Episodic and semantic memory in mild cognitive impairment

Little is known about episodic and semantic memory in the early predementia stage of Alzheimer's disease (AD), which is referred to as mild cognitive impairment (MCI). To explore person knowledge, item recognition and spatial associative memory, we designed the Face Place Test (FPT). A total of 75 subjects participated: 22 patients with early AD, 24 with MCI and 29 matched controls. As predicted, AD patients showed significant deficits in person naming, item recognition and recall of spatial location (placing). Surprisingly, subjects with MCI were also impaired on all components. There was no significant difference between AD and MCI except on the placing component. Analysis of the relationship between semantic (naming) and episodic (recognition and placing) components of the FPT revealed a significant association between the two episodic tasks, but not between episodic and semantic performance. Patients with MCI show deficits of episodic and semantic memory. The extent of impairment suggests dysfunction beyond the medial temporal lobe. The FPT might form the basis of a sensitive early indicator of AD.     

Multidimensional measures of person knowledge and spatial associative learning: can these be applied to the differentiation of Alzheimer's disease from frontotemporal and vascular dementia?

Patients with early stage Alzheimer's disease (AD) show deficits in person knowledge and spatial associative memory. The current investigation examined the ability of impairment in these domains to differentiate AD from other overlapping conditions. In experiment 1, 14 AD patients, 21 vascular dementia (VaD) patients, 11 frontal variant frontotemporal dementia (fvFTD) patients and 41 controls were administered a graded faces test. VaD patients demonstrated a level of impairment comparable to the AD group on both the naming and person identification elements of the task. A mild naming deficit was revealed in the fvFTD group. In experiment 2, 22 AD patients, 23 patients with mild cognitive impairment (MCI), 11 fvFTD patients, 13 semantic dementia (SD) patients, and 23 elderly controls were administered the face-place test, a newly developed task that combines naming of famous faces, item recognition and spatial location. The naming component of the face-place test clearly differentiated SD patients from all dementia groups. All patient groups, except those with fvFTD, showed substantial deficits in the item recognition and spatial components. Consistency analyses indicated a fairly robust association between the two episodic components (item recognition and placing), but not between semantic and episodic elements of the FPT. Person knowledge deficits are, therefore, not specific to AD and the employment of face stimuli may influence the performance of SD patients on tasks of episodic memory.     

Repetition effects in a lexical decision task: the role of episodic memory in the performance of alcoholic Korsakoff patients

To examine the contribution of episodic memory to the successful verbal priming performance of Korsakoff patients, we adapted a lexical decision task which holds constant the processing demands during study and testing. Words and nonwords were repeated at a lag of 0, 1, 3, 8 and 15 items and the decrease in response latency was taken as a measure of priming. In Experiment 1, Korsakoff patients showed repetition priming of a magnitude similar to that obtained by alcoholic controls, even at a lag of 15 intervening items. Experiment 2 explored the effect of word frequency on repetition priming. Korsakoff patients again showed normal priming up to lags of 15, and, as expected, these repetition effects were larger for low frequency than for high frequency words. This outcome was felt to be more consistent with an episodically based familiarity account than with a semantic activation account. Finally, Korsakoff patients were found to be impaired in their ability to use episodic memory in an explicit memory task that used the same material under comparable presentation conditions (Experiment 3). Contemporary processing models of episodic memory are discussed as possible explanations for the successful implicit memory performance by amnesic patients on this task.     

An fMRI study of verbal episodic memory encoding in amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is a high-risk and often prodromal state for the development of Alzheimer's disease (AD) and is characterised by isolated episodic memory impairment. Functional neuroimaging studies in healthy subjects consistently report left prefrontal cortex (PFC) activation during verbal episodic memory encoding. The PFC activation at encoding is related to semantic processing which enhances memory. The purpose of this study was to ascertain whether impaired verbal episodic memory in aMCI is related to PFC dysfunction. Using functional magnetic resonance imaging (fMRI) we compared 10 aMCI patients with 10 elderly controls during verbal encoding. The encoding task was sensitive to the effects of semantic processing. Subsequent recognition was tested to measure encoding success. Behavioural results revealed impaired recognition and a lower false recognition rate for semantically related distracters (lures) in aMCI, which suggest impaired semantic processing at encoding. Both groups activated left hemispheric PFC, insula, premotor cortex and cerebellum, but group comparisons revealed decreased activation in left ventrolateral PFC in the aMCI group. The magnitude of activation in left ventrolateral PFC during encoding was positively correlated with recognition accuracy in the control group but not in the aMCI group. We propose that verbal episodic memory impairment in aMCI is related to PFC dysfunction which affects semantic processing at encoding.     

Impaired word recognition in Alzheimer's disease: The role of age of acquisition

Studies of word production in patients with Alzheimer's disease have identified the age of acquisition of words as an important predictor of retention or loss, with early acquired words remaining accessible for longer than later acquired words. If, as proposed by current theories, effects of age of acquisition reflect the involvement of semantic representations in task performance, then some aspects of word recognition in patients with Alzheimer's disease should also be better for early than later acquired words. We employed a version of the lexical decision task which we term the lexical selection task. This required participants to indicate which of four items on a page was a real word (the three ‘foils’ being orthographically plausible nonwords). Twenty-two patients with probable Alzheimer's disease were compared with an equal number of matched controls. The controls made few errors on the test, demonstrating that the controls were cognitively intact, and that the words were familiar to participants of their age and level of education. The Alzheimer patients were impaired overall, and recognized fewer late than early acquired words correctly. Performance of the Alzheimer patients on the lexical selection task correlated significantly with their scores on the mini mental state examination. Word recognition becomes impaired as Alzheimer's disease progresses, at which point effects of age of acquisition can be observed on the accuracy of performance.     

Using semantic memory to boost 'episodic' recall in a case of developmental amnesia

We report two experiments that investigated factors that might boost 'episodic' recall for Jon, a developmental amnesic whose episodic memory is gravely impaired but whose semantic memory seems relatively normal. Experiment 1 showed that Jon's recall improved following a semantic study task compared with a non-semantic study task, as well as following four repeated study trials compared with only one. Experiment 2 additionally revealed that Jon's recall improved after acting compared with reading action phrases at study, but only if the phrases were well integrated semantically. The results provide some support for the hypothesis that Jon's 'episodic' recall depends on the extent to which he is able to retrieve events using semantic memory.     

Learning and forgetting new names and objects in MCI and AD

We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.     

Preserved recognition in a case of developmental amnesia: implications for the acquisition of semantic memory?

We report the performance on recognition memory tests of Jon, who, despite amnesia from early childhood, has developed normal levels of performance on tests of intelligence, language, and general knowledge. Despite impaired recall, he performed within the normal range on each of six recognition tests, but he appears to lack the recollective phenomenological experience normally associated with episodic memory. His recall of previously unfamiliar newsreel events was impaired, but gained substantially from repetition over a 2-day period. Our results are consistent with the hypothesis that the recollective process of episodic memory is not necessary either for recognition or for the acquisition of semantic knowledge.     

Neuropsychological markers for the diagnosis of Alzheimer's disease

Better knowledge of the preclinical phase of Alzheimer's disease and of the symptomatic pre-dementia stage designated "mild cognitive impairment" will require considerable progress in our understanding of neuropsychological processes. The results of studies suggest that impaired performance in memory tests may serve as a marker for Alzheimer's disease. The best current predictors include stringent tests of episodic memory and recognition tests. The early stages of Alzheimer's disease also seem to involve subtle deficits in semantic memory and attentional processes. Face recognition and denomination seem to be useful tools. Greater accuracy and precision in the transitional zone between healthy aging and the first manifestations of Alzheimer's disease will require work combining data on neuropsychological profiles and neuroimaging.     

Differential decline in word generation from phonemic and semantic categories during the course of Alzheimer's disease: implications for the integrity of semantic memory.

The ability to generate words from phonemic (i.e., words beginning with 'F,' 'A,' and 'S') and semantic (i.e., animals, fruits, and vegetables) categories was assessed longitudinally in patients with Alzheimer's disease (AD; N = 59) and normal controls (NC; N = 59). Patients with AD performed worse than NC participants on both tasks at each of 4 annual evaluations and exhibited greater impairment relative to controls on the semantic-category task than on the phonemic-category task. In addition, the performance of the patients with AD declined over time on both tasks, but the rate of decline was faster on the semantic-category than on the phonemic-category task. Examination of individual responses across the annual evaluations revealed that patients with AD were more consistent than NC participants in failing to generate previously produced semantic-category, but not phonemic-category, items in all years following the 1st year in which the item was not produced. These results are consistent with the notion that patients with AD suffer a gradual deterioration of the organization and content of semantic memory as the disease progresses.     

Nature of personal semantic memory: evidence from Alzheimer's disease

Personal semantic memory is factual knowledge about a person's own past. Although personal semantic memory is assumed to have features of both semantic memory and episodic memory, the relationship to episodic memory and to semantic memory have not been well documented. In patients with Alzheimer's disease, episodic memory, semantic memory, and personal semantic memory are all defective. In this study, the hypothesis that defective personal semantic memory is related to both semantic and episodic memory dysfunction was tested in patients with Alzheimer's disease. Functions of episodic, semantic, and personal semantic memory were examined by using the Wechsler Memory Scale-Revised (WMS-R), subtests of the WAIS-R (Information, Vocabulary, Comprehension and Similarities), and the Family Line Test (FLT) in 62 patients who met the NINCDS/ADRDA criteria for probable Alzheimer's disease. Specific effects of episodic and semantic memory on personal semantic memory were examined by using multiple linear regression analysis with the total score of the FLT as the dependent variable and the WMS-R Delayed Recall weighted sum score and the WAIS-R Semantic Memory score (a composite of standardized scores of the four subtests) as the independent variables. Personal semantic memory function was significantly correlated with both the episodic and semantic memory functions, after controlling age, sex, educational attainment, and severity of dementia. This result supports the hypotheses that personal semantic memory has features of both episodic and semantic memory, and that semantic memory is transformed from episodic memory.     

Differential impact of brain damage on the access mode to memory representations: an information theoretic approach

Different access modes to information stored in long-term memory can lead to different distributions of errors in classification tasks. We have designed a famous faces memory classification task that allows for the extraction of a measure of metric content, an index of the relevance of semantic cues for classification performance. High levels of metric content are indicative of a relatively preferred semantic access mode, while low levels, and similar correct performance, suggest a preferential episodic access mode. Compared with normal controls, the metric content index was increased in patients with Alzheimer's disease (AD), decreased in patients with herpes simplex encephalitis, and unvaried in patients with insult in the prefrontal cortex. Moreover, the metric content index was found to correlate with a measure of the severity of dementia in patients with AD, and to track the progression of the disease. These results underline the role of the medial-temporal lobes and of the temporal cortex, respectively, for the episodic and semantic routes to memory retrieval. Moreover, they confirm the reliability of information theoretic measures for characterizing the structure of the surviving memory representations in memory-impaired patient populations.     

Insights from semantic dementia on the relationship between episodic and semantic memory

An influential theory of long-term memory, in which new episodic learning is dependent upon the integrity of semantic memory, predicts that a double dissociation between episodic and semantic memory is not possible in new learning. Contrary to this view, we found, in two separate experiments, that patients with impaired semantic memory showed relatively preserved performance on tests of recognition memory if the stimuli were perceptually identical between learning and test. A significant effect of semantic memory was only seen when a perceptual manipulation was introduced in the episodic task. To account for these findings, we propose a revision to current models of long-term memory, in which sensory/perceptual information and semantic memory work in concert to support new learning.     

Associative working memory and subsequent episodic memory in Alzheimer's disease

Recent studies indicate deficits in associative working memory in patients with medial-temporal lobe amnesia. However, it is unclear whether these deficits reflect working memory processing or are due to hippocampally mediated long-term memory impairment. We investigated associative working memory in relation to subsequent episodic memory formation in patients with early Alzheimer's disease to examine whether these findings reflect deficits in long-term encoding rather than 'pure' working memory processing. Nineteen patients with Alzheimer's disease and 21 controls performed a working memory task in which objects had to be searched at different locations. The subsequent episodic memory test required participants to reposition objects to their original locations. Patients with Alzheimer's disease were impaired on associative working memory and subsequent episodic memory, but they performed above chance at high-load episodic memory trials. This suggests that when working memory capacity is exceeded, long-term memory compensates.     

Can episodic memory tasks differentiate semantic dementia from Alzheimer's disease?

The performance of two groups of patients with semantic dementia (SD), with predominant right (SDR) and left temporal lobe atrophy (SDL), was contrasted with that of cases with probable Alzheimer's disease (AD) on a range of standard episodic memory tasks. While the SDL group achieved a good score on a composite visual, but not a verbal, episodic memory measure, the AD and SDR groups were equivalently impaired at visual and verbal memory. The SD, but not the AD, groups were, by definition, impaired on simple tests of semantic memory. Standard verbal episodic memory tests, therefore, failed to discriminate patients with SD from those with probable AD and even visual memory tests may result in misclassification of SDR cases.     

Item Priming and Skill Learning in Amnesia

Abstract

This study employed a semantic decision-making task to examine both item priming and skill learning in amnesia, which traditionally have been demonstrated with separate tasks. Fourteen amnesic patients of mixed etiologies and 14 normal control subjects judged whether words represented animate or inanimate objects. One list was presented repeatedly on four continuous blocks of trials, and a new list was presented on the fifth block. For both groups, decision times decreased significantly from Block 1 to Block 5 (indicating skill acquisition) and increased significantly from Block 4 to Block 5 (indicating item-specific learning). The amnesic patients demonstrated a normal rate of skill learning, but a reduced magnitude of item priming. As expected, the amnesics had significantly impaired explicit memory of the implicitly learned items, as measured by recognition accuracy. The results suggest that both implicit and explicit learning of individual items is impaired in amnesia, despite normal semantic skill learning.     

The use of semantic knowledge in Alzheimer's disease: evidence for impairments of attention

The ability to access and use semantic knowledge was examined in 25 patients with Alzheimer's disease (AD) and 31 healthy controls. The AD patients exhibited intact automatic activation of semantic relationships on a semantic priming task. They also made active use of category information on a recognition memory test. However, the patients did not use semantic information to generate expectations on the semantic priming task and were inconsistent in their use of category information on the memory test. It is suggested that attentional deficits underlie the observed impairments and may in fact help explain the patterns of performance across tasks differing widely in their overt cognitive demands.     

Patterns of impairment in autobiographical memory in the degenerative dementias constrain models of memory

Detailed study of the autobiographical memory (ABM) impairments seen in different forms of degenerative dementia, in particular Alzheimer's disease (AD) and semantic dementia (SD) can inform neuropsychological models of memory. A modified ABM questionnaire which allowed more detailed analysis of episodic and semantic ABM was used to study the pattern of deficits in patients with minimal to mild Alzheimer's disease (AD) and in two patients with mild and moderate semantic dementia (SD). The questionnaire tested both cued and free recall. A group of healthy elderly was also tested. AD patients differed from controls in all measures. There was no clear temporal gradient for episodic ABM, but a modest gradient was observed for semantic ABM. The mild SD patient performed at control level for episodic ABM but showed a deficit within the range of the AD patients for semantic ABM except for the most recent life period. In contrast the moderate SD patient was impaired within the range of the AD patients for both episodic and semantic ABM. The evidence for differential impairment of episodic and semantic ABM retrieval in AD and SD is interpreted as supporting the multiple trace model of memory.     

“I remember it as if it were yesterday”: Memory for recent events in patients with semantic dementia

Patients with semantic dementia (SD), who have an incontrovertible deficit in semantic memory, are reported to show good day-to-day memory for recent events; but experimental evidence on their anterograde episodic memory/new learning is somewhat sparse and does not always tell a consistent story. We describe the performance of five SD patients, relative to controls, on (a) a range of semantic memory measures that predictably revealed substantial impairment, and (b) a newly designed naturalistic and incidental episodic task, which included information regarding the items and context of the semantic tasks. As a group, the patients’ episodic memory for these natural events was good, even after a 24-h delay, although case-by-case analysis revealed some heterogeneity in performance. These findings are discussed with regard to the neural substrate of episodic memory and psychological models of long-term memory.     

Reduced levels of specific autobiographical memories in schizophrenia

Autobiographical memory is intrinsically related to the self and personal identity. This study investigated whether both personal episodic memory and semantic memory are impaired in schizophrenia, a disease characterized by an abnormal personal identity. Personal episodic memory and personal semantic memory were investigated in 24 patients with schizophrenia and 24 normal subjects using an autobiographical fluency task and an autobiographical memory inquiry. Autobiographical memory scores and the proportion of specific memories were lower in patients with schizophrenia than in normal subjects. The deficit of personal episodic and semantic memory, as assessed by the autobiographical memory inquiry and the autobiographical fluency task, respectively, was most apparent after the onset of clinical symptoms. Schizophrenia is associated with an impairment of both personal episodic and semantic memory and with a reduction of specific autobiographical memories. Those impairments are consistent with the existence of an abnormal personal identity in patients with schizophrenia.