Memory processing in Alzheimer's disease.

The aim of the present research was to examine automatic and controlled influences on memory processing in patients with Alzheimer's disease using the process-dissociation procedure. In Experiment 1, a source recognition procedure was used, and the patients were found to have significantly reduced estimates of automatic processing and capacity to recognise words seen during the study phase of the procedure. In Experiment 2, a detection of repetition procedure was used to determine whether automatic influences on memory decline as a dementia progressed. The patients showed the expected inability to detect repetition in their responding, but there was no evidence that estimates of automatic processing were predicted by mental status scores or by ratings of the severity of dementia. In the third study, a novel method for estimating parameters in the process-dissociation model, developed from the task used in Experiment 2, was tested in a student sample. In this procedure, participants first produce semantic associates with either high or low relatedness to a list of cue words. These responses are subsequently used in a paired associate learning paradigm to determine independent estimates of recollection and automatic processing. Evidence for the validity of this procedure was found in Experiment 3 and the procedure used to examine memory processing in a sample of persons with dementia (Experiment 4). The patient group was found to have a substantial deficit in controlled recollection and a reduced capacity for automatic memory processing.     

Profile of memory impairment and gray matter loss in amnestic mild cognitive impairment

The present study assessed the patterns of cortical gray matter (GM) loss in patients with amnestic mild cognitive impairment (aMCI) with distinct profiles of memory impairment, i.e. aMCI patients failing on both recall and recognition memory vs. aMCI patients showing impaired recall but preserved recognition memory. This distinction is usually not taken into account in studies on aMCI and the aim of the present study was to assess whether this distinction is useful. Twenty-eight aMCI patients and 28 matched controls subjects were included. All aMCI patients failed a recall memory task (inclusion criteria). All underwent a visual recognition memory task (DMS48). However, 12 succeeded on this task while 16 failed. Relative gray matter (GM) loss was measured using voxel-based morphometry. When comparing aMCI patients to controls regardless of the profile of memory impairment, GM loss was found in temporal, parietal and frontal areas. However, in aMCI patients with preserved recognition (but impaired recall), GM loss was confined to frontal areas. This contrasted with GM loss in the right medial temporal lobe and bilateral temporo-parietal regions in aMCI patients with impaired recall and recognition memory, a pattern of GM loss usually described in early AD. We conclude that different profiles of memory impairment in aMCI patients are associated with distinct patterns of GM loss.     

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.     

Correlates of recognition memory performance in amnestic mild cognitive impairment

Introduction: Determining whether the etiology of amnestic Mild Cognitive Impairment (aMCI) is Alzheimer’s disease (AD) is challenging. Recognition memory (RM) performance could be helpful in identifying individuals with cognitive patterns indicative of underlying AD. In order to better identify such patterns, we examined RM discriminability in aMCI and its associations with nonmemory cognitive domains impaired in AD.

Methods: Participants were 97 individuals diagnosed with aMCI (M_age = 74.48 years) who underwent comprehensive neuropsychological evaluation. Zero-order correlations and hierarchical linear regression analyses were conducted to determine associations between discriminability on the HVLT-R and specific tasks within the domains of executive function (EF) and language, controlling for age and education. Logistic regression was conducted to determine whether performance on individual tasks was predictive of group membership defined as impaired or unimpaired on RM performance.

Results: While 100% of the aMCI group showed impaired delayed recall on a word list, we found that 69% were impaired on RM discriminability, while 31% were not. Discriminability impairment groups did not differ on demographics or global cognition. For the entire aMCI group, performance in the language domain and, specifically, on a confrontation naming task significantly predicted RM discriminability. Confrontation naming was predictive of RM impairment group membership.

Conclusions: Our results demonstrate individuals with aMCI are heterogeneous and show variability in RM discriminability. RM performance was associated with measures of language, elucidating patterns of cognition potentially marking those more likely to progress to AD. Future studies need to address this finding in a longitudinal sample.     

Alteration of autobiographical memory in amnestic mild cognitive impairment

The concept of amnestic mild cognitive impairment (aMCI) concerns a population of older individuals at high risk of developing probable Alzheimer's disease. Although anterograde memory deficits have been largely documented in patients with aMCI, little is known about the integrity of their autobiographical memory (AuM). This study aimed at evaluating AuM in aMCI individuals and at investigating whether their ability to retrieve AuMs varied as a function of whether the tests used required recognition or effortful retrieval processes. Fourteen aMCI patients and 14 matched controls underwent a standard neuropsychological evaluation and an extensive autobiographical assessment. AuM was explored using verbal material, the Autobiographical Memory Interview, and a visual task of personal photographs. Together, these tests tapped the semantic and episodic components of AuM and different cognitive processes involved in retrieval (recall and recognition). Results indicate that AuM is altered in aMCI patients. This impairment affects both episodic and semantic components of AuM, and is characterized by a general difficulty in recollecting personal episodes covering the entire lifespan, along with a loss of recognition of recently experienced episodes. Furthermore, recollection of personal episodes was correlated with scores on tests requiring retrieval abilities, while recognition of familiar photographs was correlated with scores on tests assessing encoding/storage of new information. Results suggest that the AuM deficit in aMCI patients may result from the combination of two mechanisms, an anterograde memory impairment impeding the storage of newly experienced events, and a global alteration of recollection affecting the recall of AuM covering all periods of life. Alteration of these processes may possibly be related to the progression and distribution of the neuropathological lesions in medial temporal and frontal lobe structures found in Alzheimer's disease.     

Topographical recognition memory sensitive to amnestic mild cognitive impairment but not to depression

OBJECTIVE: Amnestic mild cognitive impairment (aMCI) involves episodic memory. The person who presents aMCI has a high risk of developing Alzheimer's disease (AD). However, prediction of deterioration to dementia in cases of aMCI can be confounded with depression due to lack of specificity on selective memory tests. Finding a test sensitive to aMCI but not to depression would be potentially most useful to subsequent longitudinal studies researching the neuropsychological markers of preclinical AD. We hypothesized that the performance on a topographical memory task would be sensitive to the aMCI condition, while depression would not influence such a performance. PARTICIPANTS AND METHODS: A group of 137 community-dwelling French-speaking subjects between 55 and 70 years old was administered a topographical recognition memory task. Based on aMCI and depression criteria, 45 subjects were selected and divided into four groups: 11 patients with aMCI without depression, nine depressive patients with aMCI, ten depressive patients without cognitive impairment and 15 control subjects. The remaining non-selected participants did not belong to any of the previous interest groups. RESULTS: The 'aMCI' factor had a significant effect on the topographical recognition memory task scores, while the 'depression' factor did not. The aMCI patients performed worse than the non-aMCI. CONCLUSION: Although these results were found with relatively small groups, deficits in topographical recognition memory were observed in aMCI patients and did not seem to be sensitive to depression. Further longitudinal studies are needed to examine whether deficits in topographical recognition memory are a neuropsychological marker of preclinical AD.     

Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) is characterized by decline in anterograde memory as measured by the ability to learn and remember new information. We investigated whether retrograde memory for autobiographical information was affected by aMCI. Eighteen control (age 66-84 years) and 17 aMCI (age 66-84 years) participants described a personal event from each of the five periods across the lifespan. These events were transcribed and scored according to procedures that separate episodic (specific happenings) from semantic (general knowledge) elements of autobiographical memory. Although both groups generated protocols of similar length, the composition of autobiographical recall differentiated the groups. The aMCI group protocols were characterized by reduced episodic and increased semantic information relative to the control group. Both groups showed a similar pattern of recall across time periods, with no evidence that the aMCI group had more difficulty recalling recent, rather than remote, life events. These results indicate that episodic and semantic autobiographical memories are differentially affected by the early brain changes associated with aMCI. Reduced autobiographical episodic memories in aMCI may be the result of medial temporal lobe dysfunction, consistent with multiple trace theory, or alternatively, could be related to dysfunction of a wider related network of neocortical structures. In contrast, the preservation of autobiographical semantic memories in aMCI suggests neural systems, such as lateral temporal cortex, that support these memories, may remain relatively intact.     

老年遗忘型轻度认知损害患者语言工作记忆损害特点

目的 探讨老年遗忘型轻度认知损害(aMCI)患者语言工作记忆损害的特点及机制.方法 采用语言工作记忆检查软件对30例老年aMCI患者进行视觉语言工作记忆及词语流畅性和数字广度测试等神经心理学检查,并选择30名健康老人作对照.结果 aMCI患者的视觉语义工作记忆测试成绩正确率低于对照组,差异具有统计学意义(79.83%±3.22%与87.00%±1.93%,t=-1.03,P=0.002);视觉语音工作记忆测试成绩也低于对照组,但差异无统计学意义(78.92%±8.60%与86.80%±2.14%,t=-2.34,P=0.060);逆序数字广度测试(1.53±0.86与3.63±0.56,t=-1.23,P=0.027)和词语流畅性测试分值均低于对照组(22.96±2.31与31.53±3.72,t=-1.08,P=0.004),差异具有统计学意义.结论 老年aMCI患者的视觉语义性语言工作记忆受损,语音性语言工作记忆相对保留;逆序数字广度和词语流畅性测试成绩亦显著降低.     

Dynamic working memory performance in individuals with single-domain amnestic mild cognitive impairment

Previous studies have observed poorer working memory performance in individuals with amnestic mild cognitive impairment than in healthy older adults. It is unclear, however, whether these difficulties are true only of the multiple-domain clinical subtype in whom poorer executive functioning is common. The current study examined working memory, as measured by the self-ordered pointing task (SOPT) and an n-back task, in healthy older adults and adults with single-domain amnestic mild cognitive impairment (aMCI). Individuals with single-domain aMCI committed more errors and required longer to develop an organizational strategy on the SOPT. The single-domain aMCI group did not differ from healthy older adults on the 1-back or 2-back, but had poorer discrimination on the 3-back task. This is, to our knowledge, the first characterization of dynamic working memory performance in a single-domain aMCI group. These results lend support for the idea that clinical amnestic MCI subtypes may reflect different stages on a continuum of progression to dementia and question whether standardized measures of working memory (span tasks) are sensitive enough to capture subtle changes in performance.     

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.     

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.
Methods:  We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls.
Results:  Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices.
Discussion:  We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.     

MRI evidence of bilateral hippocampal sclerosis in amnestic mild cognitive impairment

We present the case of a man affected by amnestic mild cognitive impairment (aMCI) who showed bilateral hippocampal sclerosis at magnetic resonance imaging (MRI). We argue the concept that aMCI is heterogeneous syndrome and suggested the utility of coronal T2-weighted MRI images in the routine dementia workup.     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

Event-based prospective memory failure in amnestic mild cognitive impairment

Prospective memory (PM) deficits have recently been documented in individuals with amnestic mild cognitive impairment (aMCI). In this paper, we investigated whether these deficits are due to the failure of retrospective memory processes. We also examined the role played by attentional/executive processes in PM functioning.We enrolled 24 individuals with aMCI and 24 healthy controls (NCs). In the PM procedure, we manipulated both the memory load of the retrospective component of the PM task and the complexity of the ongoing task in a 2 × 2 experimental design. Sequences of four words were presented. Participants had to repeat the sequence in the same order (low attentional demand condition) or in the reverse order (high attentional demand condition). When a target word appeared in the sequence, participants had to press a button on the keyboard (PM task). Target words could be one (low memory load condition) or four (high memory load condition) in different blocks.MCI participants obtained lower PM scores than NCs in all four experimental conditions. However, they recalled the target words less accurately than NCs only in one four-word condition. Finally, the executive demand of the ongoing task did not significantly affect the PM performance of aMCI individuals.Our findings confirm that PM is severely impaired in individuals with aMCI. Moreover, a failure of retrospective memory processes does not seem to fully account for the poor PM performance in aMCI individuals. Finally, the finding that in these individuals, a deficit in executive control cannot be claimed as the main responsible for the observed PM impairment could suggest the involvement of automatic-reflexive processes.     

Inefficient response inhibition in individuals with mild cognitive impairment

Individuals diagnosed with mild cognitive impairment (MCI) show primary deficits in memory and are at increased risk for developing Alzheimer's disease (AD). In light of recent evidence that executive cognitive deficits are common in AD and may be detectable in individuals diagnosed with MCI, we extend these findings to the investigation of response inhibition, an essential aspect of executive cognitive control. Twenty MCI patients and 20 healthy controls (HC) completed an arrow version of the flanker task [Eriksen, B. A., & Eriksen, C. W. (1974). Effects of noise letters upon the identification of target letters in a non-search task. Perception & Psychophysics, 16, 143-149] in which participants responded to a target arrow surrounded by distractors (i.e., flankers) that signaled a same (congruent) or a conflicting (incongruent) response. Reaction time (RT) increased in both groups when flankers signaled an incongruent response, but more so among MCI patients. MCI patients taking a cholinesterase inhibitor showed smaller flanker interference effects than those not taking this medication. Analysis of the flanker effect as a function of the entire RT distribution indicated that MCI patients show increasing interference at the slowest segments of the distribution, a finding that implicates deficient inhibition of the incongruent response [Ridderinkhof, K. R. (2002). Activation and suppression in conflict tasks: Empirical clarification through distributional analyses. In W. Prinz & B. Hommel (Eds.), Common mechanisms in perception and action. Attention & performance, Vol. XIX (pp. 494-519). Oxford: Oxford University Press]. These results suggest that deficits in response inhibition are detectable in MCI patients and merit further investigation as to whether these changes aid prediction of which MCI patients convert to AD.     

A clinical memory battery for screening for amnestic mild cognitive impairment in an elderly chinese population

Amnestic mild cognitive impairment (MCI) might be more likely to progress to Alzheimer’s disease than single non-memory MCI and multiple domain MCI. After excluding those who did not conform to the inclusion criteria of amnestic MCI or healthy controls, a neuropsychologic battery that included the Mini-Mental State Examination, Clinical Dementia Rating, Chinese version of the Montreal Cognitive Assessment, Instrumental Activities of Daily Living scale and Auditory Verbal Learning Test was performed on 150 amnestic MCI and 150 normal control patients. The Chinese version of the Montreal Cognitive Assessment was measured for its test-retest reliability, sensitivity and specificity. Blood was collected for apolipoprotein E (APOE) genotyping. Compared with the control group, the amnestic MCI group performed significantly worse on all neuropsychological tests, and non-APOE-??4 carriers in the amnestic MCI group performed better than APOE-??4 carriers in the amnestic MCI group. The set of neuropsychological tests in our study could distinguish amnestic MCI participants from normal elderly participants accurately. APOE did have a role in amnestic MCI patients, but the magnitude and mechanism of its influence are not fully understood.     

Vascular risk factors and white matter hyperintensities in patients with amnestic mild cognitive impairment

BACKGROUND: Subjects affected by aMCI are considered at high risk for AD. Nevertheless, the role of both vascular risk factors and WMH is matter of debate. PATIENTS AND METHODS: We enrolled consecutively 21 aMCI subjects according to Petersen Criteria; the study included routine screening for dementia, neuropsychological evaluation and brain MRI. Six vascular risk factors were assessed and WMH was quantified by means of a semiautomatic lesion-detection program. RESULTS: Conversion to AD, according to NINCDS-ADRDA criteria, was 47.6%. Converters tended to be more affected by the most of vascular risk factors while no difference was noted in WMH. The best predictors of conversion to AD were scores obtained at several neuropsychological examination. CONCLUSION: Our results show that criteria for aMCI identify subjects with a high risk to develop AD. WMH doesn't seem to have a role in progression from aMCI to AD, while some vascular risk factors seem to promote it.     

轻度认知障碍老年人情节记忆功能的磁共振成像研究

目的 运用核磁共振(MRI)技术探讨轻度认知障碍(MCI)老人与健康老人脑结构和功能的异同.方法 对14例MCI老人(MCI组)和15名健康老人(正常对照组)进行神经心理学检查,并应用基于体素的形态测量方法 ,测定两组的灰质体积,并用事件相关功能MRI技术,测定两组在执行情节记忆提取任务时相关脑区的功能变化.结果 (1)神经心理学:MCI组听觉词语记忆测试[(2.1±1.7)分]和画钟试验[(7.8±1.2)分]成绩差于正常对照组[分别为(9.2±1.3)分和(9.2±0.8)分;P＜0.05].(2)结构影像:MCI组的灰质体积小于正常对照组,主要位于情节记忆相关脑区(P＜0.001).(3)功能影像:MCI组与正常对照组任务正确率和反应时间的差别无统计学意义;MCI组激活降低的脑区主要是海马旁回,而增强激活的脑区主要是前额叶前侧、背外侧、右侧颞上回、右侧颞下回、枕叶皮层(P＜0.005).结论 MCI组内侧颞叶记忆系统结构萎缩、功能下降,在任务难度适当的情节记忆提取任务中,MCI组动员额外脑区激活,以代偿颞叶内侧记忆系统的损害.     

Task switching capacities in persons with Alzheimer's disease and mild cognitive impairment

Task switching is an executive capacity that relies on a set of separate components implicating a fronto-parietal network of brain areas. In the present study, different components implicated in task switching were assessed in persons with Alzheimer's disease (AD), persons with mild cognitive impairment (MCI), and their matched healthy controls. The procedure implicated presentation of a two-digit stimulus, and task switching involved either conceptual or spatial switching. Global switching was measured by comparing blocks that involved non-switch trials to blocks that included switch trials, whereas local switching was measured by comparing performance across single trials in the switch blocks. Furthermore, the paradigm measured practice effects. Persons with AD showed larger local and global switch cost than healthy controls suggesting that their deficits encompass both reconfiguration of new action sets and maintenance of potentially relevant tasks within working memory. Importantly, the deficit was large in spatial switching but negligible in the conceptual condition. Persons with MCI only showed global switching impairment, suggesting a deficit restricted to the concurrent maintenance of two relevant task sets, and as in AD, this impairment was limited to spatial switching. Interestingly, persons with MCI, but not AD patients, improved their switching capacities upon practice. These findings indicate that switching deficit is selective in both MCI and AD persons, and is thus supportive of the notion that different mechanisms are involved in task switching. The pattern across condition is coherent with a continuum between those two clinical groups.