Effect of Polyunsaturated Fatty Acids on the Evolution of Cognitive ability in Elderly Patients with Alzheimer’s Disease

Research Article

J Cardiovasc Disord. 2015;2(1): 1007.

Effect of Polyunsaturated Fatty Acids on the Evolution of Cognitive ability in Elderly Patients with Alzheimer’s Disease

Takashi Yamazaki*, Ken Nagata, Daiki Takano,Mayumi Saito, Tomomi Shinoda, Rena Muraoka,Yuchi Satoh, Yumi Fujimaki, and Tetsuya Maeda

Department of Neurology, Research Institute for Brain and Vessels, Japan

*Corresponding author: Takashi Yamazaki, Department of Neurology, Research Institute for Brain and Blood Vessels 6-10 Senshu-Kubota-Machi, Akita 010-0874, Japan

Received: October 29, 2014; Accepted: February 23, 2015; Published: February 24, 2015


As the disease modifying therapy is not yet available for Alzheimer’s disease (AD), the management of modifiable Vascular Risk Factors (VRFs) including lipid metabolism is now considered to be the best strategy to minimize the impact of AD lesions, especially in elderly subjects.

Objective: To elucidate the effect of Polyunsaturated Fatty Acids (PUFAs) on the cognitive ability, we investigated the relationship between the plasma PUFA profile and neuropsychological performance in elderly AD patients.

Methods: Present study was based on133 elderly patients (51 men and 82 women) with probable AD, and their mean age was 78.6 years. Mini-mental State Exam (MMSE) and clock drawing test were used for neuropsychological evaluation. Blood samples were obtained for the measurement of PUFA profiles. Neuropsychological evaluation was repeated with one-year interval in 49 subjects, who were classified into two categories; stable group in which the MMSE score was c\unchanged or improved and deteriorating group in which the MMSE score worsened. A Receiver Operating Characteristic (ROC) curve was used to evaluate the relationship between the EPA/AA ratio and the evolution of cognitive ability.

Results: Total MMSE score correlated positively with the Eicosapentaenoic Acid (EPA)/ Arachidonic Acid (AA) ratio, and negatively with AA concentration. In the ROC curve analysis, the threshold EPA/AA ratio was estimated at 0.67 for the stable MMSE score with 66% sensitivity and 70% specificity [Odds Ratio (OR) = 4.43].

Conclusion: The EPA/AA ratio can be regarded as a predictive marker for the preservation of cognitive ability in elderly AD patients.

Keywords: Vascular Risk Factors; Alzheimer’s Disease; Eicosapentaenoic Acid (EPA); Arachidonic Acid (AA); Polyunsaturated Fatty Acid (PUFA); EPA/ AA Ratio


According to the epidemiological studies, Vascular Risk Factors (VRFs) including hypertension, diabetes, dyslipidemia, heart failure and cerebrovascular lesions are associated with the onset and progression of Alzheimer’s Disease (AD) [1-2]. Such VRFs are also known to be the strong risk for vascular dementia and stroke, and they are regarded as common modifiable risk factors for AD and vascular dementia [3]. Since the disease modifying therapy is not yet available in the management of AD patients, treating modifiable VRFs is now considered to be the best strategy to minimize the impact of AD lesions, especially in elderly subjects [3].

The role of nutrition, a potentially modifiable vascular factor, and particularly that of dietary Polyunsaturated Fatty Acids (PUFA) has been drawing increasing attention for the prevention of cognitive decline and dementia. A number of epidemiological, clinical and experimental studies suggested the protective effects of the long chain omega-3 PUFAs such as Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) against coronary heart disease, arrhythmia atherosclerosis and hypertension [4-7].In addition to the vascular effects, the long chain omega-3 PUFAs are considered to be crucial to brain development and normal brain functioning [6]. Plasma omega-3 PUFAs were inversely related to the risk of dementia and depression [8]. Several epidemiological studies showed that fish consumption which is the primary dietary source of omega-3 PUFAs was associated with a reduced risk of cognitive decline and dementia [9-14]. Although the previous studies suggested that PUFAs were associated with the cognitive function in elderly subjects, the relationship between the PUFA profile and evolution of cognitive function in AD patients is still to be clarified. In the present study, we analyzed the PUFA profile in relation to the cognitive performance in Japanese elderly AD patients.

Subjects and Methods

The present study was observational clinical study focusing on the role of PUFAs as a clinical marker for the evolution of cognitive changes in probable AD patients.Weenrolled133 patients (51 men and 82 women) who were diagnosed as having probable AD according to the NINCDS-ADRDA criteria. The irmean age was 78.6 years. Inclusion criteria were diagnosis of probable AD and general health status that would not interfere with the patient’s ability to visit our memory clinic in the Research Institute for Brain and Blood Vessels. Exclusion criteria were non-AD dementia, residence in a long-term care facility at the time of screening, and a history of stroke, cancer, liver disease, severe arrhythmia, major psychiatric disorders, or other major central nervous system diseases. This study was approved by the institution ethics committee, and all subjects provided informed written consent.

Fasting blood samples were collected from all subjects at baseline. Laboratory tests included measurements of Fasting Blood Sugar (FBS), insulin, low-density lipoprotein cholesterol (LDL-cholesterol), High-Density Lipoprotein cholesterol (HDL-cholesterol), plasma PUFA concentration including EPA, DHA and Arachidonic Acid (AA), Brain Natriuretic Peptide (BNP) as well as Apo Ee4. EPA/AA and ω-3/ω-6 ratios were calculated based on the plasma fatty acid composition that was determined by the capillary gas chromatography. Quartile analysis was added to the evaluation of the relationship between the MMSE score and EPA/AA ratio.

Neuropsychological evaluation included the Mini-Mental State Exam (MMSE) [15] and the 5-point Clock Drawing Test (CDT), which has a sensitivity of 86.7% and a specificity of 92.7% for detecting AD-associated cognitive decline [16]. In 49 subjects, the neuropsychological evaluation was carried out repeatedly with oneyear interval. All patients were on donepezil (5mg/day) during the observation period. According to the difference in the total MMSE score between the baseline and follow-up evaluations, those subjects were classified into the2 groups: stable group in whom the MMSEs core was unchanged or improved as compared with the baseline, and deterioration group in whom the MMSEs core was worsened.

Gender differences in the baseline demographic, vascular and neuropsychological parameters were evaluated with the Χ2 test for categorical variables and with the wilcoxon test. Spearman rank correlation coefficient was used in the evaluation of the relationship between cognitive performance and the demographic and laboratory data. Wilcoxon test was used in the evaluation of the effect of PUFA profile on the risk of cognitive decline between stable and deterioration groups. Independent measures analysis of variance was used to explore the relationship between the EPA/AA ratio and cognitive decline in the follow-up study. The cut-off value of the EPA/ AA ratio for distinguishing cognitive stability from deterioration was calculated using the Receiver Operating Characteristic (ROC) curve. All probability values of 5% or less (two-sided) were considered significant. These statistical analyses were performed using SAS statistical software (version 11.2; SAS Inc., Cary, NC).


The mean baseline MMSE and CDT scores were 15.9 ± 5.3 and 2.7 ± 1.5, respectively. There was no significant difference in the mean age, blood pressure, presence of ApoE4, LDL-cholesterol, FBS, insulin HbA1c, and BNP between men and women. The EPA and DHA concentration did not differ between men and women, whereas the AA concentration was significantly higher in women than in men. The baseline MMSE score was significantly greater in men than in women (Table 1).