Dietary fatty acids, age-related cognitive decline, and mild cognitive impairment

Currently available epidemiological evidence suggested that an increase of saturated fatty acids (SFA) could have negative effects on cognitive functions, while increased polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) may be protective against cognitive decline. In a Southern Italian elderly population from the Italian Longitudinal Study on Aging (ILSA), a clear reduction of risk of age-related cognitive decline (ARCD) has been found with elevated intake of PUFA and MUFA. Furthermore, in the ILSA, while dietary fatty acids intakes were not associated with incident mild cognitive impairment (MCI), high PUFA intake appeared to have borderline non-significant trend for a protective effect against the development of MCI. These epidemiological findings on predementia syndromes, i.e. MCI or ARCD, together with a recent randomised controlled trial on a possible effect on cognitive and depressive symptoms of ω-3 PUFA supplementation in patients with very mild AD, suggested a possible role of fatty acids intake in maintaining adequate cognitive functioning and possibly in preventing or delaying the onset of dementia.     

Vascular risk factors, alcohol intake, and cognitive decline

Since the therapeutic options currently available have demonstrated limited efficacy, the search for preventive strategies for cognitive decline and dementia is mandatory. A possible role of vascular and lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer’s disease, AD) or vascular origin. At present, cumulative evidence suggested that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia, and AD. Among vascular-related factors, metabolic syndrome has been associated with the risk of cognitive decline and overall dementia. Moderate alcohol drinking has been proposed as a protective factor against MCI and dementia in several longitudinal studies, but contrasting findings also exist. However, in most cases, these were only observational studies, and results are awaited from large multicenter randomized clinical trials in older persons. At present, vascular risk factor management, lifestyle changes, and drugs could be employed together to delay the onset of dementia syndromes.     

Effects of Dietary Food Components on Cognitive Functions in Older Adults

Population aging has recently been an important issue as the number of elderly people is growing worldwide every year, and the extension of social security costs is financially costly. The increase in the number of elderly people with cognitive decline is a serious problem related to the aging of populations. Therefore, it is necessary to consider not only physical care but also cognitive patterns in the future care of older adults. Since food contains a variety of bioactive substances, dietary patterns may help improve age-related cognitive decline. However, the relationship between cognitive function and individual food components remains ambiguous as no clear efficacy or mechanism has been confirmed. Against this background, this review summarizes previous reports on the biological process of cognitive decline in the elderly and the relationship between individual compounds in foods and cognitive function, as well as the role of individual components of food in cognitive function, in the following order: lipids, carotenoids, vitamins, phenolic compounds, amino acids, peptides, and proteins. Based on the research presented in this review, a proper diet that preserves cognitive function has the potential to improve age-related cognitive decline, Alzheimer’s disease, and Parkinson’s disease. Hopefully, this review will help to trigger the development of new foods and technologies that improve aging and cognitive functions and extend the healthy life span.     

Nutritional Status Is Associated With Clinical Progression in Alzheimer's Disease: The NUDAD Project

ObjectiveIn cognitively normal adults, nutritional parameters are related to cognitive decline and incidence of dementia. Studies on the role of nutrition in predementia stages subjective cognitive decline and mild cognitive impairment, and mild stages of Alzheimer's disease (AD) dementia in a clinical setting are lacking. In the absence of a curative treatment, this evidence is important for targeting nutritional factors to potentially prevent or delay further cognitive decline. Our aim is to investigate associations of nutritional parameters with clinical progression in patients ranging from those who are cognitively normal to those who have AD dementia.DesignLongitudinal.Setting and ParticipantsMemory clinic, 551 patients (219 with subjective cognitive decline, 135 with mild cognitive impairment, and 197 with AD dementia), mean age 64 ± 8 years.MeasurementsWe assessed body mass index, fat-free mass, Mini-Nutritional Assessment, and dietary intake with the Dutch Healthy Diet food frequency questionnaire and the 238-item healthy life in an urban setting (HELIUS) food frequency questionnaire at baseline. Cox proportional hazard models were used to evaluate associations of nutritional parameters with clinical progression. Additional analyses were restricted to patients who were amyloid positive.ResultsWe observed clinical progression in 170 patients (31%) over 2.2 ± 0.9 years. Poorer Mini-Nutritional Assessment score [hazard ratio (95% confidence interval) 1.39 (1.18–1.64)], lower body mass index [1.15 (0.96–1.38)], lower fat-free mass [1.40 (0.93–2.10)], and a less healthy dietary pattern [1.22 (1.01–1.48)] were associated with a higher risk of clinical progression. Similar effect sizes were found in patients who were amyloid positive.Conclusions and ImplicationsPoorer nutritional status and a less healthy dietary pattern are associated with a higher risk of clinical progression. This study provides support for investigating whether improving nutritional status can alter the clinical trajectory of AD.     

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration.     

Characterization of Vitamin D Status in Older Persons with Cognitive Impairment

Vitamin D exerts a role in the maintenance of cognitive abilities and in frailty. Although several studies evaluated the interactions between vitamin D and cognitive impairment, results were conflicting. In a cohort of community-dwelling older persons, we described the association between vitamin D levels and cognitive decline and all-cause dementia evaluating frailty’s contribution. Our cohort included 509 adults, aged 64–92 years: 176 patients with mild cognitive impairment (MCI), 59 with Alzheimer’s Disease (AD), 26 with idiopathic Normal Pressure Hydrocephalus (iNPH), 133 with mixed dementia (MD) and 115 without cognitive decline. Frailty was measured by frailty index, and serum 25-hydroxyvitamin D concentrations through electrochemiluminescence immunoassays. We found a significant association between vitamin D levels and Mini Mental State Examination independently of cognitive impairment, age, sex and frailty. The patients with dementia (AD and MD) showed the lowest vitamin D levels, while MCI patients showed higher levels than the other groups. The most severe deficiency was observed in MD patients, the most aged as well as cognitively and functionally impaired. In conclusion, in our community-dwelling older persons investigated for a suspected cognitive impairment, we observed an association between vitamin D levels and cognitive decline, regardless of the frailty status.     

Oral administration of chicken breast extract increases brain carnosine and anserine concentrations in rats

Carnosine (β-alanyl-L-histidine) and its derivative anserine (β-alanyl-1-methyl-L-histidine) are antioxidants and putative neurotransmitters in the brain. These dipeptides are rich in the commercially available supplement chicken breast extract (CBEX). To clarify the effects of CBEX on the brain, we examined whether single oral administration of CBEX (20 ml/kg) affects brain dipeptide and free amino acid concentrations in male Wistar rats. CBEX significantly and time-dependently increased carnosine and anserine levels in the plasma (at 120 min after injection, increase rates were 2976 and 4142%, respectively), hippocampus (64 and 78%), and hypothalamus (188 and 120%), but not in cerebral cortex. Significant and time-dependent increases in citrulline in the hippocampus (49%) and hypothalamus (41%) demonstrated generation of nitric oxide due to the increased carnosine and/or anserine levels in these brain regions. These findings suggest that CBEX modifies brain functions by increasing levels of these dipeptides.     

Oral administration of chicken breast extract increases brain carnosine and anserine concentrations in rats

Carnosine (beta-alanyl-L-histidine) and its derivative anserine (beta-alanyl-1-methyl-L-histidine) are antioxidants and putative neurotransmitters in the brain. These dipeptides are rich in the commercially available supplement chicken breast extract (CBEX). To clarify the effects of CBEX on the brain, we examined whether single oral administration of CBEX (20 ml/kg) affects brain dipeptide and free amino acid concentrations in male Wistar rats. CBEX significantly and time-dependently increased carnosine and anserine levels in the plasma (at 120 min after injection, increase rates were 2976 and 4142%, respectively), hippocampus (64 and 78%), and hypothalamus (188 and 120%), but not in cerebral cortex. Significant and time-dependent increases in citrulline in the hippocampus (49%) and hypothalamus (41%) demonstrated generation of nitric oxide due to the increased carnosine and/or anserine levels in these brain regions. These findings suggest that CBEX modifies brain functions by increasing levels of these dipeptides.     

Homocysteine and cognitive function in institutionalised elderly

Summary Background Several cross–sectional, case–control and prospective studies revealed a relation between homocysteine and cognitive function or dementia. These studies included either patient populations or healthy, community– dwelling elderly people. Aim of the study In this study we tested the hypothesis that homocysteine was inversely associated with cognitive function in a population of institutionalised elderly (aged ≥ 60 y; n = 157). Methods For testing this hypothesis baseline data of a recently conducted intervention study in institutionalised elderly (median age 83 years) were used. Cognitive function was evaluated by the cognitive subscale of the Alzheimer's disease Assessment Scale (ADAS–cog). The association between fasting plasma homocysteine level and cognitive function was investigated by multiple linear regression analysis. Results In the crude model homocysteine concentration was not significantly related to ADAS–cog score (β = 0.061; p = 0.45).Age was found to be related to ADAS–cog score (β = 0.161; p < 0.05). Adjusting for age did however not result in a relation between homocysteine and cognitive function. Conclusions In our study no association was found between homocysteine and cognitive function in a population of very old institutionalised subjects.     

Risk factors and neurodegenerative mechanisms in stroke related dementia

Considerable evidence indicates that systemic vascular diseases are associated with neurodegenerative processes preceding cognitive decline and dementia. Conditions such as hypertension, diabetes, atrial fibrillation, ischemic heart disease, dyslipidaemia and obesity have propensity to induce strokes, which increase risk of dementia up to five-fold in the elderly. The link between vascular diseases and clinical Alzheimer's disease (AD) also exists but pathological confirmation has often been lacking. However, more than 30% of stroke survivors will develop dementia within two years. Transient ischaemic attacks and silent infarcts may unmask neurodegenerative processes characterized by primary pathologies such as those found in AD. Cerebral infarction and neurodegenerative pathologies are additive and accelerate dementia. Medial temporal atrophy is a strong predictor of dementia and also appears a feature in demented stroke survivors with minimal AD pathology. The atrophy is attributed to selective smaller cell volumes in the hippocampus and likely frontal lobe that may reflect loss of neuronal arborization and connectivity. Therapeutic strategies that maintain or restore functional morphology in surviving neurons could prevent further cognitive decline in post stroke and ageing related dementias.     

Association of Plasma Phospholipids with Age-Related Cognitive Impairment: Results from a Cross-Sectional Study

Decreased concentration of phospholipids were observed in brain tissue from individuals with dementia compared with controls, indicating phospholipids might be a key variable in development of age-related cognitive impairment. The reflection of these phospholipid changes in blood might provide both reference for diagnosis/monitoring and potential targets for intervention through peripheral circulation. Using a full-scale targeted phospholipidomic approach, 229 molecular species of plasma phospholipid were identified and quantified among 626 senile residents; the association of plasma phospholipids with MoCA score was also comprehensively discussed. Significant association was confirmed between phospholipid matrix and MoCA score by a distance-based linear model. Additionally, the network analysis further observed that two modules containing PEs were positively associated with MoCA score, and one module containing LPLs had a trend of negative correlation with MoCA score. Furthermore, 23 phospholipid molecular species were found to be significantly associated with MoCA score independent of fasting glucose, lipidemia, lipoproteins, inflammatory variables and homocysteine. Thus, the decreased levels of pPEs containing LC-PUFA and the augmented levels of LPLs were the most prominent plasma phospholipid changes correlated with the cognitive decline, while alterations in plasma PC, PS and SM levels accompanying cognitive decline might be due to variation of lipidemia and inflammatory levels.     

IANA task force on nutrition and cognitive decline with aging

Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta analyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.     

Subjective Cognitive Decline,Cognitive Reserve Indicators,and the Incidence of Dementia

ObjectiveBoth cognitive reserve and subjective cognitive decline are closely related to the risk of dementia. We investigated whether cognitive reserve can modify the risk of dementia developing from subjective cognitive decline.DesignLongitudinal population-based study.Setting and ParticipantsThe prospective study analyzed data from 2099 participants aged 65 or over from the Cognitive Function and Ageing Study–Wales (CFAS-Wales).MethodsDementia was ascertained through the comprehensive judgment symptoms of geriatric mental state automated geriatric examination for computer assisted taxonomy (GMS-AGECAT). Subjective cognitive decline was evaluated by 2 questions in the baseline interview. Cognitive reserve indicators were derived from 3 previously identified factors: early life education, mid-life occupational complexity, and late-life cognitive activities. We used logistic regression models to estimate dementia risk in relation to subjective cognitive decline and indicators of cognitive reserve. The interaction between subjective cognitive decline and cognitive reserve were evaluated by additive and multiplicative scales.ResultsBaseline subjective cognitive decline and low cognitive reserve significantly increased the risk of dementia, after 2 years of follow-up. There was an additive interaction between subjective cognitive decline and cognitive reserve [the relative excess risk due to interaction = −0.63, 95% confidence interval (CI) = −0.89 to −0.36, P for additive interaction <0.001]. There was no multiplicative interaction between subjective cognitive decline and cognitive reserve indicator (P = .138). Statistically significant association between subjective cognitive decline and dementia was found only in the low-level and medium-level cognitive reserve group (OR = 3.78, 95% CI = 1.50–9.55 and OR = 3.64, 95% CI = 1.09–12.2, respectively), but not in the high-level groups.Conclusion and ImplicationsCognitive reserve attenuated subjective cognitive decline associated risk of developing dementia. This finding suggests the need for greater emphasis on detecting prodromal dementia when older patients having lower cognitive reserve present with subjective cognitive decline.     

Imidazole dipeptides in experimental alcohol-induced myopathy.

Rats were chronically fed a nutritionally complete liquid diet containing 35% of total calories as either ethanol, or (for the controls) an isocaloric amount of glucose. After 6 weeks of treatment, the feeding regime induced skeletal muscle myopathy as characterised by reductions in muscle weight and RNA content. Ethanol preferentially affected the metabolically glycolytic plantaris (Type II fibre-predominant) muscle of the rat, compared with the metabolically oxidative soleus (Type I fibre-predominant). The changes in the plantaris were associated with increases in the concentration (mumol per g wet weight) of anserine (18%) and carnosine (50%). No significant changes were seen for the concentrations of either anserine or carnosine in the soleus muscle. The total contents (mumol per muscle) of carnosine and anserine in the plantaris were not significantly altered by ethanol treatment, though a significant decrease in anserine content (30%) occurred in the soleus. It is concluded that reductions in imidazole dipeptide content, considered to be antioxidants and/or intracellular buffering agents, are not mediating factors in the development of chronic experimental myopathy.     

Specific Nutritional Biomarker Profiles in Mild Cognitive Impairment and Subjective Cognitive Decline Are Associated With Clinical Progression: The NUDAD Project

ObjectivesNutritional insufficiencies have been associated with cognitive impairment. Understanding whether nutritional biomarker levels are associated with clinical progression could help to design dietary intervention trials. This longitudinal study examined a panel of nutritional biomarkers in relation to clinical progression in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI).Design, setting and participantsWe included 299 patients without dementia (n = 149 SCD; age 61 ± 10 years, female 44%, n = 150 MCI; age 66 ± 8 years, female 38%). Median (interquartile range) follow-up was 3 (2-5) years.MethodsWe measured 28 nutritional biomarkers in blood and 5 in cerebrospinal fluid (CSF), associated with 3 Alzheimer's disease pathologic processes: vascular change (lipids), synaptic dysfunction (homocysteine-related metabolites), and oxidative stress (minerals and vitamins). Nutritional biomarker associations with clinical progression to MCI/dementia and cognitive decline based on the Mini-Mental State Examination score were evaluated using Cox proportional hazard models and linear mixed models. We used partial least squares Cox models (PLS-Cox) to examine nutritional biomarker profiles associated with clinical progression.ResultsIn the total group, high high-density lipoprotein (HDL) levels were associated with clinical progression and cognitive decline. In SCD, high folate and low bilirubin levels were associated with cognitive decline. In MCI, low CSF S-adenosylmethionine (SAM) and high theobromine were associated with clinical progression to dementia and high HDL, cholesterol, iron, and 1,25(OH)₂ vitamin D were associated with cognitive decline. PLS-Cox showed 1 profile for SCD, characterized by high betaine and folate and low zinc associated with clinical progression. In MCI, a profile with high theobromine and HDL and low triglycerides and a second profile with high plasma SAM and low cholesterol were associated with risk of dementia.Conclusion and ImplicationsHigh HDL was most consistently associated with clinical progression. Moreover, different nutritional biomarker profiles for SCD and MCI showed promising associations with clinical progression. Future dietary (intervention) studies could use nutritional biomarker profiles to select patients, taking into account the disease stage.     

Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia

BACKGROUND: Evidence supports an independent association between plasma total homocysteine concentrations and the risk of vascular disease. Recent epidemiologic studies reappraised the possibility that vascular risk factors might play a role in the pathogenesis not only of vascular dementia (VaD) but also of Alzheimer disease (AD). OBJECTIVE: The objective was to investigate the relations of mild cognitive impairment, AD, and VaD with blood homocysteine, folate, and vitamin B-12. DESIGN: The study population consisted of 314 consecutive subjects, 228 of whom were eligible for analyses. Plasma total homocysteine, serum folate, and serum vitamin B-12 concentrations were measured in 55 nondemented elderly control subjects, 81 mildly cognitively impaired subjects (Clinical Dementia Rating: 0.5), and 92 demented patients prevalently in a mild disease stage and with a clinical diagnosis of AD (n = 74) or VaD (n = 18). RESULTS: Subjects in the lowest folate tertile had significantly higher adjusted odds ratios (ORs) for mild cognitive impairment (OR: 3.1; 95% CI: 1.2, 8.1) and dementia (3.8; 1.3, 11.2). Hyperhomocysteinemia was significantly associated with dementia (adjusted OR: 4.3; 1.3, 14.7) and AD (adjusted OR: 3.7; 1.1, 13.1). In subjects with a Clinical Dementia Rating of 0.5, the mean (+/- SE) Mini-Mental State Examination score was significantly lower (P < 0.05) in the highest homocysteine tertile (24.5 +/- 0.5) than in the lowest tertile (26.6 +/- 0.5). No significant associations were found between minimum medial temporal lobe thickness or leukoaraiosis and any biochemical measure in the dementia and AD groups. CONCLUSIONS: These findings suggest that relative folate deficiency may precede AD and VaD onset. Hyperhomocysteinemia might also be an early risk factor for cognitive decline in the elderly, but its role in dementia development must be addressed in future longitudinal studies.     

Cognitive intervention programmes on patients affected by Mild Cognitive Impairment: A promising intervention tool for MCI?

Purpose  

This paper examines and reviews studies on the efficacy of computer-based cognitive intervention programmes in the elderly affected by Mild Cognitive Impairment (MCI). MCI patients are at higher risk to progress to dementia. Recent effort has been made to slow the cognitive decline and delay the onset of dementia in this population.     

Lower omega-3 fatty acid intake and status are associated with poorer cognitive function in older age: A comparison of individuals with and without cognitive impairment and Alzheimer's disease

Abstract

Objectives

Various strands of evidence suggest that low intake of omega-3 fatty acids increases risk of cognitive decline and dementia. The present study investigated differences in dietary intake and blood plasma content of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in individuals with cognitive impairment no dementia (CIND), individuals with Alzheimer's disease (AD), and healthy volunteers (HV).

Methods

A total of 135 individuals aged between 55 and 91 years (19 AD, 55 CIND, and 61 HV) were assessed predominantly within a hospital setting.

Results

Compared with age and sex-matched HV, individuals with AD or CIND performed poorly on a majority of tests of cognitive function. Impairment was greatest for delayed and verbal recognition memory. CIND individuals were less impaired than AD individuals. Omega-3 intake and the percentage of EPA and DHA in plasma phosphatidylcholine (PC) showed a similar pattern (AD < HV, with intermediate scores for CIND). Across the whole sample, and after controlling for age, years of education, level of socio-economic deprivation, and gender, omega-3 intake, plasma PC DHA, and plasma PC EPA were all significant positive predictors of memory functioning.

Discussion

These results are consistent with the possibility that omega-3 fatty acid nutrition has an impact on cognitive decline, but could equally be explained by dietary changes that occurred after onset of cognitive decline. It is also possible that the results could be explained by unknown confounding factors.     

Falls,Cognitive Impairment,and Gait Performance: Results From the GOOD Initiative

Objectives

Falls are highly prevalent in individuals with cognitive decline. The complex relationship between falls and cognitive decline (including both subtype and severity of dementia) and the influence of gait disorders have not been studied. This study aimed to examine the association between the subtype (Alzheimer disease [AD] versus non-AD) and the severity (from preclinical to moderate dementia) of cognitive impairment and falls, and to establish an association between falls and gait parameters during the course of dementia.

Omega 3 fatty acids and cognitive health in older people

Oily fish and other sources of long-chain n-3 polyunsaturated fatty acids (n-3 LCPs) have been proposed as protective against dementia and age related cognitive impairment. The basic mechanisms underlying these proposed benefits have been postulated and experimental studies supporting the plausibility of the putative effects have been published. Observational epidemiological and case control studies also largely support a protective role of fish consumption on cognitive function with advancing age, albeit with important unexplained heterogeneity in findings. In this review we report the findings of the latest Cochrane review on the benefits of n-3 LCP supplementation on cognitive function among cognitively healthy older people and expand the review by including trials conducted with individuals with prevalent poor cognitive function or dementia. We identified seven relevant trials, four among cognitively healthy older people, and three among individuals with pre-existing cognitive decline or dementia, and overall conclude that there is no evidence to support the routine use of n-3 LCPs supplements for the prevention, or amelioration, of cognitive decline in later life. We identified several challenges in the design of intervention studies for the prevention of dementia and cognitive decline in older people that require careful consideration especially in recruitment and retention in long-term trials. Whether the lack of agreement in findings from mechanistic and observational data and from intervention studies reflects a real absence of benefit on cognitive function from n-3 LCP supplementation, or whether it reflects intrinsic limitations in the design of published studies remains open to question.