Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia.

BACKGROUND: Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia. METHODS: Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3-4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. 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 enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively). CONCLUSIONS: High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03056508 .

Better cognitive performance following a low-glycaemic-index compared with a high-glycaemic-index carbohydrate meal in adults with type 2 diabetes.

AIMS/HYPOTHESIS: 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. SUBJECTS AND METHODS: 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. RESULTS: 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 (p<0.05) 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. CONCLUSIONS/INTERPRETATION: 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.

Dietary protein, carbohydrate, and fat enhance memory performance in the healthy elderly.

BACKGROUND: Dietary carbohydrates can improve memory. Whether these effects are related to elevations in blood glucose or to energy ingestion is unknown. OBJECTIVES: Our objectives were to determine 1) the influence of isoenergetic protein-, carbohydrate-, and fat-containing drinks on cognitive performance and 2) whether the time period after ingestion affects cognition. DESIGN: After fasting overnight, 11 men and 11 women aged 61-79 y consumed either a 300-mL drink containing 774 kJ as pure protein (whey), carbohydrate (glucose), or fat (safflower oil) or a nonenergy placebo on 4 separate mornings. Cognitive tests were administered 15 and 60 min after ingestion of the drinks. Plasma glucose and serum insulin concentrations were measured. RESULTS: Only the carbohydrate drink increased blood glucose (P < 0.0001). Compared with the placebo, all 3 macronutrients improved delayed paragraph recall (PR) (P < 0.001) and improved or tended to improve immediate PR (P < 0.04) 15 min after ingestion. Beneficial effects on other cognitive tests were confined to one or more of the macronutrients: carbohydrate improved Trail Making Test (Trails) performance at 60 min (P = 0.02) and tended to improve Trails at 15 min (P = 0.04) and PR at 60 min in men, carbohydrate and fat improved or tended to improve performance on Trails at 15 and 60 min in subjects with poor baseline scores (r > -0.41, P < 0.03), fat tended to improve attention at 60 min (P < 0.05), and protein reduced the rate of forgetting on the PR at 15 min (P = 0.002). CONCLUSIONS: Energy intake from protein, carbohydrate, or fat can enhance memory independently of elevations in blood glucose. Each macronutrient may also exert unique effects on cognition.

Shift in diurnal feeding patterns in nursing home residents with Alzheimer's disease.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Meal delivery practices do not meet needs of Alzheimer patients with increased cognitive and behavioral difficulties in a long-term care facility.

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.

Glucose treatment reduces memory deficits in young adult rats fed high-fat diets.

Feeding rats high-fat diets for 3 months produces a widespread cognitive deficit that affects performance on a wide range of learning and memory tasks. The present study tested the hypothesis that this effect is related to a fat-induced impairment in glucose metabolism. Following 3 months of dietary intervention (20% by weight fat diets, composed primarily of either beef tallow or soybean oil versus standard laboratory chow), male Long-Evans rats were tested on a variable interval delayed alternation (VIDA) task that measures learning and memory functions that differentially involve specific brain regions. Relative to rats fed chow, rats consuming the high-fat diets were impaired on all aspects of VIDA performance. Following baseline testing, rats were maintained on their respective diets and the effect of glucose administration (100 mg/kg BW; i.p.) was examined. For the next 6 days, animals alternately received injections of saline or glucose 30 min prior to VIDA testing. Glucose treatment improved performance, with the effect being most pronounced at the longer intertrial intervals where task performance is sensitive to hippocampal impairment. Importantly, the beneficial effect of glucose were confined to those animals consuming the high-fat diets and were not observed in rats fed chow. These results demonstrate that glucose administration can overcome those deficits associated with hippocampal function in rats fed high-fat diets and are consistent with the hypothesis that high-fat diets, in part, mediate their effect through the development of insulin resistance and glucose intolerance.

Cognitive performance is associated with glucose regulation in healthy elderly persons and can be enhanced with glucose and dietary carbohydrates.

BACKGROUND: A glucose drink has been shown to improve memory in persons with poor glucose regulation and poor cognition. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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 [glucose > potatoes > barley > placebo (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. CONCLUSIONS: 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.

Cholinergic differentiation triggered by blocking cell proliferation and treatment with all-trans-retinoic acid.

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 alpha-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.

Nutrient contribution of infant cereals used as fluid thickening agents in diets fed to the elderly.

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 chronic-care 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.

Nutrients as trophic factors in neurons and the central nervous system: role of retinoic acid.

In multicellular organisms, death, survival, proliferation, and differentiation of a given cell depend on signals produced by neighboring and/or distant cells, resulting in the coordinated development and function of the various tissues. In the nervous system, control of cell survival and differentiation is achieved through the action of a distinct group of polypeptides collectively known as neurotrophic factors. Recent findings support the view that trophic factors also are involved in the response of the nervous system to acute injury. By contrast, nutrients are not traditionally viewed as potential trophic factors; however, there is increasing evidence that at least some influence neuronal differentiation. During development the brain is responsive to variations in nutrient supply, and this increased sensitivity or vulnerability of the brain to nutrient supply may reappear during neuronal repair, a period during which a rapid membrane resynthesis and reestablishment of synthetic pathways occur. To further evaluate the potential of specific nutrients to act as pharmacologic agents in the repair of injured neurons, the effects of retinoic acid, an active metabolite of vitamin A, and its role as a trophic factor are discussed. This literature review is intended to provide background information regarding the effect of retinoic acid on the cholinergic phenotype and the differentiation of these neurons and to explain how it may promote neuronal repair and survival following injury.

The effects of high fat diets and environmental influences on cognitive performance in rats.

As part of a continuing investigation of the relationship between dietary factors and cognitive function, the present study examined the combined effects of environmental influences and high-fat diets on learning and memory. Following 3 months of dietary (20% by weight fat diets, composed primarily of either beef tallow or soybean oil versus standard laboratory chow) and environmental treatments (standard, enriched or impoverished), subjects were tested on a variable interval delayed alternation (VIDA) task which measures learning and memory functions that differentially involve specific brain regions. The results confirmed the negative effects of high fat diets, relative to chow, on all aspects of VIDA performance and showed that environmental enrichment overcame deficits associated with dietary fat. Housing rats fed high-fat diets in an impoverished environment did not further exacerbate cognitive deficits observed in such rats living under standard conditions. By comparison, chow-fed rats exhibited no benefit associated with the enriched environment on any aspect of task performance, and only a transitory learning impairment when housed in an impoverished environment. The results show that high fat diets and environmental conditions influence cognitive function and that these two factors interact with one another to produce different profiles of benefits and impairments.

CCK-A receptor antagonists have selective effects on nutrient-induced food intake suppression in rats.

To provide additional support to the hypothesis that only dietary protein (Pro; chicken egg albumin) and not amino acids (AA; patterned after albumin), carbohydrates (CHO; cornstarch), or fats (Fat; corn oil) produces a satiating effect via CCK receptors, two CCK-A receptor antagonists (PD-140,548 and devazepide) were coadministered with each nutrient. Given alone [4 ml intragastrically (ig)] Pro (1.0 g), AA (1.0 g), CHO (1.4 g), and Fat (2.4 g) suppressed (P < 0.05) food intake on average during the first 2 h of feeding by 1.4 (36%), 1.5 (48%), 1.0 (33%), and 1.2 g (41%), respectively. Devazepide (0.5 mg/kg) and PD-140,548 (1.0 mg/kg) given alone increased food intake during 0-2 h by 0.7 g (18%) and during 0-1 h by 0.5 g (15%), respectively. When coadministered with PD-140,548 (1.0 mg/kg ip), the suppression of food intake caused by Pro was modulated during 0-2 h by 57% (Pro x drug interaction, P < 0.05), but AA-, CHO-, and Fat-induced suppression of feeding was not affected (nutrient x drug interaction, P > 0.05). Devazepide (0.5 mg/kg ip) did not modulate AA-, CHO-, and Fat-induced food intake suppression during any time period (nutrient x drug interaction, P > 0.05). These studies provide additional evidence that CCK-A receptors play a role in Pro (albumin) but not AA-, CHO (cornstarch)-, or Fat (corn oil)-induced food intake suppression in rats.

Poor digestibility of fully hydrogenated soybean oil in rats: a potential benefit of hydrogenated fats and oils.

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.

Dietary saturated fatty acids and brain function.

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.

Current and projected rates of hip fracture in Canada.

OBJECTIVE: To determine the current values and estimate the projected values (to the year 2041) for annual number of proximal femoral fractures (PFFs), age-adjusted rates of fracture, rates of death in the acute care setting, associated length of stay (LOS) in hospital, and seasonal variation by sex and age in elderly Canadians. DESIGN: Hospital discharge data for fiscal year 1993-94 from the Canadian Institute for Health Information were used to determine PFF incidence, and Statistics Canada population projections were used to estimate the rate and number of PFFs to 2041. SETTING: Canada. PARTICIPANTS: Canadian patients 65 years of age or older who underwent hip arthroplasty. OUTCOME MEASURES: PFF rates, death rates and LOS by age, sex and province. RESULTS: In 1993-94 the incidence of PFF increased exponentially with increasing age. The age-adjusted rates were 479 per 100,000 for women and 187 per 100,000 for men. The number of PFFs was estimated at 23,375 (17,823 in women and 5552 in men), with a projected increase to 88,124 in 2041. The rate of death during the acute care stay increased exponentially with increasing age. The death rates for men were twice those for women. In 1993-94 an estimated 1570 deaths occurred in the acute care setting, and 7000 deaths were projected for 2041. LOS in the acute care setting increased with advancing age, as did variability in LOS, which suggests a more heterogeneous case mix with advancing age. The LOS for 1993-94 and 2041 was estimated at 465,000 and 1.8 million patient-days respectively. Seasonal variability in the incidence of PFFs by sex was not significant. Significant season-province interactions were seen (p < 0.05); however, the differences in incidence were small (on the order of 2% to 3%) and were not considered to have a large effect on resource use in the acute care setting. CONCLUSIONS: On the assumption that current conditions contributing to hip fractures will remain constant, the number of PFFs will rise exponentially over the next 40 years. The results of this study highlight the serious implications for Canadians if incidence rates are not reduced by some form of intervention.

Dietary fatty acid composition induces comparable changes in cardiolipin fatty acid profile of heart and brain mitochondria.

The fatty acid profile of cardiolipin (CL) from brain and cardiac mitochondria was measured to determine whether CL isolated from these two tissue sources responded similarly to alterations in dietary fat composition. Male Wistar rats were fed 20% (w/w) diets containing 2 to 12% (w/w) 18:2n-6 for four weeks. Despite higher baseline levels of CL 18:2n-6 in cardiac (54 +/- 1% of total fatty acids) compared to brain (13 +/- 1%) mitochondria, CL 18:2n-6 levels increased in proportion to dietary 18:2 levels. The degree of change in 18:2n-6 was comparable with both tissues showing an approximate 1.5- to 2-fold increase. The time course of changes in CL fatty acid profile was examined in a subsequent experiment in which animals were fed 20% (w/w) fat diets containing either 3 or 15% alpha-linoleate. Changes in cardiac CL 18:1, 18:2n-6, and 22:6n-3 levels were observed within one week of feeding. While statistically significant differences were not observed in brain CL until the second week of feeding, the time course did not differ substantively from that observed in heart. The results from this study suggest that while baseline fatty acid profile of cardiac and neural CL differ, mitochondria from both tissues show comparable sensitivity to changes in dietary fat composition. Furthermore, it would appear that the turnover rate of fatty acids in CL is similar in both tissues.

Cognitive impairment in rats fed high-fat diets: a specific effect of saturated fatty-acid intake.

One-month-old rats were fed 1 of 4 high-fat diets (20% fat) or chow (4.5% fat) for 3 months. Dietary saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) fatty acids varied such that their independent effects on cognitive performance could be tested. Rats were tested on a variable-interval delayed-alternation task. Impairment in both the ability to learn the basic alternation rule and remembering trial-specific information over time was observed in rats fed the experimental diets relative to those fed chow. The degree of impairment was highly associated with the level of SFAs fed and independent of the MUFAs or PUFAs. Dietary fat altered brain phosphatidylcholine fatty-acid profile, but the membrane changes did not correlate with cognitive impairment. The results demonstrate that cognitive impairment is directly associated with SFA intake but suggest that the mechanism is independent of bulk brain membrane compositional changes.

Dietary fat composition and age affect synaptosomal and retinal phospholipid fatty acid composition in C57BL/6 mice.

The purpose of this study was (i) to determine whether dietary fat-induced differences in neural and retinal membranes occur when dietary fat treatment is implemented in aged animals and (ii) to characterize the effect of long-term differences in dietary fat on neural and retinal membrane composition. For the first objective, young (six-week-old) and old (95-week-old) mice were randomly assigned to beef tallow (TAL) or soybean oil (SBO) diets for eight weeks. For the second objective, young (four-week-old) mice consumed either TAL or SBO diets for 99 weeks. Young and old mice challenged with a change in dietary fat for an eight-week period showed both diet and age effects on neural and retinal phospholipid fatty acid composition (P < 0.05). In addition, significant diet by age interactions were evident. In mice that consumed TAL and SBO diets throughout their life, only retinal phosphatidylethanolamine (PE) 18:2n-6 and neural phosphatidylserine 22:5n-6, PE 18:2n-6 and phosphatidylcholine 18:2n-6 differed between dietary treatments (P < 0.05). Neither the unsaturation index nor the n-6/n-3 ratio was affected by diet. Neural and retinal phospholipid fatty acid composition were responsive to changes in dietary fat even when the treatment was implemented beyond developmental or post-weanling stages. In contrast, when mice consumed TAL or SBO diets throughout their life, fewer differences in phospholipid fatty acid composition were detected, suggesting that the effect of the dietary treatment was mitigated by aging.

Interactions between MPTP-induced and age-related neuronal death in a murine model of Parkinson's disease.

Abiotrophy is hypothesized to explain the onset and time course of deficits in Parkinson's disease (PD) Abiotrophy includes: 1) exposure to agent(s) causing the death of dopaminergic nigrostriatal neurons (DNSns), 2) gradual death of DNSns with age, 3) summation of 1) and 2) until DNSn numbers fall below a threshold for detectable neurological deficits. Murine DNSn death following methyl-phenyl-tetrahydropyridine (MPTP) exposure occurs according to an exponential relationship while age-related death of DNSns occurs according to a second exponential relationship. Summing the two exponential losses overestimates experimental DNSn death showing a simple abiotrophic model is not sufficient. Aged murine DNSns greatly increase their dopamine synthesis and the density of their striatal axon terminals which may explain the above threshold. Murine DNSns die gradually after MPTP exposure and L-deprenyl treatment rescues MPTP-damaged DNSns by a previously undiscovered action, altering the abiotrophic interactions and possibly explaining the slowed progression of PD found with deprenyl treatment.