Levodopa.

Levodopa administered alone or in combination with a peripheral decarboxylase inhibitor is at present the best means available for the control of Parkinson symptoms. It has proved particularly effective in Parkinson's disease and postencephalitic parkinsonism. In these disorders its continued administration for periods that now exceed five years has resulted in sustained therapeutic responses and a significant decrease in mortality rate. Levodopa has been shown to be a safe pharmacologic agent even after long-term usage. However, its potential for inducing side effects makes it essential that patients be carefully screened before use and monitored throughout the period of administration. Though not fully established and lacking FDA approval at this time, levodopa appears to be useful in reversing the symptoms of hepatic encephalopathy and as a diagnostic aid in assessing pituitary disorders as well as uncovering presymptomatic Huntington's chorea.     

Guanidinoacetate administration increases acetylcholinesterase activity in striatum of rats and impairs retention of an inhibitory avoidance task

Guanidinoacetate methyltransferase deficiency (GAMT-deficiency) is an inborn error of metabolism biochemically characterized by accumulation of guanidinoacetate (GAA) and depletion of creatine; the pathogenesis of brain dysfunction in this disorder is not yet established. In the present study we investigated the effect of intrastriatal administration of GAA on acetylcholinesterase (AChE) activity and on memory acquisition, consolidation and retrieval of step-down inhibitory avoidance task in rat. Results showed that GAA significantly increased AChE activity in rat striatum 30 min (50%) and 3 h (25%), but not 6 h after drug administration. GAA impaired test session performance when applied 30 min before training or after training, and before testing sessions, i.e., impaired memory acquisition, consolidation and retrieval. When injected with a 6 hour interval, GAA affected only memory retrieval. Although the mechanisms of action of GAA on AChE activity and on memory are unclear, these findings suggest that the accumulation of GAA found in patients with GAMT-deficiency may be one of the mechanisms involved in neural dysfunction. Further studies are necessary to evaluate these mechanisms.     

Basolateral amygdala noradrenergic influence enables enhancement of memory consolidation induced by hippocampal glucocorticoid receptor activation.

Previously, we reported that bilateral excitotoxic lesions of the basolateral nucleus of the amygdala (BLA) block the enhancing effects of posttraining systemic or intrahippocampal glucocorticoid administration on memory for inhibitory avoidance training. The present study further examined the basis of this permissive influence of the BLA on hippocampal memory functioning. Immediate posttraining unilateral infusions of the specific glucocorticoid receptor agonist RU 28362 (11beta,17beta-dihydroxy-6, 21-dimethyl-17alpha-pregna-4,6-trien-20-yn-3-one; 3.0, 10.0, or 30.0 ng in 0.5 microliter) administered into the dorsal hippocampus of male Sprague-Dawley rats induced dose-dependent enhancement of 48-h inhibitory avoidance retention. Infusions of the beta-adrenoceptor antagonist atenolol (0.5 microgram in 0.2 microliter) into the ipsilateral, but not the contralateral, BLA 10 min prior to training blocked the hippocampal glucocorticoid effects on memory consolidation. Infusions of the muscarinic cholinergic antagonist atropine (0.5 microgram in 0.2 microliter) into either the ipsilateral or contralateral BLA before training did not block the hippocampal glucocorticoid effects. These findings provide further evidence that beta-adrenergic activity in the BLA is essential in enabling glucocorticoid-induced modulation of memory consolidation and are consistent with the hypothesis that the BLA regulates the strength of memory consolidation in other brain structures. The ipsilateral nature of the BLA-hippocampus interaction indicates that BLA influences on hippocampal memory processes are mediated through neural pathways rather than by influences by means of the activation of peripheral stress responses.     

MEMO+: Efficacy,Durability and Effect of Cognitive Training and Psychosocial Intervention in Individuals with Mild Cognitive Impairment

Background/Objectives

There is no consensus on the efficacy of cognitive training in persons with mild cognitive impairment (MCI) because of the paucity of well‐designed randomized controlled trials. The objective was to assess the effect of memory training on the cognitive functioning of persons with MCI and its durability and to evaluate whether this effect generalizes to daily life and whether positive effects could be obtained from psychosocial intervention.

Design

Single‐blind randomized controlled trial.

Setting

Research centers of the Institut Universitaire de Gériatrie de Montréal and Institut Universitaire en Santé Mentale de Québec.

Participants

Older adults meeting criteria for amnestic MCI (N = 145).

Intervention

Participants were randomized to cognitive training, a psychosocial intervention, or a no‐contact control condition. Interventions were provided in small groups in eight 2‐hour sessions.

Measurement

Outcome measures were immediate and delayed composite performance memory scores, psychological health (depression, anxiety, well‐being), and generalization effects of the intervention (strategy use in everyday life, difficulties in complex activities of daily living, memory complaints). Testing was administered before training and immediately, 3 months, and 6 months after training.

Results

Participants in the cognitive training condition improved on the delayed composite memory score and on strategy use in everyday life. Improvement was maintained at the 3‐ and 6‐month follow‐up assessments. Participants in the psychosocial and no‐contact conditions did not show any significant improvement.

Conclusion

Cognitive training improves the memory of persons with amnestic MCI. The effect persists over a 6‐month period, and learned strategies are used in everyday life. Cognitive training is a valid way to promote cognition in MCI.     

Intentional weight loss in overweight and obese individuals and cognitive function: a systematic review and meta‐analysis

High adiposity in middle age is associated with higher dementia risk. The association between weight loss and cognitive function in older adults is still controversial. A meta‐analysis was undertaken to estimate the effectiveness of intentional weight loss on cognitive function in overweight and obese adults. A structured strategy was used to search randomized and non‐randomized studies reporting the effect of intentional and significant weight loss on cognitive function in overweight and obese subjects. Information on study design, age, nutritional status, weight‐loss strategy, weight lost and cognitive testing was extracted. A random‐effect meta‐analysis was conducted to obtain summary effect estimates for memory and attention–executive domains. Twelve studies met inclusion criteria. Seven were randomized trials and the remaining five included a control group. A low‐order significant effect was found for an improvement in cognitive performance with weight loss in memory (effect size 0.13, 95% CI 0.00–0.26, P = 0.04) and attention/executive functioning (effect size 0.14, 95% CI 0.01–0.27, P < 0.001). Studies were heterogeneous in study design, sample selection, weight‐loss intervention and assessment of cognitive function. Weight loss appears to be associated with low‐order improvements in executive/attention functioning and memory in obese but not in overweight individuals.     

The interrelationship of memory functions in a nursing home population

Memory functioning was assessed in a group of thirty nursing home residents to determine the level of functioning and the interrelationship of memory processes and age in this population. Nine different types of memory processes were measured. Results indicated that memory functions in this population were interrelated to a greater extent than in community based elderly populations, yet not to as great an extent as suggested in other more impaired groups. On the other hand, while 21 of the 36 correlations of scores on the tests of memory were statistically significant, the greatest amount of variance accounted for between these test scores was only 55%. This result was interpreted to indicate that the memory functions assessed in this nursing home population were non-unitary in nature. The implications of these findings for memory theory and for the practitioner are discussed.     

Moderate, Long-Term, Alcohol Consumption Potentiates Normal, Age-Related Spatial Memory Deficits in Rats

A modified "Samson" sucrose fading procedure was used to establish voluntary consumption of a 20% ethanol (EtOH) solution in male Sprague-Dawley rats for 18 consecutive months. Intakes were stable over the life span, and corresponded to the moderate to high levels of intake typically observed in human "social" drinkers and alcoholics. The Morris Water Maze (WM), Olton Radial Arm Maze (RM), and a "balance beam" test were used to assess the effects of alcohol and aging on spatial memory and motor function. Aged EtOH-consuming rats (AGED/ALC) demonstrated impaired task acquisition, relative to aged controls (AGED), not reaching criterion performance in either spatial memory task even when given four additional days of training. AGED/ALC rats scored significantly lower on percent correct out of the first eight arm entries, and committed more perseverative errors in the RM. There were no significant performance differences between AGED and AGED/ALC rats on a balance beam test of fine motor coordination and equilibrium, suggesting that deficits observed in the RM and WM were not related to differential motor functioning. These results demonstrated that long-term, moderate, oral self-administration of EtOH, within the range typically consumed by humans, had adverse effects on spatial memory in rats, and that such a pattern of EtOH consumption seemed to exacerbate the decline in cognitive functioning associated with normal aging.     

Effect of acute arecoline, tacrine, and arecoline + tacrine post-training administration on retention in late middle-aged mice

The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. A recent treatment strategy is to combine drugs, particularly cholinergic drugs, to improve their memory enhancing effect. We previously reported that in young, weakly trained mice, the combination of arecoline and tacrine was more effective on a mg/kg basis than either drug administered alone. This was true whether the route of administration was intracerebroventricular, subcutaneous, or oral. These drug treatments have also been found to improve retention in 24-month-old mice. Mice 24 months of age show very poor recall one week after training. Failing memory must develop over time but may only be detected in mice younger than 24 months of age when the retention test interval is substantially longer. We now report that 18-month-old mice trained to avoid footshock in a T-maze show poor retention when tested two months after training and drug administration. Subcutaneous administration of arecoline, tacrine, and arecoline plus tacrine all enhanced retention of 18-month-old mice compared to the saline-injected control. The combination was as effective as the single drug treatments even though 96% less arecoline and 99.7% less tacrine were administered.     

Ethanol Inhibits Spontaneous Activity of Central Nucleus of the Amygdala Neurons but Does Not Impair Retention in the Passive-Avoidance Task

BACKGROUND: Behavioral studies using pharmacological manipulations that increase neuronal activity of the central nucleus of the amygdala (CeA) have implicated the CeA in enhancement of memory modulation. To date, however, there has been a dearth of studies investigating the effect of a drug that decreases CeA activity on memory modulation-a drug that inhibits the neuronal activity of the CeA might be expected to impair memory modulation. To determine whether ethanol inhibits CeA activity and, if so, whether decreased CeA activity is associated with impairment of memory modulation, this study investigated the effect of ethanol on spontaneous single-unit activity of CeA neurons and retention in the passive-avoidance task. METHODS: The effect of ethanol (0.35, 0.75, 1.5, 2.5 g/kg) was determined on spontaneously firing neurons in the CeA in urethane-anesthetized rats by use of standard in vivo single-unit electrophysiological recording techniques. Additionally, the effect of ethanol when administered immediately after training in a standard passive-avoidance task was determined on retention the following day. RESULTS: Ethanol profoundly inhibited spontaneous CeA firing rates in urethane-anesthetized rats at all doses tested. Maximal inhibition was related to dose. Each dose of ethanol significantly inhibited CeA activity within 15 min of administration; within 35 min of administration, 0.75 g/kg of ethanol inhibited CeA activity by 65.2%, and the highest dose (2.5 g/kg) produced nearly complete suppression of CeA activity (81.3%). Although ethanol markedly inhibited CeA activity, these same doses of ethanol failed to impair retention in the passive-avoidance task: 0.35, 0.75, 1.5, and 2.5 g/kg of ethanol, administered immediately after training, failed to alter latency to step-through the following day. CONCLUSIONS: These results show that ethanol profoundly inhibits spontaneous CeA activity and suggest that inhibition of the CeA is not sufficient to impair retention in the passive-avoidance task.     

Pretreatment with Vitamins E and C Prevent the Impairment of Memory Caused by Homocysteine Administration in Rats

Homocystinuria is a metabolic disorder caused by deficiency of cystathione -synthase activity leading to tissue accumulation of homocysteine (Hcy); affected patients present neurological dysfunction. Considering that Hcy induces free radical formation and that memory is impaired by oxidative stress, in the present study we investigated the effect of an acute administration of Hcy on retrieval of step-down inhibitory avoidance in adult rats. The action of vitamins E and C on the effects produced by Hcy was also tested. Adult Wistar rats were pretreated for 1 week with daily i.p. administration of saline (control group) and vitamins E and C (vitamin E 40 mg/kg and vitamin C 100 mg/kg). Hcy (11 mmol/kg) or an equivalent volume of 0.9% saline were administered 1 h before training, 1 h before testing, or immediately after training sessions. Memory was significantly impaired in Hcy-treated group, whereas the rats chronically treated with vitamins E and C had this effect prevented. Present data strongly indicate that Hcy administration impairs memory, an effect probably mediated by oxidative stress since treatment with vitamins E and C prevented amnesia. Assuming the possibility that this might occur in the human condition, reported results may be relevant to explain, at least in part, neurologic dysfunction associated with homocystinuria.     

Effect of Corticotropin and Desglycinamide9-Lysine Vasopressin on Suppression of Memory by Puromycin

The puromycin-induced blockade of expression of maze learning in mice can be prevented by subcutaneous administration of "Purified Cortrophin Gel" up to 3 days prior to training. A similar protective effect was not found when highly purified corticotropin was tested, but was observed after administration of desglycinamide(9)-lysine vasopressin. It appears that pressorpeptides are more potent protective agents than corticotropin when administered subcutaneously, and that vasopressin contamination of the commercial preparation was probably responsible for the protective effects previously reported. These experiments suggest that vasopressin and its congeners modify memory consolidation in such a way that the "expression" of memory becomes insensitive to puromycin.     

Ethanol-Induced Impairments in Spatial Working Memory Are Not Due to Deficits in Learning

BACKGROUND: Acute ethanol administration impairs spatial reference memory and spatial working memory. However, the experimental designs previously used to test spatial working memory fail to make a distinction between the acquisition, or learning, of spatial information and the retention of this information. This study demonstrates that acute ethanol administration impairs spatial working memory, by using a novel experimental design that eliminates the confound between the learning of new spatial information and the testing of this information. METHODS: Long-Evans male rats received three forced trials to the same place for food reward on an elevated radial arm maze. Subjects were then given six free-choice trials in the first acquisition session, followed by a 30-min consolidation period before an additional six free-choice trials were administered-the retention session. Animals were trained to a criterion of five of six correct in both the acquisition and retention over 2 consecutive days. Once criteria were obtained, subjects received either saline or one of three ethanol doses immediately after the acquisition session to investigate whether ethanol alters retention of the learned spatial information. RESULTS: Acute ethanol administration impaired spatial working memory. Rats tested under saline and low-dose ethanol (1.0 g/kg) made significantly more place choices than rats tested under moderate- or high-dose ethanol (1.5 and 2.0 g/kg, respectively). Ethanol produced a temporary impairment in that no significant differences were found when subjects were retrained and retested 24 hr after initial testing. CONCLUSIONS: These results demonstrate that acute ethanol administration impairs spatial working memory and that such a deficit is not contingent on a learning impairment. These results support earlier findings that acute ethanol administration impairs spatial working memory but provide a significant advance by validating a novel training procedure that allows for direct investigation of working memory. Ethanol's impairment of both spatial working memory and spatial reference memory strengthens the similarities between memory impairments due to ethanol administration and memory impairments due to hippocampal lesions.     

Multifactorial memory training with older adults: how to foster maintenance of improved performance

The purpose of this study was to examine the effects of a multifactorial memory training program designed for normal older adults. The multifactorial program involved the training of three components that are critical to memory functioning: recoding operations, attentional functions and relaxation. Two controls groups were used. One control group took part in a general cognitive activation program involving training in problem solving, logical thinking, and visuospatial skills, whereas the other received no training. Three types of tasks were administered to assess potential effects of training: (a) free recall of words within the Buschke selective reminding paradigm, (b) digit span, and (c) the Benton visual retention test. Results indicated that the multifactorial group improved performance following training on several measures of the selective reminding task, and that this improvement was maintained 6 months after completion of training. In addition, the two other groups did not show any improvement of memory performance, and no effects occurred in the digit span and visual retention tasks. This pattern of results suggests that multifactorial training may be an effective way of achieving long-term benefits of training for older people, and that effects of memory training may be relatively task-specific.     

Differential effects of single versus combined cognitive and physical training with older adults: the SimA study in a 5-year perspective

The present study evaluates the effect of cognitive training, of psychoeducational training and of physical training on cognitive functioning, physical functioning, physical health, independent living and well-being in older people. Also the combination of physical training with cognitive training or psychoeducational training, respectively, was evaluated. In contrast to most training studies with older people, training effects were evaluated in a longitudinal perspective over 5 years to analyse long-term-results of cognitive and physical activity on older adults. Training effects were evaluated compared to a no-treatment-control group. Subjects were 375 community residents aged 75–93 years. Up to 5 years after baseline examination, significant training effects were observed in the group exposed to the combined cognitive and physical training. The physical and cognitive status in the participants of this group could be preserved on a higher level compared to baseline, and the participants displayed fewer depressive symptoms than the no-treatment-control group. The results are discussed in the light of recent research regarding the effects of mental and physical activity on brain function in older adults.     

Cognitive Processes in the Elderly:

This article provides information on cognitive processes in the elderly. Topics that are discussed include: remote and recent memory, inferencing, metamemory, affective dimensions, memory training, and problem solving. The purpose of this article is to provide educational gerontologists with a discussion of memory functioning in the elderly. Finally, it is suggested that further research is needed to develop better programs and interventions that incorporate the elderly as an active participant. In this context it is suggested that cognition be viewed as a complex interaction of social, affective and physical factors.     

Parkinson's Disease: A Complete Guide for Patients and Families,by William J. Weiner,Lisa M. Shulman,and Anthony E. Lang

The study aims to evaluate the effects of a physical activity program and a cognitive training program on the long-term memory and selective attention of older adults by comparing the effects of the activities. Twenty-four older adults participated in a physical activity program, 24 in a cognitive training program, and 24 were considered the control group. The physical activity and the cognitive training had a significant effect on long-term memory but no difference between the interventions was found. Only the physical activity improved selective attention. Physical activity programs appear to be the most effective interventions in the promotion of older adults cognitive functions.     

Transfer of a speed of processing intervention to near and far cognitive functions

BACKGROUND: Evidence establishing the potential for modification of cognitive functioning in later adulthood has begun to accumulate. OBJECTIVE: The primary goal of the current study was to evaluate, among older adults, the extent to which standardized speed of processing training transfers to similar and dissimilar speeded cognitive measures as well as to other domains of cognitive functioning. METHODS: Ninety-seven older adults (mean age 73.71 years) were administered a battery of cognitive tests assessing intelligence, memory, attention, verbal fluency, visual-perceptual ability, speed of processing, and functional abilities. Forty-four of the participants received ten 1-hour sessions of speed of processing training. The remainder of participants were in a no-contact control group. Approximately 6 weeks after the pretraining assessment, all participants repeated the same battery of tests. RESULTS: The results revealed training effects for some speed of processing measures, including performance of instrumental activities of daily living, but no transfer to other domains of cognitive functioning. CONCLUSION: Speed of processing training may enhance the speed at which older adults can perform instrumental activities of daily living.     

Impairment of water maze behaviour with ageing is counteracted by maze learning earlier in life but not by physical exercise, food restriction or housing conditions

Spatial learning and memory decline with ageing in humans as well as rats. We examined the influence of different interventions on male Sprague Dawley rats with respect to learning ability and memory at the age of 5, 10 and 18 months. The intervention and control groups were: (RW) voluntary exercise in running wheels, (PW) sedentary, food restricted (by about 25%) to keep them at pair weight with RW, (S1) sedentary, fed ad libitum, (TM) forced training in a treadmill, and, (S4) sedentary, fed ad libitum. The animals in all groups were housed individually except those in group S4, which were housed four in each cage. The ability of learning and memory was determined in the Morris water maze. The results showed a significantly better learning ability when young in comparison with their ability when having grown older. At the age of 18 months, the performance was significantly better in the subgroups which had received training also at the age of 10 months compared to the subgroups receiving their first training. None of the various interventions had any significant effect on these functions. Repeated training seems to be the best intervention with respect to retaining learning ability and memory.     

Cognitive impairment in survivors of out-of-hospital cardiac arrest

Background

The huge importance of rapid provision of care, especially early defibrillation, for survival of out-of-hospital cardiac arrest (OHCA) is well known. This prospective cohort study investigated cognitive functioning of OHCA survivors in relation to the time-related elements of the resuscitation.

Methods

Fifty-seven consecutive survivors, from a cohort of 308 witnessed OHCA patients with ventricular fibrillation as the initial rhythm, underwent extensive neuropsychologic examination, including tests of memory, attention, and executive functioning, 6 months after the resuscitation. Time-related aspects of the resuscitation were collected on scene. Cognitive functioning was studied in relation to the administration of cardiopulmonary resuscitation (CPR) prior to ambulance arrival, and time from collapse to start of CPR, defibrillation, and return of spontaneous circulation (ROSC).

Results

Depending of the test, between 11% and 28% of survivors were cognitively impaired, while 58% scored unimpaired for all tests. Daily life activities were limited in 19% of the patients. Patients who received CPR prior to arrival of the ambulance showed a trend towards overall better cognitive functioning and significant better immediate memory and visuomotor tracking (P = .03 and P < .01). We found a weak correlation between the time to CPR, time to defibrillation, or time to ROSC and cognitive functioning.

Conclusions

The majority of survivors of OHCA with ventricular fibrillation as the initial rhythm are cognitively unimpaired. Long delays to ROSC are compatible with good cognitive outcome. Initiation and cessation of resuscitation efforts should not be based on the duration of circulatory arrest.     

Social recovery and therapeutic mission

Social recovery is defined as restoration to effective social functioning. The Social Recovery Inventory, an instrument derived from role and social exchange theories, is demonstrated as a method of measuring recovery vis-à-vis occupational, familial, and civic functioning. Conditions for social recovery are examined, with discussion of implications for treatment, in-service training, and administration.