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Life Extension Magazine March 2009

Cognitive function

Maintaining cognitive health in an ageing society.

A significant concern associated with growing old is the loss of cognitive function, resulting in dementia. Fortunately, the current research on ageing indicates that cognitive decline is not an inevitable function of the ageing process. Moreover, individuals can take steps to maintain cognitive health throughout life. This paper reviews the research findings and recommendations for maintaining cognitive health that were presented at a meeting sponsored by the Alliance for Health and the Future in November 2003. The meeting, ‘Placing Cognitive Health on Europe’s Social and Economic Agenda’, reviewed the current state of knowledge about cognitive health and discussed its implications for an ageing Europe. Although the brain, for reasons that remain unclear, changes with age, a growing body of research suggests that social engagement, intellectual stimulation, and physical activity play a key role in maintaining cognitive health and preventing cognitive decline. As the number of older people increases and people live longer, developing and implementing strategies for maintaining cognitive health should be a priority for both individuals and societies.

J R Soc Health. 2004 May;124(3):119-21

Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats.

Epidemiological studies suggest that diets with a high intake of vegetables and fruits may reduce the incidence of degenerative disorders including Alzheimer’s disease. Berries are some of the popular fruits consumed worldwide. They are considered to be rich in anthocyanin pigments, a group belonging to the flavonoids, a widespread class of phenolic compounds. Anthocyanins have notorious pharmacological properties, and have been used in humans for therapeutic purposes. The present experiments were performed to study the possible effects of prolonged administration of lyophilised Vaccinium berries (blueberry, bilberry) on cognitive performance using step-down inhibitory avoidance, open field, elevated plus-maze, and radial maze tasks. During this experiment the rats consumed approximately 3.2 mg kg(-1)day (oral), of the anthocyanins. The lyophilised berries were administered for 30 days before first training. The present study showed that lyophilised berries significantly enhanced short-term memory, but not long-term memory in the inhibitory avoidance task, and induced an increase in the number of crossings in the first exposure to the open field. However, treated rats did not present any improvement of memory retention in open field habituation. Additionally, prolonged treatment with lyophilised berries did not have any significant effects in the elevated plus-maze task. Another interesting finding was that lyophilised berries improved working memory in the radial maze, with significant differences observed during sessions 1-2 and 4, but did not alter reference memory in this task. These results suggest that lyophilised berries may be beneficial in the prevention of memory deficits, one of the symptoms related to AD, and corroborate previous findings showing that flavonoids present effects in several learning paradigms.

Pharmacol Res. 2005 Dec;52(6):457-62

The putative role of free radicals in the loss of neuronal functioning in senescence.

One of the hallmarks of the aging process is a loss of sensitivity in central neuronal receptors to agonist stimulation. This appears to be especially true in central (hippocampal, striatal) muscarinic cholinergic systems and in the striatal dopamine systems. For these two systems, any decline in their sensitivity can be of extreme importance in determining the behavioral capabilities of the organism. Decrements in the striatal dopamine system may be reflected as motor behavioral deficits, while the central cholinergic systems play a major role in the processing of memory through the activation of muscarinic receptors (mAChR). Declines in the function of these receptors appear to be at least partially responsible for the marked deterioration of cognitive function in normal aging and, more notably, in Alzheimer’s disease (AD). Previous work has indicated only minimal success in improving performance in tasks that assess memory in senescent animals or humans with pharmacological agents which enhance cholinergic functioning. The present review describes research that indicates that two of the factors involved in this decline in receptor sensitivity include: (a) decreased receptor concentrations and (b) age-related decrements in signal transduction pathways. Studies are reviewed that indicate that the oxidative neural damage that occurs via kainic acid or ionizing radiation parallel those seen in aging. It is suggested that the common mechanism that may exist among all of the age-, disease-, excitatory amino acid- or radiation-induced deficits in neuronal transmission may involve free-radical-mediated alterations in membrane integrity through lipid peroxidation.

Integr Physiol Behav Sci. 1992 Jul-Sep;27(3):216-27

Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation.

Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K(+)-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca(45) buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging.

J Neurosci. 1999 Sep 15;19(18):8114-21

Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats.

During aging, reductions in hippocampal neurogenesis are associated with memory decline indicating a causal relationship. Indeed, insulin-like growth factor-1 (IGF-1), a major activator of the extracellular receptor kinase pathway that is central in learning and memory processes, is also a key modulator of hippocampal neurogenesis. Previously, we showed that age-related declines in spatial memory tasks can be improved by antioxidant-rich diets containing blueberries. In this study, to begin to understand the mechanisms responsible for the beneficial effects of blueberries, we assessed changes in hippocampal plasticity parameters such as hippocampal neurogenesis, extracellular receptor kinase activation, and IGF-1 and IGF-1R levels in blueberry-supplemented aged animals. Our results show that all these parameters of hippocampal neuronal plasticity are increased in supplemented animals and aspects such as proliferation, extracellular receptor kinase activation and IGF-1 and IGF-1R levels correlate with improvements in spatial memory. Therefore, cognitive improvements afforded by polyphenolic-rich fruits such as blueberries appear, in part, to be mediated by their effects on hippocampal plasticity.

Nutr Neurosci. 2004 Oct-Dec;7(5-6):309-16

Investigation of the effect of vinpocetine on cerebral blood flow and cognitive functions

INTRODUCTION: Vinpocetine has been widely used in the treatment of ischaemic cerebrovascular diseases and dementias of vascular type. Chronic cerebral hypoperfusion plays an important role in the development of certain types of dementia. In consequence of complex mode of action vinpocetine plays a significant role in the improvement of cerebral hypoperfusion. The symptoms of mild cognitive impairment considered as “predementia” are similar to those of dementia, although milder. AIMS: The authors investigated the characteristics of the blood flow parameters of patients with ischemic stroke and mild cognitive impairment both in resting conditions or following chemical stimulus as well as they investigated the severity of mental deterioration in the two patient groups. In a pilot study the authors examined the influence of 12-week long oral vinpocetine therapy on the blood flow parameters and cognitive functions in the two patient groups. METHODS: The authors studied the blood flow velocity of a. cerebri media in resting conditions and after 30 sec of breath holding with transcranial Doppler before treatment and after a 12-week long oral vinpocetine treatment. At the same time psychometric tests (MMSE, ADAS-Cog) were used in order to examine cognitive functions, while the general condition of the patients were scored by Clinical Global Impression (CGI) scale. RESULTS: After a 12-week long oral vinpocetine treatment the increase of blood flow velocity in resting conditions compared to the baseline values was significant in the vascular group. The percent increase of mean velocity after the breath holding TCD test showed a significant increase compared to the baseline in both patient groups. The authors found a significant improvement of cognitive functions after a 12-week long oral vinpocetine therapy using psychometric tests. The improvement was identical in both groups. The general condition of patients improved significantly according to both the investigator’s and the patients’ opinion; patients with mild cognitive impairment judged the improvement higher. CONCLUSIONS: Vinpocetine improved the cerebrovascular reserve capacity in both patient groups and favourably influenced the cognitive status and general condition of patients with chronic hypoperfusion. The authors recommend the use of vinpocetine for the treatment of patients with mild cognitive impairment.

Ideggyogy Sz. 2007 Jul 30;60(7-8):301-10

Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine.

Aged dogs demonstrate cognitive decline that is linked to brain aging. The purpose of the present study was to examine if a commercially available nutraceutical supplement that may be neuroprotective and contains phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine could improve cognitive function in aged beagles. Nine aged beagles were tested on performance on a delayed-non-matching-to-position task, which is a neuropsychological test of short-term visuospatial memory. All subjects were tested on 5 baseline sessions; then, to assess the supplement, a crossover design was used in which 1 group received the supplement and the other a control substance in the 1st phase, with treatment conditions being reversed in the 2nd phase. Performance accuracy was significantly improved in supplemented dogs compared with control dogs and the effect was long lasting. These findings suggest that the nutraceutical supplement can improve memory in aged dogs.

Can Vet J. 2008 Apr;49(4):379-85

Influence of phosphatidylserine on cognitive performance and cortical activity after induced stress.

The aim of this study was to investigate the effect of phosphatidylserine (PS) on cognition and cortical activity after mental stress. After familiarization, 16 healthy subjects completed cognitive tasks after induced stress in a test-re-test design (T1 and T2). Directly after T1, subjects were assigned double-blind to either PS or placebo groups followed by T2 after 42 days. At T1 and T2, cortical activity was measured at baseline and immediately after stress with cognitive tasks using electro-encephalography (EEG). EEG was recorded at 17 electrode positions and fast Fourier transforms (FFT) determined power at Theta, Alpha-1, Alpha-2, Beta-1 and Beta-2. Statistics were calculated using ANOVA (group x trial x time). The main finding of the study was that chronic supplementation of phosphatidylserine significantly decreases Beta-1 power in right hemispheric frontal brain regions (F8; P < 0.05) before and after induced stress. The results for Beta-1 power in the PS group were connected to a more relaxed state compared to the controls.

Nutr Neurosci. 2008 Jun;11(3):103-10

Aromas of rosemary and lavender essential oils differentially affect cognition and mood in healthy adults.

This study was designed to assess the olfactory impact of the essential oils of lavender (Lavandula angustifolia) and rosemary (Rosmarlnus officinalis) on cognitive performance and mood in healthy volunteers. One hundred and forty-four participants were randomly assigned to one of three independent groups, and subsequently performed the Cognitive Drug Research (CDR) computerized cognitive assessment battery in a cubicle containing either one of the two odors or no odor (control). Visual analogue mood questionnaires were completed prior to exposure to the odor, and subsequently after completion of the test battery. The participants were deceived as to the genuine aim of the study until the completion of testing to prevent expectancy effects from possibly influencing the data. The outcome variables from the nine tasks that constitute the CDR core battery feed into six factors that represent different aspects of cognitive functioning. Analysis of performance revealed that lavender produced a significant decrement in performance of working memory, and impaired reaction times for both memory and attention based tasks compared to controls. In contrast, rosemary produced a significant enhancement of performance for overall quality of memory and secondary memory factors, but also produced an impairment of speed of memory compared to controls. With regard to mood, comparisons of the change in ratings from baseline to post-test revealed that following the completion of the cognitive assessment battery, both the control and lavender groups were significantly less alert than the rosemary condition; however, the control group was significantly less content than both rosemary and lavender conditions. These findings indicate that the olfactory properties of these essential oils can produce objective effects on cognitive performance, as well as subjective effects on mood.

Int J Neurosci. 2003 Jan;113(1):15-38

Clinical and non-clinical investigations using positron emission tomography, near infrared spectroscopy and transcranial Doppler methods on the neuroprotective drug vinpocetine: a summary of evidences.

Vinpocetine (Cavinton, Gedeon Richter, Budapest) is widely used as a neuroprotective drug in the prevention and treatment of cerebrovascular diseases. Vinpocetine is a potent inhibitor of the voltage-dependent Na(+) channels and a selective inhibitor of the Ca(2+)/caldmoduline-dependent phosphodiesterase 1. The clinical efficacy has been supported by several previous studies. Positron emission tomography (PET) is a powerful method to evaluate the fate, the site of action, the pharmacological and physiological effects of a drug in the brain and other organs. We have demonstrated in monkey that the [11C]-labelled vinpocetine rapidly enters the brain after intravenous (i.v.) injection, the maximal uptake being approximately 5% of the total injected radioactivity. The distribution pattern of vinpocetine in the brain was heterogenous, with the highest uptake in the thalamus, basal ganglia and visual cortex. These findings were confirmed in healthy humans, where the i.v. administered [11C]-labelled vinpocetine had a similar distribution pattern. The highest uptake in the brain was 3.71% of the total administered radioactivity. Quite recently, we have shown that [11C]-labelled vinpocetine administered orally to healthy human volunteers also rapidly appears in the brain and shows a similar distribution pattern, the highest uptake being 0.71% of the total administered radioactivity. In two separate sets of clinical studies where chronic ischaemic post-stroke patients were either treated with a single infusion (Study 1) or with daily vinpocetine infusion for 2 weeks (Study 2), we have shown that vinpocetine increases the regional cerebral glucose uptake and to a certain extent glucose metabolism in the so-called peri-stroke region as well as in the relatively intact brain tissue. The 2-week-long treatment also increased the regional cerebral blood flow (CBF) especially in the thalamus, basal ganglia and visual cortex of the nonsymptomatic hemisphere. We have demonstrated the cerebral perfusion-enhancing and parenchymal oxygen extraction-increasing effects of vinpocetine in subacute ischaemic stroke patients by near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) methods.

J Neurol Sci. 2002 Nov 15;203-204:259-62

Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data.

This paper has reviewed the documentation on the clinical efficacy of choline alphoscerate, a cholinergic precursor, considered as a centrally acting parasympathomimetic drug in dementia disorders and in acute cerebrovascular disease. Thirteen published clinical trials, examining in total 4054 patients, have evaluated the use of choline alphoscerate in various forms of dementia disorders of degenerative, vascular or combined origin, such as senile dementia of the Alzheimer’s type (SDAT) or vascular dementia (VaD) and in acute cerebrovascular diseases, such as transitory ischemic attack (TIA) and stroke. Analysis has assessed the design of each study, in particular with respect to experimental design, number of cases, duration of treatment and tests used to evaluate drug clinical efficacy. Most of the ten studies performed in dementia disorders were controlled trials versus a reference drug or placebo. Overall, 1570 patients were assessed in these studies, 854 of which in controlled trials. As detected by validated and appropriate tests, such as Mini Mental State Evaluation (MMSE) in SDAT and Sandoz Clinical Assessment Geriatric (SCAG) in VaD, administration of choline alphoscerate significantly improved patient clinical condition. Clinical results obtained with choline alphoscerate were superior or equivalent to those observed in control groups under active treatment and superior to the results observed in placebo groups. Analysis stresses the clear internal consistency of clinical data gathered by different experimental situations on the drug effect, especially with regard to the cognitive symptoms (memory, attention) characterising the clinical picture of adult-onset dementia disorders. The therapeutic usefulness of choline alphoscerate in relieving cognitive symptoms of chronic cerebral deterioration differentiates this drug from cholinergic precursors used in the past, such as choline and lecithin. Three uncontrolled trials were performed with choline alphoscerate in acute cerebrovascular stroke and TIA, totalling 2484 patients. The results of these trials suggest that this drug might favour functional recovery of patients with cerebral stroke and should be confirmed in future investigations aimed at establish the efficacy of the drug in achieving functional recovery of patients with acute cerebrovascular disease.

Mech Ageing Dev. 2001 Nov;122(16):2041-55

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