Early Dementia Of Alzheimer Type Research Articles

Impact of Current Alcohol Consumption on Cognitive Function in Patients with Self-Perceived Memory Decline: A Comparative Study of Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer-Type Dementia Groups

Background: Alcohol consumption has been considered as a modifiable risk factor for dementia development and alcohol-related brain damage may further impair cognitive abilities in dementia patients. This study aimed to find out the differences in cognitive function according to current alcohol drinking in patients with self-perceived memory decline, including subjective cognitive decline (SCD), mild cognitive impairment (MCI) and early Alzheimer-type dementia (ATD).Methods: From May 2018 to December 2019, retrospective chart review was performed in patients who visited CHA Bundang Medical Center for cognitive decline. A two-way analysis of variance with interaction test were used to analyze the impact of alcohol consumption on cognitive function between groups.Results: A total of 147 patients was classified into three groups of SCD (n=30), MCI (n=53), and ATD (n=64), and each group was divided into two subgroups of alcohol users and alcohol non-users, according to the current status of alcohol consumption. Between SCD, MCI and ATD groups, scores of clock drawing test and Go/No-go test were significantly lower in current alcohol users of ATD groups compared to the SCD and MCI groups (p<0.05).Conclusions: These results suggest that current alcohol consumption has detrimental effects especially on the frontal/executive function in early ATD patients. Considering the association between frontal/executive function and ADL, our finding suggests that cessation of alcohol intake may be a therapeutic strategy to prevent ADL deterioration in patients with ATD.

Electric stimulation of the medial forebrain bundle influences sensorimotor gaiting in humans

BackgroundPrepulse inhibition (PPI) of the acoustic startle response, a measurement of sensorimotor gaiting, is modulated by monoaminergic, presumably dopaminergic neurotransmission. Disturbances of the dopaminergic system can cause deficient PPI as found in neuropsychiatric diseases. A target specific influence of deep brain stimulation (DBS) on PPI has been shown in animal models of neuropsychiatric disorders. In the present study, three patients with early dementia of Alzheimer type underwent DBS of the median forebrain bundle (MFB) in a compassionate use program to maintain cognitive abilities. This provided us the unique possibility to investigate the effects of different stimulation conditions of DBS of the MFB on PPI in humans.ResultsSeparate analysis of each patient consistently showed a frequency dependent pattern with a DBS-induced increase of PPI at 60 Hz and unchanged PPI at 20 or 130 Hz, as compared to sham stimulation.ConclusionsOur data demonstrate that electrical stimulation of the MFB modulates PPI in a frequency-dependent manner. PPI measurement could serve as a potential marker for optimization of DBS settings independent of the patient or the examiner.

Autobiographical Memory Performance in Alzheimer's Disease Depends on Retrieval Frequency.

Alzheimer's disease (AD) is characterized by memory disturbances primarily caused by pathogenic mechanisms affecting medial temporal lobe structures. As proposed by current theories of memory formation, this decrease is mediated by the age of the acquired knowledge. However, they cannot fully explain specific patterns of retrograde amnesia in AD. In the current study we examined an alternative approach and investigated whether the extent and severity of retrograde amnesia in AD is mediated by the frequency of memory retrieval or whether it depends on the mere age of knowledge. We compared recall of autobiographical incidents from three life periods in patients with amnestic mild cognitive impairment (aMCI), patients with early dementia of Alzheimer type (eDAT), and healthy control (HC) individuals using the Autobiographical Memory Interview. Retrieval frequency was operationalized by a paired comparison analysis. In contrast to HC individuals, recall of autobiographical incidents was impaired in patients with aMCI and eDAT following Ribot's gradient, with a reduced memory loss for remote compared to more recent life events. However, there was a strong effect of retrieval frequency on memory performance with frequently retrieved incidents memorized in more detail than less frequently retrieved episodes. Remote memories were recalled more often than recent ones. These findings suggest that more frequently retrieved autobiographical memories generally become more independent of the hippocampal complex and might thus be better protected against early hippocampal damage related to AD. Hence, the extent of retrograde amnesia in AD appears mainly mediated by the frequency of memory retrieval, which could plausibly explain why cognitive activity can effectively delay the onset of memory decline in AD.

Long-term effect of a cognitive intervention on learning and participation in a significant leisure activity in early dementia of Alzheimer type: a case study

Decreased ability to accomplish significant leisure activities often occurs in early stages of dementia of Alzheimer type (DAT). As a long term effect, it may eventually affect the quality of life of the patient as well as that of the caregiver's. In a previous study, a woman with early DAT (77 years old, MMSE: 24/30) improved her participation in 2 leisure activities (listening to music and praying in a group) following the learning of a few tasks (e.g. using a radio cassette, remembering the significance of an pre-programmed ring) as a result of a cognitive intervention. The present study presents the long term effect of this intervention on the retention of the learned tasks and on spontaneous participation in both leisure activities of her daily living. Measures of tasks' learning and spontaneous participation in activities have been obtained through direct observation (ex: ability to use the tasks learned without assistance) and telephone conversations with the caregiver. The measures were taken 9 to 15 months post-intervention. Nine months after the end of the intervention, the participant could no longer use the radio cassette, but was able to remember the significance of the pre-programmed ring. Similarly, she stopped listening to music, but still attended her prayer group. The intervention appears to maintain participation in a leisure activity for several months in a patient with early DAT, in spite of expected functional decline. This functional impact can be achieved through retention of specific learned tasks as well as by strong external cues (daily pre-programmed ring), and can increase the quality of life for patients with DAT.

Face–name association learning in early Alzheimer's disease: A comparison of learning methods and their underlying mechanisms

This study compared the efficacy of five learning methods in the acquisition of face–name associations in early dementia of Alzheimer type (AD). The contribution of error production and implicit memory to the efficacy of each method was also examined. Fifteen participants with early AD and 15 matched controls were exposed to five learning methods: spaced retrieval, vanishing cues, errorless, and two trial-and-error methods, one with explicit and one with implicit memory task instructions. Under each method, participants had to learn a list of five face–name associations, followed by free recall, cued recall and recognition. Delayed recall was also assessed. For AD, results showed that all methods were efficient but there were no significant differences between them. The number of errors produced during the learning phases varied between the five methods but did not influence learning. There were no significant differences between implicit and explicit memory task instructions on test performances. For the control group, there were no differences between the five methods. Finally, no significant correlations were found between the performance of the AD participants in free recall and their cognitive profile, but generally, the best performers had better remaining episodic memory. Also, case study analyses showed that spaced retrieval was the method for which the greatest number of participants (four) obtained results as good as the controls. This study suggests that the five methods are effective for new learning of face–name associations in AD. It appears that early AD patients can learn, even in the context of error production and explicit memory conditions.

Parallel transport in diffeomorphisms distinguishes the time-dependent pattern of hippocampal surface deformation due to healthy aging and the dementia of the Alzheimer's type

Hippocampal surface structure was assessed at twice 2 years apart in 26 nondemented subjects (CDR 0), in 18 subjects with early dementia of Alzheimer type (DAT, CDR 0.5), and in 9 subjects who converted from the nondemented (CDR 0) to the demented (CDR 0.5) state using magnetic resonance (MR) imaging. We used parallel transport in diffeomorphisms under the large deformation diffeomorphic metric mapping framework to translate within-subject deformation of the hippocampal surface as represented in the MR images between the two time points in a global template coordinate system. We then performed hypothesis testing on the longitudinal variation of hippocampal shape in the global template. Both subjects with early DAT and converters showed greater rates of hippocampal deformation across time than nondemented controls within every subfield of the hippocampus. In a random field analysis, inward surface deformation across time occurred in a non-uniform manner across the hippocampal surface in subjects with early DAT relative to the nondemented controls. Also, compared to the controls, the lateral aspect of the left hippocampal tail showed inward surface deformation in the converters. Using surface deformation patterns as features in a linear discriminant analysis, we were able to respectively distinguish converters and patients with early DAT from healthy nondemented controls at classification rates of 0.77 and 0.87, which were obtained in the same training set using the leave-one-out cross validation approach.

Selective attention in early Dementia of Alzheimer Type

This study explored possible deficits in selective attention brought about by Dementia of Alzheimer Type (DAT). In three experiments, we tested patients with early DAT, healthy elderly, and young adults under low memory demands to assess perceptual filtering, conflict resolution, and set switching abilities. We found no evidence of impaired perceptual filtering nor evidence of impaired conflict resolution in early DAT. In contrast, early DAT patients did exhibit a global cost in set switching consistent with an inability to maintain the goals of the task (mental set). We discuss these findings in relation to the DAT literature on executive attention, dual-tasking, and working memory.

Relationship between Hippocampal Atrophy and Cognitive Dysfunction in Early Alzheimer‐type Dementia

Abstract Background: We assessed the relationship between early cognitive dysfunction and morphologic changes in the brain, especially hippocampal atrophy, on MR images in Alzheimer‐type dementia (AID) patients to establish a technique for making an early clinical diagnosis of AID. Methods: The subjects of this study were 82 individuals who visited Kawase Neurology Clinic. They consisted of 41 ATD patients and 41 elderly individuals without dementia who visited the clinic for a neurological checkup or because of vertigo or numbness as age‐matched controls. As an index for hippocampal atrophy, the hippocampal‐intracranial ratio (HIR) was calculated. Discriminant analysis was performed using HIR results and the correct answer rate for recall and calculation items in Mini‐Mental State Examination (MMSE). Results: The mean ratio was significantly lower in the ATD patients than in the controls. This supports our previous results. The results of discriminant analysis with Mahalanobis generalized distance in the 41 controls and 22 ATD patients who scored 15 or higher. The sensitivity and specificity of HIR combined with the correct answer rate for recall and calculation items in MMSE were 95.5% and 95.1%, respectively, with an overall accuracy of 95.2%. Conclusion: HIR combined with the correct answer rate for recall and calculation items in MMSE allows for an early diagnosis of ATD.

Long-term maintenance of treatment gains following a cognitive rehabilitation intervention in early dementia of Alzheimer type: A single case study

It has been suggested that “memory retraining” has no lasting effect beyond the end of the treatment session (Rabins, 1996). Although this is contradicted by cognitive rehabilitation studies showing that gains can be demonstrated and maintained, few researchers have presented long-term follow-up data. Recent studies (Clare, Wilson, Breen, & Hodges, 1999; Clare et al., 2000) have provided post-intervention follow-up data for one participant that was collected over a 9 month period, during which performance on trained face-name associations remained at ceiling levels. This paper reports a further, naturalistic follow-up of this participant over an additional period of two years, during which his recall of 10 trained face-name associations was evaluated and compared to performance on three untrained, previously-known items retained as part of the full set of stimulus materials throughout the whole study. Recall remained relatively stable over year 1 and showed a modest decline for both trained and previouslyknown items during year 2. Differences between year 1 and year 2 were significant only for untrained items. At the end of year 2, performance on trained items remained well above initial baseline levels. These results are discussed in the context of information derived from neuropsychological assessment, scans and self-report measures. It is argued, on the basis of the results presented here, that long-term maintenance of gains resulting from targeted cognitive rehabilitation interventions is possible, and that in view of this it will be important to evaluate the broader impact of cognitive rehabilitation interventions on quality of life and on the progression of dementia.

Intervening with Everyday Memory Problems in Dementia of Alzheimer Type: An Errorless Learning Approach

Dementia of Alzheimer Type (DAT) is increasingly detected at an earlier stage of the disorder, when interventions to assist with everyday memory difficulties might be most valuable. Some learning is possible in DAT and a number of factors have been identified which may facilitate performance, although applications to everyday memory problems have been limited. The concept of errorless learning has not previously been directly examined in relation to DAT, but might provide a useful additional strategy. In the present study, 6 participants with early stage DAT (MMSE scores 21 – 26) received individually tailored interventions, based on errorless learning principles and targeted at a specific everyday memory problem. Five of the participants showed significant improvement on the target measures, and maintained this improvement up to 6 months later. The results suggest that it is feasible to intervene with everyday memory problems in the early stages

2-12-01 Sparing of reaction time on a visual vigilance task in patients with early dementia of Alzheimer type

2-12-01 Sparing of reaction time on a visual vigilance task in patients with early dementia of Alzheimer type

Generation Effect in Short-Term Verbal and Visuospatial Memory: Comparisons Between Dementia of Alzheimer Type and Dementia of Frontal Lobe Type

Memory deficit is the predominant presenting symptom in dementia. To compare shortterm memory (STM) deficit in early dementia of Alzheimer type (DAT) vs frontal lobe type (DFT), and determine the residual memory capacity for stimulation, the generation effect (the memory advantage of items generated rather than read) was tested on verbal and visuospatial STM in patients with DAT (n =10), DFT (n = 9) and in age-matched normal controls (n = 12). The generation effect enhanced performance in all groups. However, the profile of STM deficit differed in the two dementias: verbal and visuospatial memory were both decreased in DAT vs verbal memory only in DFT. These results provide a further criterion for differentiating between DAT and DFT, and show that memory performance can be enhanced in early dementia using techniques such as the generation effect.

Analysis of the episodic memory deficit in early Alzheimer's disease: Evidence from the doors and people test

Anterograde episodic memory was assessed in a cohort of 33 patients with early dementia of Alzheimer type (DAT) and 30 matched controls using immediate and delayed prose recall, the CERAD word learning test and the recently developed doors and people test of visual and verbal recall and recognition. DAT patients showed markedly impaired learning on all three measures, with little evidence of cumulation of information across trials. Patients showed more forgetting than controls on prose recall and the CERAD word list, but more detailed analysis suggested that this differential loss was attributable to the contribution of primary memory to immediate but not delayed recall. No differences in forgetting rate were observed on the doors and people test. Scaled scores were used to derive a recall-recognition index, together with a measure of material-specific memory based on the ratio of verbal to visual memory deficits. There was no evidence for differential sensitivity of recall over recognition, implying that the episodic memory deficit is one of learning, rather than of the retrieval of learned material. Although individuals varied in the relative degree of impairment of verbal and visual memory, there was no general tendency for material-specificity. It was concluded that the episodic memory deficit in DAT is general in nature and primarily reflects impaired learning rather than accelerated forgetting or disrupted retrieval.

Autobiographical memory and executive function in early dementia of Alzheimer type

We studied executive function and autobiographical memory in a cohort of 33 DAT patients [divided into minimal (MMSE 24–30) and mild (MMSE 17–23) groups] and in 30 normal controls. Autobiographical memory, as assessed by autobiographical fluency and the Autobiographical Memory Interview (AMI), was impaired in DAT patients, even those with minimal disease. There was evidence of a gentle temporal gradient on the incident but not the personal semantic component of the AMI, suggesting that the two components are dissociable. Executive function was assessed by two separate dual performance tasks and letter fluency. Although there was a trend for minimal DAT patients to be impaired on executive tasks, this only reached significance for the mild group. Regression analysis suggested that the divided attention component of working memory was involved in the retrieval of personal semantic autobiographical memory, but verbal fluency was more important in the retrieval of autobiographical incidents. There was thus a dissociation in the type of executive function implicated in different subcomponents of autobiographical memory, arguing for subcomponents within executive function and autobiographical memory. The autobiographical memory deficit in DAT reflects, we argue, both impairment in retrieval processes, linked to executive function, and a loss of memory stores.

Is semantic memory consistently impaired early in the course of Alzheimer's disease? Neuroanatomical and diagnostic implications

To establish whether semantic memory is consistently impaired in patients with very mild dementia of Alzheimer's type (DAT), we assessed episodic and semantic memory in 52 patients with DAT who were divided into three sub-groups according to dementia severity on the Mini-Mental State Examination (minimal > 23, mild 17–23 and moderate < 17) and 24 matched controls. The minimal group showed impairment on the following semantic memory measures: category fluency, naming of line drawings, naming to verbal description, answering semantic feature questions and a non-verbal picture-picture matching task (the Pyramids and Palm Trees Test). The mild and moderate groups showed additional deficits on picture sorting and word-picture matching tests. Within the minimal and mild groups there was, however, considerable heterogeneity. While some patients showed a consistent impairment across all of the semantic memory tests, others were impaired only on a subset of these tests and a few even performed flawlessly. In contrast, all patients showed a profound deficit in episodic memory: delayed recall of new verbal and non-verbal material appears to be a particularly sensitive marker of early DAT. These data are in keeping with recent neuropathological studies demonstrating that the transentorhinal region is consistently involved at a very early stage. Lesions in this site cause a functional disconnection of the hippocampus, and hence a profound episodic memory disorder. The fact that many, but not all, patients with early disease also show impairment of semantic memory suggests that damage to the transentorhinal region is not sufficient to produce significant disruption of semantic memory. Such disruption reliably occurs, we hypothesize, only when the pathology extends to the temporal neocortex proper.

Line orientation judgment in normal elderly and subjects with dementia of Alzheimer's type

Ninety-five normal controls divided into three subgroups (55-64 yrs, 65-74 yrs, and 75-84 yrs) and 11 subjects with early dementia of Alzheimer's type (DAT) were given a line orientation judgment task (Benton, Varney, & Hamsher, 1978). No difference appeared between the three control subgroups in global score but the difference between controls and DAT subjects was significant. However, some DAT subjects had a global score overlapping the scores of controls. Error types were also analyzed. Results of this analysis showed that some errors appeared in all subjects, normal and DAT, while others were specific to DAT subjects. It was speculated that these error types were a manifestation of a deeper visuospatial deficit, revealing a major problem of the DAT in spatial organization. Thus, this study suggests that an analysis of the error types observed in the line orientation judgment task may be helpful in differentiating normal elderly from early DAT.

A family-genetic study of dementia of Alzheimer type.

A family study of 22 rigorously diagnosed subjects with dementia of Alzheimer type (DAT) and 24 nondemented controls revealed a morbid risk of DAT to first-degree relatives of probands of 41% by age 83 years compared with a risk of 23% by age 85 years in control relatives. Senescent forgetfulness, defined as consistent but not incapacitating memory deficit, may have represented early DAT in some instances. When such cases were included as secondary cases, the morbid risk to first-degree relatives of probands was 67% by age 86 years while risk to comparable control relatives remained 23%. No cases of Down's syndrome were observed. A significant excess of hematologic malignant neoplasms was found among first-degree relatives of probands, supporting an association with DAT. Overall, the findings add further evidence of the action of familial-genetic factors in the etiology of DAT. The magnitude of the effect is consistent with an autosomal dominant mode of inheritance, with penetrance nearly complete by age 85 years. The probands were not selected on the basis of factors posited by some to indicate a familial form of DAT, suggesting that such a genetic mechanism may be involved in the occurrence of DAT in general.

Word fluency in patients with early dementia of Alzheimer type.

The relative fluency with which 15 patients with Alzheimer-type dementia (DAT) retrieved words with specified first letters and belonging to semantically defined categories was assessed. Patients with DAT were always less fluent than controls but, like the 12 normal elderly subjects, they were more efficient in accessing words belonging to semantic categories. Their deficit in retrieving words with specified first letters was greater than that predicted on the basis of verbal intellectual ability. No differences in word fluency were detected in presenile and senile patients. These data support the conclusion that word fluency may prove useful in the detection of early dementia.

Primary and working memory functioning in Alzheimer-type dementia.

This paper reviews recent neuropsychological studies of primary-memory functioning in early Alzheimer-type dementia (AD) with specific reference to recent research on working memory. The deficits in primary memory follow a fairly distinct pattern with a comparatively unimpaired recency effect in free recall, a moderate impairment in memory span, and a more substantial impairment in short-term retention following distraction. The nature of these deficits is considered in relation to the Working Memory Model (Baddeley & Hitch, 1974). It is suggested that the Articulatory Loop System is functioning normally but that there is an impairment in the control processes of working memory.

The effect of concurrent articulation on memory span in Alzheimer-type dementia.

This study explored the effects of concurrent articulation on memory-span performance, comparing patients with early Alzheimer-type dementia (AD) and matched controls. Reduction in memory span due to concurrent articulation was the same in AD patients as controls, supporting the notion that the contribution of articulatory rehearsal to memory-span performance is undiminished in early AD.