A study of remote memory impairment in Alzheimer's disease by using the family line test

We evaluated remote autobiographical memory impairment in 25 patients with probable Alzheimer's disease (AD) and 25 sex-, age- and education-matched healthy subjects by using a newly developed, highly effective assessment tool for remote memory, the Family Line Test (FLT). The FLT yields a total score, scores for 3 lifetime periods and the duration of remote memory impairment. In the patients with AD, the total score was significantly lower and the duration of remote memory impairment was significantly longer than in the healthy controls. A prominent temporal gradient in remote memory impairment was documented in the patients with AD. The total FLT score and duration of remote memory impairment correlated with recent memory and general cognitive dysfunctions.     

Interaction between memory impairment and depressive symptoms can exacerbate anosognosia: a comparison of Alzheimer's disease with mild cognitive impairment

Objective: To investigate the effects of interactions between memory impairment, depressive symptoms, and anosognosia.

Methods: Anosognosia for memory impairment was assessed in 118 patients with Alzheimer's disease (AD), 47 patients with mild cognitive impairment (MCI), and 17 non-diagnosed controls (NC) using a questionnaire and evaluation of the anosognosia score as the discrepancy between ratings of the patient and a relative. Demographic characteristics, such as the relationship of the patient with the relative and the activities of daily living (ADL) were evaluated. Memory impairment was evaluated with the Rivermead Behavioral Memory Test (RBMT), depressive symptoms were evaluated using the Geriatric Depression Scale (GDS) 15 items version.

Results: In the MCI group, a stepwise multiple regression analysis showed an interaction between RBMT and GDS scores, and simple slope analysis indicated that scores for RBMT at low GDS (-1 standard deviation) were positively correlated with self-rated memory impairment. In the AD group, the relationship of the patient with the relative, ADL, and GDS and RBMT scores were associated with the anosognosia score.

Conclusion: Patients with MCI who have no depressive symptoms may be able to more accurately evaluate their memory impairment than those who have depressive symptoms and patients with AD. The evaluation by relatives, depressive symptoms or ADL of patients may distort evaluation of anosognosia for memory impairment in patients with AD or MCI. It seems necessary to include not only depression scale scores but also results of objective memory tests in the patients’ medical information for the correct assessment of anosognosia.     

Validity of the Japanese version of Rivermead Behavioural Memory Test for evaluation of everyday memory function in patients with mild Alzheimer's disease]

OBJECTIVE: To validate the Japanese version of Rivermead Behavioural Memory Test (RBMT) in evaluating everyday memory function in patients with mild Alzheimer's disease (AD). SUBJECTS AND METHODS: Subjects were 100 patients with probable AD of very mild or mild stages of dementia as measured by the Clinical Dementia Rating (CDR). Scores of the Japanese version of RBMT were correlated with scores of the Alzheimer's Disease Assessment Scale-Cognitive part (ADAS-J Cog) and of the Wechsler Memory Scale-Revised (WMS-R). The everyday disability caused by the impairment of memory function was also assessed with the Memory Checklist (CL), and was correlated with the RBMT scores. In addition, the diagnostic value of the RBMT was examined in 46 pairs of AD patients and healthy subjects; the patients were chosen from the present subjects and the healthy subjects from the participants in the previous RBMT standardization study as one-by-one matched for age, sex, and educational level. RESULTS: Both of the total screening score and profile score of RBMT were significantly correlated with all of the weighted sum scores of verbal, visual, general, and delayed memory tests of the WMS-R and the word recall subtest score of the ADAS-J Cog. Both of the RBMT scores were also highly correlated with the CL score and the memory subscale of the CDR. In the analysis of the diagnostic accuracy, both of the RBMT scores correctly classified 98% of AD patients and 96% of normal volunteers by setting the cut-off scores of 6/5 for the total screening score and of 14/13 for the total profile score. CONCLUSIONS: The RBMT is a useful tool in evaluating everyday memory function in patients with mild AD. This test also accurately differentiates AD patients from healthy individuals.     

Language performance in Alzheimer's disease and mild cognitive impairment: a comparative review

Mild cognitive impairment (MCI) manifests as memory impairment in the absence of dementia and progresses to Alzheimer's disease (AD) at a rate of around 15% per annum, versus 1-2% in the general population. It thus constitutes a primary target for investigation of early markers of AD. Language deficits occur early in AD, and performance on verbal tasks is an important diagnostic criterion for both AD and MCI. We review language performance in MCI, compare these findings to those seen in AD, and identify the primary issues in understanding language performance in MCI and selecting tasks with diagnostic and prognostic value.     

Everyday memory impairment in Parkinson's disease]

Memory impairment has been frequently reported in patients with Parkinson's disease. The traditional tests used in previous studies, however, failed to sufficiently reflect memory performance in everyday life. To investigate everyday memory in patients with Parkinson's disease, an objective test of everyday memory, the Rivermead Behavioural Memory Test (RBMT), and an everyday memory questionnaire were administered to 26 parkinsonian patients and 26 age-matched normal controls. The parkinsonian patients scored significantly lower on the RBMT than the controls (p < 0.01). Moreover, the parkinsonian patients performed especially poorly on subtests related to prospective memory (p < 0.05). These subtests are thought to be sensitive to frontal lobe function. On the everyday memory questionnaire, the parkinsonian patients estimated their own everyday memory to be significantly worse than did the controls (p < 0.01). Further, the patients estimated their everyday memory to be especially poor in comparison with the controls on the sub-items related to recency memory (p < 0.05), source memory (p < 0.01), action slip (p < 0.01), and tip-of-the-tongue phenomenon (p < 0.05). In the patient group, the RBMT score correlated significantly with the scores on the Wisconsin Card Sorting Test (p < 0.05) and tests of verbal fluency (p < 0.05). These results indicate that everyday memory is impaired in patients with Parkinson's disease, and that this impairment is partly related to frontal lobe dysfunction.     

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.     

老年轻度认知障碍记忆损害特点的研究

目的探讨老年轻度认知障碍患者的记忆损害特点,比较不同神经心理学测验对诊断和发现轻度认知障碍的敏感性,筛选临床实用的简捷敏感的神经心理学测验工具。方法轻度认知障碍患者20例,轻度阿尔茨海默病患者26例,健康老年人30名。应用词语回忆测验、图片回忆测验、数字广度测验、本顿视觉保持测验C式A法及D式D法进行测试。结果轻度认知障碍组在图片回忆分、视觉保持测验D式D法正确分及持续错误分上的成绩较正常对照组差(P<0．05);轻度认知障碍组视觉保持测验D法成绩明显差于A法(P<0．01)。结论轻度认知障碍患者对具体视觉形象的记忆能力及对无意义图形的视觉记忆能力受损,存在即刻记忆和延迟记忆障碍,且延迟回忆较即刻回忆损害明显,短时记忆更新的可塑性差;图片回忆测试、本顿视觉保持测验的延迟回忆测试或与即刻回忆联合测试有助于轻度认知障碍的早期发现。     

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis

ObjectivePatients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls.MethodsWe evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor.ResultsPatients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT.SignificancePatients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.     

Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease

OBJECTIVES: To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS: This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS: Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS: Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.     

Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease

Structures of the medial temporal lobes are recognized to play a central role in memory processing and to be the primary sites of deterioration in Alzheimer disease (AD). Mild cognitive impairment (MCI) represents potentially an intermediate state between normal aging and AD. Proton magnetic resonance spectroscopy (MRS) was used to examine brain metabolic changes in patients with AD and MCI in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs) and prefrontal cortices (PFCs). Fourteen patients with MCI, 14 patients with mild AD and 14 age- and sex-matched control subjects were studied. Patients with AD and MCI demonstrated significant reductions of NAA/H(2)O and Cho/H(2)O in the left MTL relative to control subjects. Patients with AD showed mI/H(2)O increases relative to patients with MCI and control subjects in all six regions investigated, and a statistically significant mI/H(2)O increase was measured in the right PTC. Patients with AD and MCI demonstrated the same metabolic pattern in the left MTL, suggesting a similar pathological process underlying memory impairment. Increased mI signal appears to be a neurochemical abnormality associated mostly with AD and the dementia process. Some interhemispheric metabolite asymmetries were increased in AD patients.     

Evaluación ecológica en el deterioro cognitivo leve y enfermedad de Alzheimer mediante el Rivermead Behavioural Memory Test

Introduction

The Rivermead Behavioural Memory Test (RBMT) is a short, ecologically-valid memory test battery that can provide data about a subject's memory function in daily life. We used RBMT to examine daily memory function in patients with mild cognitive impairment (MCI), Alzheimer disease (AD), and in healthy controls. We also evaluated differences between the memory profiles of subjects whose MCI remained stable after 1 year and those with conversion to AD.

Patients and methods

Sample of 91 subjects older than 60 years: 30 controls, 27 MCI subjects and 34 AD patients. Subjects were assessed using MMSE and RBMT.

Results

The 40 men and 51 women in the sample had a mean age of 74.29 ± 6.71 and 5.87 ± 2.93 years of education. For the total profile and screening RBMT scores (P<.001) and total MMSE scores (P<.05), control subjects scored significantly higher than those with MCI, who in turn scored higher than AD patients. In all subtests, the control group (P<.001) and MCI group (P<.05) were distinguishable from the AD group. Prospective, retrospective, and orientation subtests found differences between the MCI and control groups (P<.05). MCI subjects who progressed to AD scored lower at baseline on the total RBMT and MMSE, and on name recall, belongings, story − immediate recall, route − delayed recall, orientation (P<.05), face recognition, story − delayed recall, and messages − delayed recall sections (P<.01).

Conclusions

RBMT is an ecologically-valid episodic memory test that can be used to differentiate between controls, MCI subjects, and AD subjects. It can also be used to detect patients with MCI who will experience progression to AD.     

Multiple cognitive deficits in amnestic mild cognitive impairment

OBJECTIVE: To determine if more widespread cognitive deficits are present in a narrowly defined group of patients with the amnestic form of mild cognitive impairment (MCI). METHODS: From a larger sample of patients clinically diagnosed as meeting the criteria of Petersen et al. for amnestic MCI, we selected 22 subjects who had Clinical Dementia Rating scores of zero on all domains besides memory and orientation. These MCI subjects with presumably isolated memory impairments were compared to 35 age-matched normal controls and 33 very mild Alzheimer's disease (AD) patients on a battery of neuropsychological tests. RESULT: In addition to the expected deficits in episodic memory, the amnestic MCI group performed less well than the controls but better than the AD group on design fluency, category fluency, a set shifting task and the Stroop interference condition. Over half the amnestic MCI group (vs. none of the normal controls) scored at least 1 standard deviation below control means on 4 or more of the nonmemory cognitive tasks. CONCLUSIONS: Isolated memory impairment may be fairly uncommon in clinically diagnosed amnestic MCI patients, even when the criteria for amnestic MCI are fairly narrow. Additional cognitive impairments are likely to include fluency and executive functioning. These more diffuse deficits argue for comprehensive cognitive assessments, even when the patient and family are reporting only memory decline, and are consistent with the increase in attention paid to the heterogeneity of MCI.     

Impact of cognitive impairment on mild dementia patients and mild cognitive impairment patients and their informants

BACKGROUND: The aim of this study was to identify key aspects of the impact of cognitive impairment on patients with mild cognitive impairment (MCI) and mild probable Alzheimer disease (AD) and their informants, and identify overlap and differences between the groups. METHODS: Structured focus group discussions were conducted with MCI patients, AD patients, MCI informants, and AD informants. Participants were recruited from memory clinics in the U.K. and the U.S.A. A total of 20 AD and 20 MCI patients and 16 AD and 11 MCI informants participated. Sessions were content reviewed to identify key impacts of cognitive impairment; results were compared across diagnostic groups and for patients and informants. RESULTS: Seven key themes emerged: uncertainty of diagnosis, skill loss, change in social and family roles, embarrassment and shame, emotionality, insight, and burden. Patients were able to discuss the impact of cognitive impairment on their lives and reported frustration with recognized memory problems, diminished self-confidence, fear of embarrassment, concerns about changing family roles due to cognitive impairment, and anxiety. Informants reported more symptoms and more impairment than did patients and indicated increased dependence on others among patients. CONCLUSION: MCI and mild AD exert substantial burden on patients' lives and the lives of those close to them.     

Reduced neuronal efficacy in progressive mild cognitive impairment: a prospective fMRI study on visuospatial processing

Mild cognitive impairment (MCI) often refers to the preclinical stage of dementia, where the majority develop Alzheimer's disease (AD). Given that neurodegenerative burden and compensatory mechanisms might exist before accepted clinical symptoms of AD are noticeable, the current prospective study aimed to investigate the functioning of brain regions in the visuospatial networks responsible for preclinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Eighteen MCI patients were evaluated and clinically followed for approximately 3 years. Five progressed to AD (PMCI) and eight remained stable (SMCI). Thirteen age-, gender- and education-matched controls also participated. An angle discrimination task with varying task demands was used. Brain activation patterns as well as task demand-dependent and -independent signal changes between the groups were investigated by using an extended general linear model including individual performance (reaction time [RT]) of each single trial. Similar behavioral (RT and accuracy) responses were observed between MCI patients and controls. A network of bilateral activations, e.g. dorsal pathway, which increased linearly with increasing task demand, was engaged in all subjects. Compared with SMCI patients and controls, PMCI patients showed a stronger relation between task demand and brain activity in left superior parietal lobules (SPL) as well as a general task demand-independent increased activation in left precuneus. Altered brain function can be detected at a group level in individuals that progress to AD before changes occur at the behavioral level. Increased parietal activation in PMCI could reflect a reduced neuronal efficacy due to accumulating AD pathology and might predict future clinical decline in patients with MCI.     

The nature of lexico-semantic processing deficits in mild cognitive impairment

Lexico-semantic impairments in Alzheimer disease (AD) have been attributed to abnormalities in both intentional and automatic access to semantic memory. However, the order in which these impairments appear during the course of the disease is unclear. We sought to answer this question by documenting lexico-semantic impairments in 61 subjects with mild cognitive impairment (MCI), a pre-AD stage, and by comparing them to those of 39 AD and 60 normal elderly (NE) subjects. All subjects were tested with intentional access tasks (picture naming and semantic probes), automatic access tasks (lexical decision and priming), and executive function tasks (Stroop and Stroop-Picture naming). Results indicated that the MCI group was only impaired on tasks of intentional access relative to the AD group who was impaired on both types of tasks. Because most MCI subjects eventually develop AD, these results suggest that intentional access to semantic memory is impaired before automatic access. Further, impairments on the Stroop-Picture naming task but not on the Stroop task, suggest that lexico-semantic impairments in the MCI group may be related to inhibition deficits during semantic search. Findings are discussed in light of executive dysfunctions within the framework of semantic memory theories.     

The Semantic Object Retrieval Test (SORT) in amnestic mild cognitive impairment.

BACKGROUND: Between 10% and 15% of patients with the amnestic variety of Mild Cognitive Impairment (MCI) convert to Alzheimer disease (AD) per year. OBJECTIVE: Characterize cognitive markers that may herald conversion from MCI to AD and directly assess semantic memory in patients meeting criteria for amnestic MCI. DESIGN: Thirty-five amnestic MCI patients and 121 healthy aging controls enrolled at an Alzheimer Disease Center received a battery of standard neuropsychologic tests, and the Semantic Object Retrieval Test (SORT), a test that we have developed for the assessment of semantic memory and subsequent name production, and that has been shown to be able to differentiate between normals and patients with AD. RESULTS: On the basis of normative data from the SORT, the MCI subjects could be divided into 2 groups: 10 patients (29%) with a significant semantic impairment (SI+) and 25 without a semantic memory deficit (SI-). There was a significant correlation between all SORT variables and performance on the Boston Naming Test. In this MCI population, significantly impaired SORT performance was associated with a relative decrease in performance on tests of frontal lobe functions, although disruption of thalamic-related processes cannot be excluded as an etiology for semantic memory impairment. CONCLUSIONS: The SORT is a specific test of semantic memory, and is a sensitive measure of semantic memory deficits in patients who otherwise meet criteria for amnestic MCI. Using this specific assessment tool, a significant number of MCI patients were found to have semantic memory deficits. As these patients may be early in the course of possible progression toward dementia, the SORT or other tests of semantic memory may provide important diagnostic or prognostic information in patients with MCI.     

Gender-specificities in Alzheimer's disease and mild cognitive impairment

Background Amnestic Mild Cognitive Impairment (MCI) is a condition with an increased risk for developing Alzheimer's disease (AD). Presently, gender differences are neglected in the assessment of MCI and AD. Methods We examined verbal and visuospatial episodic memory in 143 subjects diagnosed as healthy controls (HC; N = 48, Mini-Mental State Examination (MMSE) 29.2 ± 1.0 (mean ± standard deviation)), MCI (N = 43,MMSE 28.5 ± 1.4), and AD (N = 49, MMSE 25.1 ± 2.2). Findings Female HC and MCI subjects performed better on verbal episodic memory tasks than males. In contrast, visuospatial episodic memory was better in male than female AD patients. Conclusions We interpret the results in light of a genderspecific cognitive reserve and conclude that the gender-specificity of neuropsychological performance needs to be accounted for in clinical diagnosis of Alzheimer’s disease.     

Hippocampal impairment in patients with Essential Tremor

IntroductionThere is growing evidence that a proportion of patients with Essential Tremor (ET) may develop a memory impairment over time. However, no studies have evaluated whether hippocampal damage really occur in ET. This study investigated the macro and micro-structural integrity of the hippocampus in ET subjects using a multimodal MRI approach.MethodsNeuropsychological and MRI data were acquired from 110 participants (60 patients with ET and 50 age-, sex-, and education-matched healthy controls [HC]). Whole-brain T1-weighted and Diffusion Tensor Imaging (DTI) were performed to assess macro-and microstructural alterations. MRI parameters (volume; mean diffusivity [MD]; fractional anisotropy [FA]) of bilateral hippocampi were obtained. In order to evaluate the relationship between MRI alterations and neurocognitive impairment, hippocampal parameters were also correlated with cognitive test scores.ResultsCompared to controls, ET patients showed a subclinical memory impairment with significantly lower memory scores, but within the normal ranges. Despite the subclinical damage, however, ET patients showed a significant increase in MD values in the bilateral hippocampi in comparison with HC. A significant correlation was also found between MD and memory scores in ET.ConclusionThis study improves the knowledge on memory impairment in ET, as our results demonstrate for the first time the hippocampal microstructural damage related to subclinical memory impairment in ET patients. Further studies are needed before these findings can be considered predictive of a distinct ET subtype or suggestive of a co-occurent dementia.     

Visual and visuospatial short-term memory in mild cognitive impairment and Alzheimer disease: role of attention

It has been proposed that visual recognition memory and certain attentional mechanisms are impaired early in Alzheimer disease (AD). Little is known about visuospatial recognition memory in AD. The crucial role of the hippocampus on spatial memory and its damage in AD suggest that visuospatial recognition memory may also be impaired early. The aim of the present study was to evaluate which modality, i.e. visual or visuospatial, is more implicated in the early memory impairment in AD. First, to determine onset of memory impairment, we compared the performances of patients with AD to those with amnestic mild cognitive impairment (MCI). Second, to determine the relative contribution of attentional impairment on the performance of MCI and AD patients, we tested the influence of a distractor in the interval between the memory image and recognition tests. Results showed that visuospatial short-term deficits appear earlier than visual short-term ones. In addition to mnemonic deficits, results showed attentional deficiency in both MCI and AD patients. Deficits of performances in visual modality seemed of attentional origin whereas those of visuospatial modality seemed of memory origin. The combination of attentional and mnemonic evaluation is likely to be a promising approach to finding predictive markers that distinguish MCI patients that convert to AD.