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PubMed2002

Cellular and systems reconsolidation in the hippocampus.

Cellular theories of memory consolidation posit that new memories require new protein synthesis in order to be stored. Systems consolidation theories posit that the hippocampus has a time-limited role in memory storage, after which the memory is independent of the hippocampus. Here, we show that intra-hippocampal infusions of the protein synthesis inhibitor anisomycin caused amnesia for a consolidated hippocampal-dependent contextual fear memory, but only if the memory was reactivated prior to infusion. The effect occurred even if reactivation was delayed for 45 days after training, a time when contextual memory is independent of the hippocampus. Indeed, reactivation of a hippocampus-independent memory caused the trace to again become hippocampus dependent, but only for 2 days rather than for weeks. Thus, hippocampal memories can undergo reconsolidation at both the cellular and systems levels.

Amnesia, Retrograde↗

PubMed2003

Age-related memory impairment. Is the cure worse than the disease?

Aging impairs multiple memory systems. The neurochemical substrates of normal memory differ between memory systems. In this issue of Neuron, Ramos et al. find that activation of protein kinase A, which has been reported to improve hippocampal-dependent spatial memory in aged animals, has the opposite effect on prefrontal cortex-dependent working memory in aged animals.

Animals↗

PubMed2001

Temporal order and spatial memory in schizophrenia: a parametric study.

Spatial working memory has been shown to be impaired in schizophrenia. In contrast, memory for temporal order has been poorly studied in patients with schizophrenia. The aim of this study was to compare and to further characterize spatial working memory and sequence reproduction deficits in patients with schizophrenia under stable medication by manipulating cues (pattern versus sequence), delay, set-size and response type in various recall and recognition tasks. This allowed us to dissociate processes as encoding, retention and retrieval and to compare the performance of patients with schizophrenia to the performance of patients with prefrontal lesions, who have been previously tested in the same tasks. Our results show that increase of the set-size and of the delay decreased performance of both groups, and that these factors had larger detrimental effects in patients with schizophrenia than in controls. Furthermore, comparison between tasks revealed retention and retrieval deficits in schizophrenia. Finally, patients with schizophrenia showed impairments not only in recall but also in sequence recognition tasks with delay. This is in contrast to patients with prefrontal lesions, who have previously been shown to have intact recognition of sequences after a delay. These results suggest that the working memory deficit in schizophrenia cannot be restricted to a prefrontal dysfunction.

Adult↗

PubMed2000

Changes in memory processing with age.

Over the years, a large body of literature has shown that humans display losses in memory with age, but that not all types of memory are affected equally. Similarly, recent evidence from functional neuroimaging experiments has revealed that, depending on the task, older adults can display greater or lesser activity in task-relevant brain areas compared with younger adults. Recent behavioral and neurophysiological experiments are furthering our understanding of the effects of aging on cognition. It appears that some brain changes seen with age may be compensatory.

Adaptation, Physiological↗

PubMed2003

Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury.

The present study is designed to investigate the effect of dietary flavanoid rutin, micronutrient selenium and garlic oil on ischaemia and reperfusion-induced cerebral injury. Global cerebral ischaemia was induced by occluding right and left common carotid arteries for 10min followed by reperfusion for 24h. Cerebral infarct size was estimated using triphenyltetrazolium chloride staining. Elevated plus maze was employed to estimate short-term memory. Degree of motor incoordination was evaluated using inclined beam-walking test and lateral push test. Mitochondrial thiobarbituric acid reactive substances (TBARS) assay was employed as an index of oxidative stress. Global cerebral ischaemia followed by reperfusion produced a significant impairment in short-term memory and motor coordination and produced a notable increase in mitochondrial TBARS. Administration of rutin and garlic oil before global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. Administration of sodium selenite either before or after global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. The protective effect of rutin, sodium selenite and garlic oil was accompanied by a marked decrease in mitochondrial TBARS. On the basis of these results, it may be suggested that rutin and garlic oil administrated before cerebral ischaemia may scavenge reactive oxygen species and consequently attenuate global cerebral ischaemia and reperfusion-induced cerebral injury. Sodium selenite administrated before and after cerebral ischaemia may be neuroprotective due to its antioxidant effect.

Allyl Compounds↗

PubMed2003

Prevalence of dementia in three ethnic groups: the South Florida program on aging and health.

To determine the prevalence of cognitive impairment and dementia in a multi-ethnic community, we examined a population sample of 2,759 elderly (65 years of age and older) African American, Hispanic-Cuban and white non-Hispanic men and women of Dade County, Florida. The Short Portable Mental Status Questionnaire (SPMSQ) was used as a screening test. The prevalence of cognitive impairment for African American men was 17.0% and women 16.7%; Cuban men 9.4% and women 11.4%; and white non-Hispanic men 9.0% and women 8.5%. Participants with cognitive impairment were referred to two Memory Disorder Clinics for diagnosis of dementia/Alzheimer's disease (AD). SPMSQ cutpoints took account of race and education. The prevalence of dementia/AD was adjusted for sensitivity and specificity of the SPMSQ in each sex/ethnic group. The prevalence of dementia among African American men (20.9%) was twice that among white non-Hispanic men (11.6%). White non-Hispanic and Cuban women had a similar prevalence of dementia (12.1% vs. 12.9%). Low SPMSQ specificity for Cuban men and African American women gave unstable dementia prevalence estimates. More than two thirds of all dementia cases had AD, and among white non-Hispanics, women had double the prevalence of AD among men (10.9% vs. 5.4%). The prevalence of AD among African American men was more than two and a half times greater than the prevalence among white non-Hispanic men (14.4% vs. 5.4%). Age (p = 0.001), family history of AD (p = 0.02) and African American (p = 0.0001) or Cuban (p = 0.006) ethnic group were directly and independently associated with the prevalence of AD.

Black or African American↗

PubMed1999

Detecting drug effects on short-term memory function using a combined delayed matching and non-matching to position task.

Operant delayed non-matching-to-position (DNMTP) and delayed matching-to-position (DMTP) have become standard techniques to investigate drug effects on short-term memory function in rats. However, these two tasks are normally conducted in isolation. Using two standard drugs, the 5HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and the muscarinic antagonist scopolamine, this study looked at a two-choice operant task that essentially involved a mixed DNMTP/DMTP paradigm. Thus, DNMTP trials were interspersed with DMTP trials in a random sequence for the duration of a session. 8-OH-DPAT (0.03 mg/kg) slightly but significantly improved response accuracy in a delay-dependent fashion during DMTP but not DNMTP trials. The highest dose of 8-OH-DPAT (0.1 mg/kg) impaired accuracy during DNMTP trials independent of delay and had no significant effect during DMTP trials. Scopolamine (0.1 mg/kg) produced delay-dependent deficits in accuracy during DMTP trials but delay-independent impairments during DNMTP trials. Because both 8-OH-DPAT and scopolamine produced delay-dependent effects with DMTP trials types and either had no effect (8-OH-DPAT) or produced delay-independent impairments (scopolamine) during DNMTP trials types, it is suggested that DMTP trials had a greater dependence on short-term working memory function than DNMTP trials that probably relied more on positional (mediating) strategies for solving the task. Therefore, we believe that this mixed DNMTP/DMTP task offers greater potential for more reliable and discerning interpretation of data regarding short-term memory function in rodents than either of the paradigms performed in isolation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1975

Pattern of intellectual impairment in Huntington's chorea.

Cognitive function was evaluated in 11 patients with Huntington's chorea, using eight subtests of the WAIS, and their performance was compared with that previously reported for a normal aged population. The pattern of impairment was similar in the two groups. Tests of immediate memory were given to nine of these patients, and to 10 healthy but aged subjects. In both groups, there was a significant correlation between the performance of individuals in these tests and their IQ, suggesting that the choreic patients had no selective impairment of immediate memory. The clinical and psychological records of the 11 patients revealed no evidence of focal deficits, and the majority of patients were fully orientated and retained insight to their condition. These observations are discussed in relation to the pattern of intellectual impairment seen in other presenile dementias.

Adult↗

PubMed1999

Verbal working memory and sentence comprehension.

This target article discusses the verbal working memory system used in sentence comprehension. We review the concept of working memory as a short-duration system in which small amounts of information are simultaneously stored and manipulated in the service of accomplishing a task. We summarize the argument that syntactic processing in sentence comprehension requires such a storage and computational system. We then ask whether the working memory system used in syntactic processing is the same as that used in verbally mediated tasks that involve conscious controlled processing. Evidence is brought to bear from various sources: the relationship between individual differences in working memory and individual differences in the efficiency of syntactic processing; the effect of concurrent verbal memory load on syntactic processing; and syntactic processing in patients with poor short-term memory, patients with poor working memory, and patients with aphasia. Experimental results from these normal subjects and patients with various brain lesions converge on the conclusion that there is a specialization in the verbal working memory system for assigning the syntactic structure of a sentence and using that structure in determining sentence meaning that is separate from the working memory system underlying the use of sentence meaning to accomplish other functions. We present a theory of the divisions of the verbal working memory system and suggestions regarding its neural basis.

Cognition↗

PubMed1978

Computerized assessment of memory performance in dementia.

Memory deficits in demented patients were studied by applying a computerized system to titrate individual memory performance. Two delayed matching to sample tasks were used. ABA1 involved random visual shapes used as a measure of visual memory. ABA2 involved nonsense syllable trigrams used as a measure of verbal memory. A Human Test System panel with a display screen was utilized. This screen was a rear view projection window divided into four independent 3 X 2 sections arranged in a 2 X 2 matrix. The sample stimulus appeared on the upper left window for one second. The delay interval between stimulus sample and choices varied by 7 seconds dependent upon patient performance per trial. Also utilized was a color distractor task. Task parameters, data acquisition, retrieval, and graphic print-outs were all computerized. Individual titration levels reflected the severity of neurological impairment. Computerized assessment enabled subtle changes in memory performance to be readily identified. Implications for use of the system as a screening device in the assessment of mental changes in the elderly are apparent.

Aged↗

PubMed1986

Neurological abnormalities associated with severity of dementia in Alzheimer's disease.

Abnormal findings on neurological examination were evaluated in 165 patients with a clinical diagnosis of Alzheimer's disease who attended a memory disorders clinic. Severity of dementia was measured by the Blessed Dementia Scale, and associations of abnormalities with dementia severity were evaluated using logistic regression. Presence of aphasia, apraxia, and primitive reflexes on neurological examination were strongly associated with severity, and weak associations were observed for abnormalities of muscle tone and gait. Among these associated neurological features, only aphasia and apraxia were present in mildly demented cases with sufficient frequency to suggest utility as diagnostic signs early in the course of the disease.

Alzheimer Disease↗

PubMed2001

The Behavior Problems Checklist-Spanish: a preliminary study of a new scale for the assessment of depressive symptoms and disruptive behaviors in Hispanic patients with dementia.

Few instruments are available with which to measure behavioral and psychological signs and symptoms in Hispanic patients with dementia. Therefore, the aim of the current study was to develop and evaluate a 17-item scale adapted from the Revised Memory and Behavior Problems Checklist. This measure, the Behavior Problems Checklist-Spanish (BPC-S), assesses caregiver-reported symptoms of depression and disruption in patients with dementia. The sample for this study comprised 27 Spanish-speaking Hispanic patients and their family caregivers evaluated at a university-affiliated memory disorders center. All patients met diagnostic criteria for possible or probable Alzheimer's disease as set forth by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association. Satisfactory convergent validity, discriminant validity, and internal consistency reliability were demonstrated for the Depression and Disruption subscales of the BPC-S. Both of these neuropsychiatric disturbances were related to heightened levels of caregiver burden. The results of this preliminary study suggest the BPC-S is a brief, psychometrically sound caregiver-report instrument to assess symptoms of mood disturbance and behavioral disruption in Hispanic patients with dementia. This instrument may have utility for both clinical and research purposes.

Aged↗

PubMed2004

Apolipoprotein E polymorphism and age of onset for Alzheimer's disease in a bi-ethnic sample.

OBJECTIVE: This study examined the association between the Apolipoprotein-E epsilon4 allele (APOE epsilon4) and age of disease onset in a bi-ethnic sample of community dwelling Alzheimer's disease (AD) patients. DESIGN: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic. SUBJECTS: A clinic-based cohort of white non-Hispanic (WNH; n=601) and white Hispanic (WH; n = 359) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria. MEASURES: Global cognitive functioning of the subjects was evaluated using the Mini-mental State Exam. The age of onset of AD was calculated from the patient's current age minus the reported duration of disease obtained from a knowledgeable family member. RESULTS: A significant relationship was discovered between APOE epsilon4 and age of onset for WNH, with lower ages of onset among patients carrying the epsilon4/epsilon4 and epsilon3/epsilon4 genotypes in relation to patients with the epsilon3/epsilon3 genotype. The results revealed a more modest effect for APOE genotype in the WH cohort, with a lower age of onset witnessed among epsilon4 positive patients (epsilon2/epsilon4, epsilon3/epsilon4 and epsilon4/epsilon4 genotypes) in comparison to epsilon4 negative patients (epsilon2/epsilon2, epsilon2/epsilon3 and epsilon3/epsilon3 genotypes). CONCLUSION: The association between the epsilon4 allele and earlier age of onset was more pronounced in WNH compared to WH patients, suggesting the impact of APOE polymorphism on clinical phenotype may be different for distinct ethnic groups in the U.S.

Age of Onset↗

PubMed2006

Attentional processes discriminate between patients with mild Alzheimer's disease and cognitively healthy elderly.

BACKGROUND: It is generally accepted that Alzheimer's disease (AD) is mainly characterized by memory disorders. Although recent studies also point to an important role of attention deficits early in the disease, this notion has not yet emerged in clinical practice. Our aim was to assess whether attention, quantified by reaction times, can discriminate between patients with mild AD and controls and therefore contribute to clinical diagnosis. METHODS: In a cross-sectional study, 33 patients with mild AD were matched with cognitively healthy elderly controls for age, gender, educational level and depressive mood. Selective attention (SA), alternating attention (AA) and error-rates were measured by a modified reaction time test. RESULTS: Significant differences between both groups were found for all measures. Logistic regression showed that SA (corrected for individual processing speed) and error-rates could correctly classify subjects with an overall hit ratio of 81%. When attention measures were not corrected for individual processing speed, the overall hit ratio improved to 97%. CONCLUSION: SA and AA deteriorate in patients with mild AD and these measures can be used to discriminate between patients and matched controls, independently of depressive mood.

Aged↗

PubMed2005

Recall discriminability: utility of a new CVLT-II measure in the differential diagnosis of dementia.

Memory tests that are in a recall format have almost universally measured accuracy in terms of the number of target items reported by the examinee. However, this traditional scoring method can, in certain cases, result in artificially inflated memory accuracy scores. That is, just as a "yes" response bias and high false-positive rate on recognition testing can artificially inflate a patient's hit rate, so, too, a liberal response bias and high intrusion rate on recall testing can artificially inflate a patient's level of target recall. Recognition tests correct for this problem by using a discriminability measure that provides a single score of hit rate relative to false-positive rate; however, recall tests rarely provide a single score of recall accuracy that corrects for intrusion rate. In the present study, we examined the utility of a new recall discriminability measure that analyzes target recall relative to intrusion rate. Patients with Alzheimer's disease (AD) or Huntington's disease (HD) were administered the CVLT-II, which provides both the traditional measure of target recall and a new measure of recall discriminability. The results indicate that the new recall discriminability measure was superior to the traditional level of target recall measure in distinguishing the recall performance of AD and HD patients. Implications of these results for clinical practice and theories of memory disorder in dementia are discussed.

Adult↗

PubMed2006

Working memory deficits in multiple sclerosis: comparison between the n-back task and the Paced Auditory Serial Addition Test.

Working memory (WM) deficits are common in multiple sclerosis (MS). The Paced Auditory Serial Addition Test (PASAT) is used frequently to measure WM in clinical settings. The n-back paradigm is used often in experimental studies of WM. One unique component of the n-back task is that it provides a measure of reaction time (RT), an additional behavioral index of processing speed and task difficulty. Despite the use of both tasks to measure WM, their common variance has not been documented. We tested 32 MS patients and 20 controls; performance measures were obtained for both tasks. Compared with controls, MS patients generally had poorer performance on both the PASAT and n-back task. MS patients also had slower RTs on the n-back than controls and showed more slowing than controls as a function of WM load. Correlational analyses showed a high correspondence between performance measures on the PASAT and n-back. Principal components analysis pointed to a common feature of the PASAT, n-back, and specific other neuropsychological measures, that is, processing speed. Although the PASAT and n-back were shown to have a significant amount of shared variance, each test has specific advantages and disadvantages for use in clinical populations.

Acoustic Stimulation↗

PubMed1999

Clinical utility of CERAD neuropsychological battery in elderly Jamaicans.

Information on the clinical utility of neuropsychological tests in non-North-American samples is limited. We examined the diagnostic efficacy of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery in Jamaican men and women age 65 and older. A total of 72 elders were diagnosed as normal and 12 were demented based on history, physical, and neurological examination. Independent of this medical examination, participants were tested with the CERAD battery. Normal controls scored significantly better than dementia patients on all tests in the CERAD battery. A discriminant function found that a combination of Word List Learning Sum Recall and Boston Naming Test correctly classified a total of 81% of the cases (83% of the dements and 81% of the normal controls). This study is the first to demonstrate the clinical utility of the CERAD neuropsychological battery in the differential diagnosis of memory disorders of the aged in a non-North-American sample.

Aged↗

PubMed2001

The pharmacology of human working memory.

Experimental studies conducted primarily on non-human primates have begun to address the anatomical and neurochemical correlates of working memory. There is an associated growing body of experimental literature investigating whether modulating key neurotransmitters can facilitate working memory in humans. This paper reviews evidence that acute modulation of dopamine in particular, but also noradrenaline, acetylcholine and serotonin may influence working-memory performance in humans. Differences in neurochemical specificity with regard to stages of working memory, type of working memory (spatial or non-spatial) and cortical effects are also discussed. This evidence has contributed to neuropharmacological understanding of working memory in humans. The important therapeutic consequences of a better understanding of facilitation of working memory is discussed in reference to schizophrenia, Parkinson's disease and Alzheimer's disease.

Brain Chemistry↗