Neuropeptide dietary supplement N-PEP-12 enhances cognitive function and activates brain bioelectrical activity in healthy elderly subjects.

N-PEP-12 is a dietary supplement consisting of neuropeptides and amino acids. In animal experiments, the compound has been shown to enhance cognitive function and reduce neurodegenerative events associated with aging. In this study, we investigated the effects of a single oral dose of N-PEP-12 (180 mg) on brain bioelectrical activity and cognitive performance in healthy elderly subjects. N-PEP-12 induced a significant (p < 0.05) increase in relative alpha-activity power 6 h after administration. This enhancement was accompanied by a generalized decrease in slow Delta-activity. Significant improvement in memory performance subtests was also seen 6 h after N-PEP-12 administration in some but not in all tests. Taken together, these data suggest that N-PEP-12 might be a reliable dietary supplement to be investigated for improving and, perhaps, maintaining brain function among healthy older adults.

Raloxifene hydrochloride, a selective estrogen receptor modulator: safety assessment of effects on cognitive function and mood in postmenopausal women.

Raloxifene hydrochloride (HCl) is a selective estrogen receptor modulator with estrogen agonist effects on bone and lipid metabolism and estrogen antagonist effects on reproductive tissues. Animal studies suggest that raloxifene may affect brain function as well, although the effects of raloxifene on the human brain remain to be established. This paper presents an early safety assessment of raloxifene effects on cognition and mood in postmenopausal women participating in a randomized, double-blind osteoporosis treatment trial. Psychometric test batteries were administered to postmenopausal women at baseline and 1, 6, and 12 months after initiating treatment with raloxifene (60 and 120 mg/day). The Memory Assessment Clinics (MAC) battery and Walter Reed Performance Assessment Battery (PAB) were used to assess multiple and independent aspects of cognitive function, while mood was assessed with the Geriatric Depression Scale (GDS). After 12 months of treatment, there were no significant differences between the raloxifene groups and placebo on performance in either the MAC battery or the PAB. The only significant difference observed was a slight increase in performance favoring the raloxifene 120 mg/day group in an assessment of verbal memory on the MAC battery after 1 month of treatment. Scores on the GDS and the self-reported incidence of mood-related events were not different between treatment groups at any of the assessment periods. These data do not suggest that raloxifene impairs cognition or affects mood in postmenopausal women treated for 1 year. Studies to further assess the safety and potential efficacy of raloxifene with respect to cognitive function are ongoing.

Structure of everyday memory in adults with Age-Associated Memory Impairment.

Everyday memory was tested in a group of adults manifesting Age-Associated Memory Impairment; a computerized battery of tests was constructed to simulate memory tasks of daily life. Confirmatory and other structural equation models were estimated for the entire sample of 273 Ss and for 3 age groups. A 4-factor model was found to fit the data well and was invariant across age and gender. After education had been controlled, only the General Recall factor was found to be consistently related to age in both men and women; the other 3 factors--Narrative Memory, Digit Recall, and Visual Memory--were related to age only in men. Confirmatory factor analyses of the everyday memory tests combined with several psychometric memory tests suggested that some of the latter (the Benton Visual Retention Test and Wechsler Memory Scale Hard Paired Associates) load on more than 1 factor of everyday memory, suggesting complex relationships between the 2 types of tests.

Estimated prevalence of age-associated memory impairment derived from standardized tests of memory function.

Recent research on the prevalence of age-associated memory impairment (AAMI) has reflected considerable variability, with estimates ranging from 35% to 98%. This variability is attributed to (a) failure to employ the complete diagnostic criteria for AAMI and (b) failure to consider age as a variable in estimating prevalence. Analysis of published normative data on both standard clinical memory tests and computer-simulated everyday memory tests shows a clear increase in the percentage of persons meeting the AAMI memory performance criterion as a function of age. These data are offered as an upper-bound estimate of the prevalence of AAMI, by age decade.

Memory self-report in Alzheimer's disease and in age-associated memory impairment.

We investigated memory self-report in Alzheimer's disease (AD) and age-associated memory impairment (AAMI). AD and AAMI patients and healthy elderly subjects were administered a self-report memory questionnaire, memory tests, a family-rated memory questionnaire, and a depression scale. The AD group reported worse memory than the control group, but many individual AD subjects reported normal memory. This finding confirms clinical observations that unawareness of memory loss is common in AD but variable across patients. Multiple regression analysis revealed that worse memory self-ratings were associated with greater dementia severity and higher depression scores. In the AAMI group, memory self-ratings were predicted by family ratings of memory ability but not by memory test scores. There was a nonsignificant trend for depression scores to predict memory self-ratings. Finally, level of self-reported memory ability did not differ for AD and AAMI, contradicting clinical lore that memory complaint is a useful diagnostic indicator.

Accelerated forgetting in Alzheimer-type dementia.

Accelerated forgetting of name-face associations and grocery list items within the first hour postpresentation is demonstrated in 80 persons with Alzheimer's disease (AD) compared to 80 control subjects matched on age, education, and gender. Differences in forgetting which exceeded statistical regression effects remained, even when AD and control subjects were matched on rate of acquisition during the learning trials of name-face associations. Results are discussed in relation to the neuropathology of AD, organic amnestic disorders, and methodological factors concerning previous research on forgetting in persons with AD.

Raven's colored progressive matrices: a normative study of a random sample of healthy adults.

Raven's Colored Progressive Matrices Test (RCPM) was administered to 894 normal healthy adults who were randomly selected in six Italian cities and in the Republic of San Marino. Gender, age, and education significantly influenced overall test performance, and performance on different RCPM subsets. Findings from this large random sample provide demographic corrections to test scores for use in clinical practice.

Learning, forgetting, and retrieval of everyday material across the adult life span.

Levels and rates of acquisition and amounts of forgetting of name-face associations and grocery list items were assessed in a sample of 1,921 normal participants that was divided into five age groups (i.e., 17-39, 40-49, 50-59, 60-69, and 70+). Retrieval was assessed via the consistent long-term retrieval score (CLTR) from the Grocery List Selective Reminding Test (GLSRT). Substantial linear age-associated declines in level of acquisition were noted for both name-face associations and grocery list items. There was a significant age-related drop in rate of acquisition of name-face associations. Remarkably, very little forgetting occurred over a 40-min delay at any age on either measure. There was a significant linear age-related decline in retrieval efficiency for grocery list items, when variance due to both level of acquisition and retention was removed. The nature of age-associated memory decline and its possible neuroanatomic correlates is discussed.

Do men show more rapid age-associated decline in simulated everyday verbal memory than do women?

Recent magnetic resonance imaging data suggest that men show more rapid age-associated atrophy of the left hemisphere than do women. To investigate whether a similar pattern occurs for functional decline, the authors tested 417 male-female pairs, ages 17-79 years and matched perfectly on age and education, on 3 computer-simulated everyday verbal memory tests: Name-Face Association, First-Last Name Associate Learning, and Grocery List Selective Reminding. Age and gender significantly predicted performance on all 3 tests. By contrast, only 1 of 15 Age x Gender interactions was significant, accounting for merely 1% of the test variance. These data suggest that although gender-based differences in rate of left-hemisphere structural decline may occur with normal aging, these apparently do not translate into differential functional decline in simulated everyday verbal memory.

Traditional and computerized assessment procedures applied to the evaluation of memory change after temporal lobectomy.

After establishing that 40 temporal lobectomy patients (20 right, 20 left) demonstrated the same pattern of memory compromise as has been reported in prior studies, we examined the sensitivity of computerized tests of everyday memory skills to the cognitive change associated with temporal resection. Multiple cognitive deficits occur after left, but not after right, temporal lobectomies. Memory impairment after surgery is not limited to traditionally structured memory tests but is also evident on tasks designed to simulate activities of daily life.

Age and incidental recall for a simulated everyday memory task.

We compared intentional learning on an everyday memory task, associate learning of name-face pairs, with Type II incidental recall of the city of residence for each of the name-face pairs. Performance on intentional and incidental learning was significantly associated with age and performance differences begun as early as the fifth decade. Age was more strongly associated with intentional than with incidental learning, and performance on the single incidental recall trial was most similar to the first trial of the intentional learning task.

Glutamate: its role in learning, memory, and the aging brain.

L-Glutamate is the most abundant of a group of endogenous amino acids in the mammalian central nervous system which presumably function as excitatory neurotransmitters and under abnormal conditions may behave as neurotoxins. As neurotransmitters, these compounds are thought to play an important role in functions of learning and memory. As neurotoxins, they are believed to be involved in the pathogenesis of a variety of neurodegenerative disorders in which cognition is impaired. Moreover, brain structures which are considered anatomical substrata for learning and memory may be particularly vulnerable to the neurotoxic actions of these excitatory amino acids, especially in the elderly who are also the segment of the population most susceptible to impairments of mnemonic function. This paper is a review of data concerning the role of excitatory amino acids in the processes of learning and memory and in the pathogenesis and treatment of disorders thereof.

Factors attenuating the validity of the Geriatric Depression Scale in a dementia population.

OBJECTIVE: The validity of the Geriatric Depression Scale (GDS) in cognitively impaired patients has been questioned. We investigated possible factors (memory loss, dementia severity, unawareness of illness) attenuating the validity of the GDS in patients with dementia. PATIENTS: Eighty-three patients who met research diagnostic criteria for "probable Alzheimer's disease." Subjects with major depressive disorder were excluded. Dementia severity ranged from mild to moderate. SETTING: Outpatient clinics, including institutional settings and private research settings. MEASUREMENTS: Depression--GDS; Hamilton Depression Scale. Memory--Wechsler Memory Scale; Benton Visual Retention Test. Dementia severity--Mini-Mental State Examination. Self-awareness of cognitive deficits--Difference score between a self-report memory questionnaire and an informant-rated memory questionnaire. RESULTS: Multiple regression analysis revealed that Hamilton scores were the major predictor of GDS scores. Memory scores and self-awareness scores were also significant predictors. Dementia severity scores were not a significant predictor. CONCLUSIONS: The GDS is a valid measure of mild-to-moderate depressive symptoms in Alzheimer patients with mild-to-moderate dementia. However, Alzheimer patients who disavow cognitive deficits also tend to disavow depressive symptoms, and the GDS should be used with caution in such patients. Finally, the argument that memory impairment precludes accurate self-report of recent mood is negated by our finding that many patients accurately reported depressive symptoms and that worse memory was associated with more self-reported depressive symptoms.

Cholinergic function in the aged brain: implications for treatment of memory impairments associated with aging.

The cholinergic hypothesis of impaired memory in Alzheimer's disease has stimulated interest in cholinergic function of the brain in relation to the more common and less serious impairments of memory associated with normal (non-disease) aging. Unlike Alzheimer's disease, it is not clear whether normal aging results in a loss of cholinergic innervation to cerebral cortex and hippocampus, but prevailing evidence suggests that certain aspects of brain cholinergic function are diminished with advancing age. Human and animal data on the effects of aging on cholinergic systems of the brain are reviewed and are discussed in connection with the role these effects may play in the etiology and treatment of the learning and memory impairments associated with aging.

Changes in facial recognition memory across the adult life span.

We found significant and similar associations of facial recognition memory performance with age using two different methodologies: signal detection (SD) and delayed nonmatching-to-sample (DNM). These data demonstrate that previously reported associations between age and facial recognition memory performance were not specific to method of assessment, and that significant declines are seen as early as 50 years of age.

Everyday memory performance across the life span: effects of age and noncognitive individual differences.

Gerontologists have long been concerned with the impact of individual-difference factors on memory. This study used a large sample (N = 2,495) of adult volunteers aged 18 to 90 years to determine if a set of individual-difference variables--vocabulary, education, depression, gender, marital status, and employment status--mediates the effects of aging on a wide range of laboratory-analogue tests of everyday memory. The data indicated that age was consistently the most significant predictor of memory performance, followed by vocabulary and gender. Vocabulary totally mediated age effects on a prose memory measure, and partial mediation of aging effects--primarily by vocabulary and gender--was observed on 5 other memory tests. These data suggest that when health samples of volunteers serve as research subjects, these individual differences can affect some memory test scores, but age remains the best overall predictor of memory performance.

Assessment of memory complaint in age-associated memory impairment: the MAC-Q.

Few brief self-report memory questionnaires are available, and non has been well validated. We designed a brief questionnaire, the MAC-Q, to assess age-related memory decline. Validity and reliability of the MAC-Q were assessed in 232 subjects meeting diagnostic criteria for age-associated memory impairment (AAMI). Concurrent validity of the MAC-Q was supported by a significant correlation (r = .41, p < .001) with a lengthy, well-validated memory questionnaire. Multiple regression analysis indicated that memory test scores were significant predictors of MAC-Q scores. MAC-Q scores were not predicted by Hamilton Depression Scale scores, suggesting that memory complaint in AAMI is not related to affective status. Internal consistency and test-retest reliability of the MAC-Q were satisfactory. Our data support the validity and reliability of the MAC-Q, a new brief memory questionnaire. The MAC-Q is of particular relevance to the assessment of AAMI, but should also prove useful in any clinical or research setting requiring a brief index of memory complaint.

Normative data on a self-rating scale for evaluating memory in everyday life.

Normative data are provided on 1,106 subjects who were administered a memory self-rating scale. This scale includes 21 ability-to-remember items yielding 5 factors, 24 items assessing frequency-of-occurrence of memory failures yielding five factors, and four global rating items assessing overall comparison to others, comparison to the best one's memory has been, speed of recall, and concern or worry over memory function. Test-retest reliabilities of the various self-rating factors exceeded .80. Research and clinical applications are discussed.