Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction
Introduction
Ageing is often associated with decline of cognitive functions. In the experimental animals, cognitive function can be evaluated by long-term potentiation (LTP) or behavior test (Bliss and Lomo, 1973, McKernan and Shinnick-Gallagher, 1997, Rogan et al., 1997). Compared with young rats, aged animals usually show a significant decrease of LTP. This decline of LTP was reflected on the behavioral deficits on the Morris water maze test (Kotani et al., 2003, Rosenzweig et al., 1997). Such decline of cognitive functions may be partly due to the age-dependent decrease of membrane n − 6 polyunsaturated fatty acid (PUFA), especially arachidonic acid (ARA) that is abundant in the hippocampal neurons (Lynch et al., 1994, McGahon et al., 1997, Murray and Lynch, 1998a, Soderberg et al., 1991). Even if the dietary intake of ARA is unchanged, the concentration of ARA in the neuronal membrane may decrease because of the increase of ARA peroxidation with ageing. Accordingly, it seems to be reasonable that water maze performance and synaptic plasticity can be improved with ARA dietary supplementation in the aged rats (Kotani et al., 2003, Murray and Lynch, 1998b). It is likely that membrane ARA is indispensable for the maintenance of cognitive function in the aged rats.
On the other hand, docosahexaenoic acid (DHA) is one of the n − 3 major PUFA that is abundant in the brain and retina. DHA is not only associated with learning-memory and vision (Birch et al., 2000, Carlson and Werkman, 1996), but also is useful for the prevention of ischemic brain damages by means of anti-thrombotic effect (Tsukada et al., 2000). DHA in the brain is known to show an age-dependent decrease like ARA (McGahon et al., 1999).
In humans, decreased cerebral concentration of ARA and DHA are seen with aging and Alzheimer's disease (Soderberg et al., 1991). The cognitive deficits are well known to be associated not only with ageing or Alzheimer's disease, but also with various organic brain diseases such as cerebral infarction, hemorrhage and traumatic brain injuries. Until now, there have been very few effective treatments for the cognitive dysfunction due to ageing, organic brain lesions, or Alzheimer's disease. Certain medicine can merely delay the progress of symptoms, but is not sufficient for improving these cognitive impairments.
The cognitive functions of rodents were assessed by the learning behaviors, while human cognitive function was clinically estimated by the neuropsychological test. Previous neuropsychological assessments of cognitive deficits suffered a lack of appropriately designed test batteries for quickly but precisely screening many human subjects in the clinical practice. However, the repeatable battery for the assessment of neuropsychological status (RBANS) is nowadays becoming a standard screening test battery, because it was designed to assess global neuropsychological functions in a brief administration time (Randolph et al., 1998). Using RBANS, one can precisely estimate five cognitive domains of interest: immediate memory, visuospatial/constructional ability, language, attention, and delayed memory.
Here, we have evaluated the effect of ARA and DHA supplementation upon cognitive dysfunctions due to ageing, organic brain lesions or Alzheimer's disease, using a Japanese version of RBANS neuropsychological test (Yamashima et al., 2002).
Section snippets
Participants
A total of 40 out-patients of Minami-gaoka Hospital with a chief complaint of amnesia were initially registered in this study. However, one subject with ARA and DHA supplementation dropped out from the study for complaining mild diarrhea in the initial few days. In the end, the remaining 39 patients participated in this study.
Out of 39 patients studied, 21 patients (12 male, 9 female, 68.1 ± 6.3 years old, mean ± S.D.) were diagnosed as mild cognitive impairment (MCI) according to the modified
RBANS test
Standard score profiles of Japanese version of RBANS indexes were collected from 292 normal subjects, as summarized in Fig. 1. Scores of the 12 subtests in the normal population were shown in Fig. 1A, while those of the five cognitive domains were shown in Fig. 1B. Index scores of the normal population showed an age-dependent decrease, especially in immediate memory, attention and delayed memory indexes. As the score showed a decrease especially over 7th decade, aged subjects over 50 years old
Discussion
In this protocol, we studied whether dietary PUFA supplementation can improve cognitive dysfunction. Cognitive functions of the four groups (MCI-A, MCI-P, organic and AD) were evaluated by the Japanese version of RBANS neuropsychologjcal test (Yamashima et al., 2002), before and after the PUFA supplementation. The immediate memory score of the AD group being significantly lower than MCI-A, showed no improvement (Fig. 3). However, the immediate memories of the MCI-A and organic groups were
Acknowledgements
This project was supported by grants from the Japan Foundation for Ageing and Health, and Narishige Neuroscience Research Foundation (to SK), and the Japan Ministry of Education, Science and Technology (to TY).
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