Age Cognitive Function Research Articles

Age-related alterations in the modular organization of structural cortical network by using cortical thickness from MRI

Normal aging is accompanied by various cognitive functional declines. Recent studies have revealed disruptions in the coordination of large-scale functional brain networks such as the default mode network in advanced aging. However, organizational alterations of the structural brain network at the system level in aging are still poorly understood. Here, using cortical thickness, we investigated the modular organization of the cortical structural networks in 102 young and 97 normal aging adults. Brain networks for both cohorts displayed a modular organization overlapping with functional domains such as executive and auditory/language processing. However, compared with the modular organization of young adults, the aging group demonstrated a significantly reduced modularity that might be indicative of reduced functional segregation in the aging brain. More importantly, the aging brain network exhibited reduced intra-/inter-module connectivity in modules corresponding to the executive function and the default mode network of young adults, which might be associated with the decline of cognitive functions in aging. Finally, we observed age-associated alterations in the regional characterization in terms of their intra/inter-module connectivity. Our results indicate that aging is associated with an altered modular organization in the structural brain networks and provide new evidence for disrupted integrity in the large-scale brain networks that underlie cognition.

Acute effect of a high nitrate diet on brain perfusion in older adults

AimsPoor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and resultsIn this investigation we administered a high vs. low nitrate diet to older adults (74.7±6.9years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. ConclusionThese results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning.

Differential Protection among Fractionated Blueberry Polyphenolic Families against DA-, Aβ42- and LPS-Induced Decrements in Ca2+ Buffering in Primary Hippocampal Cells

It has been postulated that at least part of the loss of cognitive function in aging may be the result of deficits in Ca(2+) recovery (CAR) and increased oxidative/inflammatory (OX/INF) stress signaling. However, previous research showed that aged animals supplemented with blueberry (BB) extract showed fewer deficits in CAR, as well as motor and cognitive functional deficits. A recent subsequent experiment has shown that DA- or Abeta(42)-induced deficits in CAR in primary hippocampal neuronal cells (HNC) were antagonized by BB extract, and (OX/INF) signaling was reduced. The present experiments assessed the most effective BB polyphenol fraction that could protect against OX/INF-induced deficits in CAR, ROS generation, or viability. HNCs treated with BB extract, BB fractions (e.g., proanthocyanidin, PAC), or control medium were exposed to dopamine (DA, 0.1 mM), amyloid beta (Abeta(42), 25 muM) or lipopolysaccharide (LPS, 1 microg/mL). The results indicated that the degree of protection against deficits in CAR varied as a function of the stressor and was generally greater against Abeta(42) and LPS than DA. The whole BB, anthocyanin (ANTH), and PRE-C18 fractions offered the greatest protection, whereas chlorogenic acid offered the lowest protection. Protective capabilities of the various fractions against ROS depended upon the stressor, where the BB extract and the combined PAC (high and low molecular weight) fraction offered the best protection against LPS and Abeta(42) but were less effective against DA-induced ROS. The high and low molecular weight PACs and the ANTH fractions enhanced ROS production regardless of the stressor used, and this reflected increased activation of stress signals (e.g., P38 MAPK). The viability data indicated that the whole BB and combined PAC fraction showed greater protective effects against the stressors than the more fractionated polyphenolic components. Thus, these results suggest that, except for a few instances, the lesser the polyphenolic fractionation, the greater the effects, especially with respect to prevention of ROS and stress signal generation and viability.

White Matter in Aging and Cognition: A Cross-Sectional Study of Microstructure in Adults Aged Eighteen to Eighty-Three

Structural brain change and concomitant cognitive decline are the seemingly unavoidable escorts of aging. Despite accumulating studies detailing the effects of age on the brain and cognition, the relationship between white matter features and cognitive function in aging have only recently received attention and remain incompletely understood. White matter microstructure can be measured with diffusion tensor imaging (DTI), but whether DTI can provide unique information on brain aging that is not explained by white matter volume is not known. In the current study, the relationship between white matter microstructure, age, and neuropsychological function was assessed using DTI in a statistical framework that employed white matter volume as a voxel-wise covariate in a sample of 120 healthy adults across a broad age range (18–83). Memory function and executive function were modestly correlated with the DTI measures while processing speed showed the greatest extent of correlation. The results suggest that age-related white matter alterations underlie age-related declines in cognitive function. Mean diffusivity and fractional anisotropy in several white matter brain regions exhibited a nonlinear relationship with age, while white matter volume showed a primarily linear relationship with age. The complex relationships between cognition, white matter microstructure, and white matter volume still require further investigation.

Blockade of GABA(B) receptors completely reverses age-related learning impairment

Impaired cognitive functions are well-described in the aging process. GABA(B) antagonists can facilitate learning and memory in young subjects, but these agents have not been well-characterized in aging. Here we show a complete reversal of olfactory discrimination learning deficits in cognitively-impaired aged Fischer 344 rats using the GABA(B) antagonist CGP55845, such that drug treatment restored performance to that on par with young and cognitively-unimpaired aged subjects. There was no evidence that this improved learning was due to enhanced olfactory detection abilities produced by the drug. These results highlight the potential of targeting GABA(B) receptors to ameliorate age-related cognitive deficits and demonstrate the utility of olfactory discrimination learning as a preclinical model for testing novel therapies to improve cognitive functions in aging.

Caloric restriction improves memory in elderly humans

Animal studies suggest that diets low in calories and rich in unsaturated fatty acids (UFA) are beneficial for cognitive function in age. Here, we tested in a prospective interventional design whether the same effects can be induced in humans. Fifty healthy, normal- to overweight elderly subjects (29 females, mean age 60.5 years, mean body mass index 28 kg/m(2)) were stratified into 3 groups: (i) caloric restriction (30% reduction), (ii) relative increased intake of UFAs (20% increase, unchanged total fat), and (iii) control. Before and after 3 months of intervention, memory performance was assessed under standardized conditions. We found a significant increase in verbal memory scores after caloric restriction (mean increase 20%; P < 0.001), which was correlated with decreases in fasting plasma levels of insulin and high sensitive C-reactive protein, most pronounced in subjects with best adherence to the diet (all r values < -0.8; all P values <0.05). Levels of brain-derived neurotrophic factor remained unchanged. No significant memory changes were observed in the other 2 groups. This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects. Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity. Our study may help to generate novel prevention strategies to maintain cognitive functions into old age.

Global Functional Coupling of Resting EEG Rhythms is Abnormal in Mild Cognitive Impairment and Alzheimer’s Disease

Alzheimer’s disease (AD) is typically associated with an impairment of brain networks and global cognitive function in aging. In this vein, the present study tested the hypothesis that the functional coupling of resting cortical electroencephalographic (EEG) rhythms is progressively abnormal in amnesic mild cognitive impairment (MCI) and AD subjects. Eyes-closed resting EEG data were recorded (10–20 system) in 33 mild AD, 52 amnesic MCI, and 47 normal elderly subjects (Nold). EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha1 (8–10 Hz), alpha2 (10–13 Hz), beta1 (13–20 Hz), beta2 (20–30 Hz), and gamma (30–40 Hz). The global functional coupling of the EEG rhythms was indexed by means of spectral coherence for all combinations of electrode pairs (i.e., total coherence). The main results showed that the total coherence of delta rhythms was higher in the AD than the MCI group. It was also higher in the MCI than the Nold group. Furthermore, the delta total coherence was negatively correlated with global cognition (Mini Mental State Examination score) across the Nold, MCI, and AD subjects. Finally, the alpha1 total coherence was lower in the AD group than in the MCI and Nold groups. These results suggest that in the AD process an impairment of brain networks and global cognition is associated with a frequency-specific modulation of the global functional coupling of resting EEG rhythms.

Instability in the latency of P3a/P3b brain potentials and cognitive function in aging

Instability in performance is a prominent feature of aging. In this study, 133 participants evenly distributed across the adult lifespan underwent a three-stimulus event-related potentials (ERPs) paradigm, and instability in P3a/P3b latency and reaction time (RT) were measured. P3a is related to alertness or reorientation of attention and it was elicited by distractor stimuli. P3b is related to controlled attentional processes and it was triggered by target stimuli. Maximum-likelihood estimation (MLE) was used to quantify the level of variability in latency across the single sweep ERPs. The results revealed increased variability in RT but not in P3a/P3b latency with age. Variability in P3a/P3b latency was related to executive functions, and variability in RT to speed. Generally, the relationships tended to increase with age. It can be concluded that increased variability in RT with age is caused by instability in processes related to response execution and possibly response selection, but not stimulus classification. Further, the results indicate that intraindividual variability is not a uniform concept, but has unique explanatory value at the neurophysiological and behavioral level.

Dopamine and Aβ-Induced Stress Signaling and Decrements in Ca2+ Buffering In Primary Neonatal Hippocampal Cells Are Antagonized by Blueberry Extract

We have shown previously that dietary blueberry (BB) extract supplementation (S) reversed several parameters of neuronal and behavioral (e.g., cognition) aging in rodents. Additionally, findings indicate that COS-7 cells transfected with muscarinic receptor subtypes (e.g., M1) showed decrements in Ca;{2+} clearance following depolarization (Ca;{2+} Recovery time, Ca;{2+}RT) that were antagonized by BB. Since it has been postulated that at least part of the loss of cognitive function in aging may be dependent upon a dysregulation in calcium homeostasis (i.e., Ca;{2+}RT), we assessed whether: a) Ca;{2+}RT would be altered in dopamine (DA)- or amyloid beta (Abeta)-exposed cultured primary hippocampal neuronal cells (HNC), and b) BB pre-treatment of the cells would prevent these deficits. Thus, control or BB (0.5 mg/ml)-treated HNC were exposed to DA (0.1 mM, 2 hrs), Abeta(40) (25 microM, 24 hrs), Abeta(42) (25 microM, 24 hrs), and Abeta(25-35) (25 microM, 24 hrs), and Ca;{2+}RT following KCl-induced depolarization assessed. Ca;{2+}RT was assessed as the % of HNC showing recovery to 50%-70% of control at 5, 10, or 15 min after depolarization. Results indicated that DA significantly lowered Ca;{2+}RT in the HNC at all time points examined after depolarization. However, BB treatment selectively prevented these declines in Ca;{2+}RT. In the case of Abeta, the greatest effects on Ca;{2+}RT were seen when the hippocampal cells were Abeta(42)-treated. These effects were antagonized by BB treatment. Abeta(40) produced fewer deficits on Ca;{2+}RT than those seen when the HNC were pre-treated with either A;{2+}(42) or A;{2+}(25-35), but BB was relatively ineffective in antagonizing the deficits in Ca;{2+}RT produced by A;{2+}(40) or A;{2+}(25-35). Additional analyses indicated that BBs may be exerting their protective effects in the hippocampal cells by altering levels of phosphorylated MAPK, PKCgamma, and phosphorylated CREB. Therefore it appears that at least part of the protective effect of BBs may involve alterations in stress signaling.

Cognitive function, P3a/P3b brain potentials, and cortical thickness in aging.

The purpose of the study was to assess the relationship between the P3a/P3b brain potentials, cortical thickness, and cognitive function in aging. Thirty-five younger and 37 older healthy participants completed a visual three-stimuli oddball ERP (event-related potential)-paradigm, a battery of neuropsychological tests, and MRI scans. Groups with short vs. long latency, and low vs. high amplitude, were compared on a point by point basis across the entire cortical mantle. In the young, thickness was only weakly related to P3. In the elderly, P3a amplitude effects were found in parietal areas, the temporoparietal junction, and parts of the posterior cingulate cortex. P3b latency was especially related to cortical thickness in large frontal regions. Path models with the whole sample pooled together were constructed, demonstrating that cortical thickness in the temporoparietal cortex predicted P3a amplitude, which in turn predicted executive function, and that thickness in orbitofrontal cortex predicted P3b latency, which in turn predicted fluid function. When age was included in the model, the relationship between P3 and cognitive function vanished, while the relationship between regional cortical thickness and P3 remained. It is concluded that thickness in specific cortical areas correlates with scalp recorded P3a/P3b in elderly, and that these relationships differentially mediate higher cognitive function.

Surprising Lack of Sex Differences in Normal Cognitive Aging in Twins

Sex differences in the etiology of normal cognitive functioning in aging remain largely unexplored. We conducted an investigation of genetic and environmental contributions to sex differences in level of cognitive performance and rate of decline in the Swedish Adoption/Twin Study of Aging (SATSA) (Finkel & Pedersen, 2004) data set. Behavioral genetic parameterizations of a latent growth curve model were fit to longitudinal data on 11 cognitive measures. Seven hundred and ninety-eight non-demented individuals had cognitive data across four waves of measurement covering 13 years. Participants ranged in age from 44 to 88 at first testing wave; 60% were female. Results indicated sex differences in mean performance for five cognitive measures and in rates of decline for Information and Card Rotations. Only Synonyms demonstrated sex differences in genetic and environmental contributions to mean performance: heritability was higher in men than women. Despite differential longevity and susceptibility to disease, there are no consistent indications that men and women show different patterns of cognitive aging.

WITHDRAWN: Dehydroepiandrosterone (DHEA) supplementation for cognitive function.

In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects. The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist.Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

The impact of recurrent hypoglycemia on cognitive function in aging

The decline in cognitive function, especially on challenging tasks, associated with aging is well known and relatively well-characterised. Recent evidence has provided strong support for the view that reduced ability to provide and regulate fuel supply, i.e., glucose, to the aged brain is a major cause of such decline. Inability to regulate glucose also defines diabetes, and both diabetes and the recurrent hypoglycemia seen in intensively insulin-treated diabetic patients also affect cognition. Recent data on the interaction between such recurrent hypoglycemia and aging in modulating cognition is reviewed, and the insights gained into mechanisms of age-related cognitive decline discussed.

Parkinsonian signs and cognitive function in old age

Studies have shown that parkinsonian signs are related to cognitive function in aging. What remains unclear is whether this association is stronger for some cognitive domains than it is for others, and precisely how much variability in global and specific cognitive functions is explained by the motor signs. We examined the associations between four parkinsonian signs (gait, rigidity, bradykinesia, tremor) and five cognitive domains (episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability) in a large cohort of older persons who were free of Parkinson's disease and dementia and were participating in the Rush Memory and Aging Project. In a series of regression equations that controlled for age, sex, and education, higher levels of three signs (gait, rigidity, and bradykinesia) were related to lower levels of cognitive function, but they accounted for less than 5% of the variance in most measures. The results did not change when the presence of depressive symptoms, diabetes, and hypertension were added to the models. The cross-sectional association between parkinsonian signs and cognitive function did not vary substantially across specific cognitive domains or specific cognitive tests. The results suggest that parkinsonian signs have a modest, but statistically reliable, association with level of cognitive function in old age.

Physical activity and cognitive functioning in aging

Aging is associated with decline in a multitude of cognitive processes and brain functions. A growing body of literature suggests that decline in cognitive functioning of older adults can be reduced through memory training and physical activity. The purpose of this article was to examine the hypothesis that physical activity enhances cognitive functioning, to summarize the cross-sectional and intervention research in this area, and to discuss potential mechanisms underlying the cognitive improvement. Finally, some suggestions for future research are outlined.

P.2.014 The effect of DHEA administrationon extrapyramidal symptoms in schizophrenia: A randomized double blind placebo controlled trial

Brain-derived neurotrophic factor (BDNF) is a neurotrophin abundantly expressed in several areas of the central nervous system (CNS) and is known to induce a lasting potentiation of synaptic efficacy, to enhance specific learning and memory processes. BDNF is one of the key molecules modulating brain plasticity and it affects cognitive deficit associated with aging and neurodegenerative disease. Several studies have shown an altered BDNF production and secretion in a variety of neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases but also in mood disorders like depression, eating disorders and schizophrenia. Plasma BDNF is also a biomarker of impaired memory and general cognitive function in aging women.Gonadal steroids are involved in the regulation of several CNS processes, specifically mood, affective and cognitive functions during fertile life and reproductive aging. These observations lead many scientists to investigate a putative co-regulation between BDNF and gonadal and/or adrenal steroids and their relationship with gender difference in the incidence of mental diseases.This overview aims to summarize the current knowledge on the correlation between BDNF expression/function and both gonadal (progesterone, estrogens, and testosterone) and adrenal hormones (mainly cortisol and dehydroepiandrosterone (DHEA)) with relevance in clinical application.

Multiple cognitive deficits during the transition to Alzheimer's disease.

The literature on cognitive markers in preclinical AD is reviewed. The findings demonstrate that impairment in multiple cognitive domains is typically observed several years before clinical diagnosis. Measures of executive functioning, episodic memory and perceptual speed appear to be most effective at identifying at-risk individuals. The fact that these cognitive domains are most implicated in normal cognitive aging suggests that the cognitive deficit observed preclinically is not qualitatively different from that observed in normal aging. The degree of cognitive impairment prior to the diagnosis of Alzheimer's disease (AD) appears to generalize relatively well across major study characteristics, including sample ascertainment procedures, age and cognitive status of participants, as well as time to diagnosis of dementia. In episodic memory, there is evidence that the size of the preclinical deficit increases with increasing cognitive demands. The global cognitive impairment observed is highly consistent with observations that multiple brain structures and functions are affected long before the diagnosis of AD. However, there is substantial overlap in the distribution of cognitive scores between those who will and those who will not be diagnosed with AD, hence limiting the clinical utility of cognitive markers for early identification of cases. Future research should consider combining cognitive indicators with other types of markers (i.e. social, somatic, genetic, brain-based) in order to increase prediction accuracy.

Elevated Postsynaptic [Ca2+]iand L-Type Calcium Channel Activity in Aged Hippocampal Neurons: Relationship to Impaired Synaptic Plasticity

Considerable evidence supports a Ca(2+) dysregulation hypothesis of brain aging and Alzheimer's disease. However, it is still not known whether (1) intracellular [Ca(2+)](i) is altered in aged brain neurons during synaptically activated neuronal activity; (2) altered [Ca(2+)](i) is directly correlated with impaired neuronal plasticity; or (3) the previously observed age-related increase in L-type voltage-sensitive Ca(2+) channel (L-VSCC) density in hippocampal neurons is sufficient to impair synaptic plasticity. Here, we used confocal microscopy to image [Ca(2+)](i) in single CA1 neurons in hippocampal slices of young-adult and aged rats during repetitive synaptic activation. Simultaneously, we recorded intracellular EPSP frequency facilitation (FF), a form of short-term synaptic plasticity that is impaired with aging and inversely correlated with cognitive function. Resting [Ca(2+)](i) did not differ clearly with age. Greater elevation of somatic [Ca(2+)](i) and greater depression of FF developed in aged neurons during 20 sec trains of 7 Hz synaptic activation, but only if the activation triggered repetitive action potentials for several seconds. Elevated [Ca(2+)](i) and FF also were negatively correlated in individual aged neurons. In addition, the selective L-VSCC agonist Bay K8644 increased the afterhyperpolarization and mimicked the depressive effects of aging on FF in young-adult neurons. Thus, during physiologically relevant firing patterns in aging neurons, postsynaptic Ca(2+) elevation is closely associated with altered neuronal plasticity. Moreover, selectively increasing postsynaptic L-VSCC activity, as occurs in aging, negatively regulated a form of short-term plasticity that enhances synaptic throughput. Together, the results elucidate novel processes that may contribute to impaired cognitive function in aging.

Dehydroepiandrosterone (DHEA) supplementation for cognitive function .

In view of the theoretical rationale for beneficial effects of DHEA and DHEAS on cognitive function in ageing and dementia, we have undertaken a thorough investigation of well-conducted studies in this area. This will provide a basis for confirmation of any effect of DHEA/S administration in humans in properly controlled trials. The review will also provide a scientific basis for effective dosage, acceptable route and duration of administration, and side effect profiles. This review is especially pertinent at this time as DHEA is currently being sold in large quantities in health food stores, particularly in the USA. In some cases the recommended dose is different for men and women (50mg/day for men and 25mg/day for women) and the basis for this recommendation needs to be explored. To establish whether administration of DHEA, or its sulphate, DHEAS, improves cognitive function or reduces the rate of decline of cognitive function in normal older adults or in individuals with dementia. Relevant electronic databases, journals, personal communications and conference abstracts were searched for randomised controlled trials investigating the effects of DHEA/S on cognition in older adults. All relevant randomised controlled trials of DHEA/S were considered for inclusion in the review. Data for the specified outcomes were independently extracted by two reviewers (FAH & JvN) and cross-checked. Any discrepancies were discussed and resolved. No data pooling was undertaken owing to the lack of availability of the relevant statistics. There are four included studies, three cognition in normal older people, and Barnhart 1999 in perimenopausal women with decreased well-being. There were no studies in dementia. There were a few significant findings. Wolf 1997 found significant improvement following DHEA compared with placebo in both immediate recall (MD 0.8, 95% CI 0.16, 1.44) and delayed recall (MD 0.9, 95% CI 0.09, 1.71) of a visual memory test in women, estimated in a crossover trial after 2 weeks of treatment with each of DHEA and placebo. However there was no significant improvement in men, nor a significant effect on a verbal memory test. There was also no significant effect on four other cognitive tests. Wolf 1998 (2) found that placebo group performance deteriorated significantly on a test of selective attention following a psychosocial stressor (p<0.05), while deterioration was not evident in the DHEA group (p=0.85) after two weeks of treatment. However, when compared to placebo, DHEA produced a significant impairment on a visual memory test (p<0.01) following the stressor. No significant effect was found on a third cognitive task. Effects were not found on tasks when administered in the absence of a stressor. Barnhart 1999 employed three cognitive measures and found no significant effect of DHEA compared with placebo at 3 months. Findings to date suggest that DHEA replacement seems to be well tolerated with an absence of significant side-effects. The data offer no support at present for an improvement in memory or other aspects of cognitive function following DHEA treatment in normal older people. In view of the growing public enthusiasm for DHEA supplementation, particularly in the USA, and the possibility that any neuroprotective effect of DHEA/S may only be evident in the long term, there is a need to undertake high quality trials in which the duration of DHEA treatment is longer than one year, and the number of participants is large enough to detect effects if they exist. Recently, trials of DHEA supplementation in Alzheimer's Disease (USA), post-menopausal women (USA), normal older men (UK), and a one-year trial in normal older men and women (France) have been completed. As soon as the results are available these studies will be included in the review.

Apolipoprotein E, amyloid beta 40 and 42, and cognitive function in aging and Alzheimer's disease

Apolipoprotein E, amyloid beta 40 and 42, and cognitive function in aging and Alzheimer's disease