cognition depends on socioeconomic position in healthy older adults.

Both diet quality and socioeconomic position (SEP) have been linked to age-related cognitive changes, but there is little understanding of how the socioeconomic context of dietary intake may shape its cognitive impact. We examined whether equal adherence to "prudent" and "Western" dietary patterns, identified by principal components analysis, was associated with global cognitive function [Modified Mini-Mental State Examination (3MS)] in independently living older adults with different SEPs (aged 68-84 y; n = 1099). The interaction of dietary pattern adherence with household income, educational attainment, occupational prestige, and a composite indicator of SEP combining all 3 was examined in multiple-adjusted mixed models over 3 y of follow-up in participants of the NuAge study (Quebec Longitudinal Study on Nutrition and Successful Aging). Adherence to the prudent pattern (vegetables, fruits, fish, poultry, and lower-fat dairy products) was related to higher 3MS scores at recruitment only in the upper categories of income [parameter estimate (B): 0.56; 95% CI: 0.11, 1.01], education (B: 0.44; 95% CI: 0.080, 0.80), or composite SEP (B: 0.37; 95% CI: 0.045, 0.70). High prudent pattern adherence was associated with less cognitive decline only in those with low composite SEP (B: 0.25; 95% CI: 0.0094, 0.50). Conversely, adherence to the Western pattern (meats, potatoes, processed foods, and higher-fat dairy products) was associated with more cognitive decline (B: -0.23; 95% CI: -0.43, -0.032) only in those with low educational attainment. In summary, among individuals with equivalent diet quality, the magnitude and characteristics of the diet-cognition relationship depended on their socioeconomic circumstances. These results suggest that interventions promoting retention of cognitive function through improved diet quality would provide maximum benefit to those with relatively low SEP.

Associations between circulating cardiovascular disease risk factors and cognitive performance in cognitively healthy older adults from the NuAge study.

Introduction: Cardiovascular disease risk factors (CVRFs) contribute to the development of cognitive impairment and dementia. Methods: This study examined the associations between circulating CVRF biomarkers and cognition in 386 cognitively healthy older adults (mean age = 78 ± 4 years, 53% females) selected from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). Memory, executive function, and processing speed were assessed at baseline and 2-year follow-up. CVRF biomarkers included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides, glucose, insulin, high sensitivity C-reactive protein (hs-CRP), homocysteine, protein carbonyls, and cortisol. Linear mixed models were used to determine associations between individual CVRF biomarkers and cognition at both time points. Results: HDL-C was most consistently associated with cognition with higher values related to better performance across several domains. Overall, stronger and more consistent relationships between CVRF biomarkers and cognition were observed in females relative to males. Discussion: Findings suggest that increases in the majority of circulating CVRFs are not associated with worse cognition in cognitively healthy older adults.

A single measurement of serum phylloquinone is an adequate indicator of long-term phylloquinone exposure in healthy older adults.

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; 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.

A minimum of six days of diet recording is needed to assess usual vitamin K intake among older adults.

There is a growing interest in the role of vitamin K in health, especially in aging populations. Knowledge of inter- and intra-individual variability of dietary vitamin K intake could be useful to accurately assess usual intake and rank participants in epidemiological studies. Our objectives were to: 1) estimate the variance components of vitamin K intake; 2) investigate whether day of the week, season, and energy intake are factors related to intra-individual variance; and 3) calculate the requisite number of days to achieve desired degrees of accuracy for estimating individual vitamin K intake, ranking individuals and estimating regression coefficient. Vitamin K intake was assessed in 939 older adults (67-84 y) enrolled in the Québec Longitudinal Study on Nutrition and Successful Aging study using 2 sets of 3 nonconsecutive multiple-pass 24-h dietary recalls (24HR) collected 6 mo apart. Each set included 2 weekdays and one weekend day. Intra- to inter-individual variance ratios for vitamin K intake were 3.2 (95% CI = 2.6-3.9) overall, 2.6 (95% CI = 2.1-3.5) for men, and 3.7 (95% CI = 2.9-5.0) for women. Day of the week (weekdays) and season (May to October) were positively and significantly associated with vitamin K intake but explained a negligible part of intra-individual variation (<1%). Adjusting for energy intake explained <7% of variance and did not affect the variance ratio. Six to 13 24HR are required to properly rank individuals according to their usual vitamin K intake and limit attenuation of the regression coefficient. These results should be considered in studies planning to assess vitamin K intakes in older adults.

The Association Between Dietary Pattern Adherence, Cognitive Stimulating Lifestyle, and Cognitive Function Among Older Adults From the Quebec Longitudinal Study on Nutrition and Successful Aging.

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.

Lower Thalamic Blood Flow Is Associated With Slower Stride Velocity in Older Adults.

BACKGROUND: Gait deficits are associated with brain atrophy and white matter hyperintensities (WMH) - both markers of underlying cerebral small vessel disease (SVD). Given reduced subcortical cerebral blood flow (CBF) is prevalent in SVD, we tested the hypothesis that regional CBF is positively associated with gait performance among older adults. METHODS: Thirty-two older adults (55-80 years) with at least one vascular risk factor were recruited. We assessed gait during 2 consecutive walking sequences using a GAITRite system: (1) at a self-selected pace, and (2) while performing a serial subtraction dual-task challenge. We quantified CBF using pseudo-continuous arterial spin labeling MRI within 4 regions of interest: putamen, pallidum, thalamus, and hippocampus. We investigated associations between gait characteristics and overall CBF adjusting for age, sex, and height in an omnibus approach using multivariate analysis of variance, followed by regression analysis with each individual region. We also conducted further regression analyses to investigate associations between gait characteristics and frontal lobe CBF. Sensitivity analyses examined how the observed associations were modified by WMH, executive function, and depressive symptoms. A change of 10% in the model's adjusted r2 and effect size was considered as a threshold for confounding. RESULTS: Overall subcortical CBF was not associated with self-paced gait. When examining individual ROI, gait velocity was directly related to thalamic CBF (p = 0.026), and across all gait variables the largest effect sizes were observed in relation to thalamic CBF. In the dual-task condition, gait variables were not related to CBF in either the omnibus approach or individual multiple regressions. Furthermore, no significant associations were observed between frontal CBF and gait variables in either the self-paced or dual-task condition. Sensitivity analyses which were restricted to examine the association of velocity and thalamic CBF identified a cofounding effect of depressive symptoms which increased the effect size of the CBF-gait association by 12%. CONCLUSION: Subcortical hypoperfusion, particularly in regions that comprise central input/output tracts to the cortical tissue, may underlie the association between gait deficits and brain aging.

The TNF-alpha-238G > a single-nucleotide polymorphism protects against memory decline in older adults with type 2 diabetes.

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.

Dietary influences on cognitive function with aging: from high-fat diets to healthful eating.

Human epidemiologic studies provide convincing evidence that dietary patterns practiced during adulthood are important contributors to age-related cognitive decline and dementia risk. Diets high in fat, especially trans and saturated fats, adversely affect cognition, while those high in fruits, vegetables, cereals, and fish are associated with better cognitive function and lower risk of dementia. While the precise physiologic mechanisms underlying these dietary influences are not completely understood, modulation of brain insulin activity and neuroinflammation likely contribute. Not surprisingly, deficits in cognitive functions, especially those dependent on the medial temporal lobes, are apparent in type 2 diabetes mellitus (T2DM). Special care in food selection at meals should be exercised by those with T2DM since ingestion of rapidly absorbed, high-glycemic index carbohydrate foods further impairs medial temporal lobe function, with food-induced increases in oxidative stress and cytokine release likely explaining the association between food ingestion and reduction in cognitive function in those with T2DM.

Changes in type of foodservice and dining room environment preferentially benefit institutionalized seniors with low body mass indexes.

OBJECTIVE: To compare energy intakes in seniors with cognitive impairment residing in long-term care and receiving meals by bulk (cafeteria style with waitress service) vs traditional tray delivery systems and determine subject characteristics that identify responsiveness to type of foodservice provided. DESIGN AND SUBJECTS/SETTING: Usual energy intakes were compared in subjects residing in cognitive impairment units in either the old (tray delivery, n=23) or new (bulk delivery, n=26) nursing home at Baycrest, a teaching facility associated with University of Toronto Medical School. INTERVENTION: Changes to foodservice and physical environment (from institutional to more home-like environment). MAIN OUTCOME MEASURES: Twenty-one consecutive day investigator-weighed energy and macronutrient intakes and behavioral function (London Psychogeriatric Rating Scale). STATISTICAL ANALYSES PERFORMED: Analysis of variance determined mean differences in intake and regression analyses identified predictors of sensitivity to type of food delivery systems. RESULTS: Higher 24-hour total (P<0.001) and dinner (P<0.001) energy intakes in subjects receiving bulk compared to tray delivery were predominantly associated with greater carbohydrate intakes (P<0.001). Higher energy, carbohydrate, and protein, but not fat intakes, with bulk delivery were more apparent in individuals with lower body mass indexes (BMIs) (food delivery by BMI interaction, all P values <0.05). CONCLUSIONS: High-risk, cognitively impaired individuals with low BMI benefited the most from the changed foodservice and physical environment, whereas individuals with higher BMIs did not show substantive changes in intake. Bulk foodservice and a home-like dining environment optimize energy intake in individuals at high risk for malnutrition, particularly those with low BMIs and cognitive impairment.

Brain Function Is Linked to LDL Cholesterol in Older Adults with Cardiovascular Risk.

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.

Energy-containing nutritional supplements can affect usual energy intake postsupplementation in institutionalized seniors with probable Alzheimer's disease.

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.

Studies of the effects of high fat diets on cognitive function in a rat model.

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.

High-fat diets, insulin resistance and declining cognitive function.

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.

Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity.

The genetically obese Zucker rat is a widely investigated model of pathological changes associated with type 2 diabetes. To assess cognitive function, obese and lean Zucker rats were tested on a variable-interval delayed alternation test of learning and memory. There were no group differences in learning the alternation rule or at short intervals, but obese rats were impaired at longer intervals where performance is hippocampus dependent. Plasma membrane association of the insulin sensitive glucose transporter, GLUT4, was reduced in the hippocampus of obese rats in the absence of changes in total GLUT4 and insulin receptor expression. These results parallel those of human studies in pointing to the susceptibility of the hippocampus and related structures to the adverse environment of diabetes mellitus.