Symptoms underlying unawareness of memory impairment in patients with mild Alzheimer's disease

Patients with Alzheimer's disease (AD) are often unaware of their cognitive impairment. This unawareness might have a multifactorial etiology, including impairment of cognitive domains and psychiatric symptoms. We conducted this study to determine the factors underlying unawareness of memory impairment (UMI) in patients with AD. In 103 patients with mild AD, the UMI was quantified as the difference between the patient's self-rating and the rating of the patient's caregiver on a standardized memory questionnaire system, the Everyday Memory Checklist. We then examined the relationships between UMI and memory, attention, language, visuospatial/constructive perception, frontal lobe function, and psychiatric symptoms. UMI was positively associated with memory impairment and delusions when effects of age, sex, and education were partialled out, suggesting that these symptoms are involved in the formation of UMI in the patients. Thus, existing treatments for memory impairment and delusions may be beneficial for increasing the awareness of mild AD patients of their cognitive impairment.     

A critical review of memory stimulation programs in Alzheimer's disease

The authors describe the memory stimulation programs used in the treatment of Alzheimer's disease (AD) and review their efficacy. Visual imagery, errorless learning, dyadic approaches, spaced retrieval techniques, encoding specificity with cognitive support at retrieval, and external memory aids were the memory stimulation programs used alone or in combination in AD. Preliminary evidence suggests that the errorless learning, spaced retrieval, and vanishing cues techniques and the dyadic approach, used alone or in combination, are efficacious in stimulating memory in patients with AD.     

Mental calculation in mild Alzheimer's disease: A pilot study

The purpose of this study was to determine whether dyscalculia is present in the early stages of Alzheimer's disease (AD) and if it is associated with a characteristic neuropsychological pattern. We examined 28 probable AD patients with scores of 18 or greater on the Mini-Mental State Examination (MMS) and with an educational level of 12 or more years. The ability to perform mental calculation was assessed by two tests: the Stamp Test (ST) and the Serial Seven Subtraction Test (SSST). The other cognitive domains were evaluated with an extensive neuropsychological battery. We found significant differences in performances on the calculation tests between patients and controls. The ST was correlated with attention and visuospatial skills, whereas the SSST was correlated with both receptive language and the MMS; both test were similarly correlated with productive language. This study suggests that impairment in mental calculation can be an early sign of AD. The ST seems to represent a more complex task dependent on attentional resources, whereas the SSST would be a purer measure of anarithmetia.     

Elaborated spaced-retrieval and prospective memory in mild Alzheimer's disease

Prospective memory, or the timely remembering of a planned action, is conceptualised as a cognitive process demanding episodic memory and executive attention. Impairments in these skills are characteristic of the cognitive decline in early Alzheimer's disease, providing an expectation of prominent prospective memory difficulties in this population, and yet surprisingly, memory performance in early Alzheimer's disease has rarely been evaluated within a prospective memory framework. In a preliminary study we demonstrated that older adults with early Alzheimer's disease (n=14), as compared to healthy older adults (n=14), were significantly impaired in a simple experimental paradigm of prospective remembering (a text-reading task). In a subsequent intervention study, we investigated the efficacy of spaced-retrieval for improving the prospective remembering performance of older adults with early Alzheimer's disease (n=16) compared to healthy older adults (n=16) under two learning conditions: a spaced-retrieval technique alone or spaced-retrieval combined with elaborated encoding of task. The majority of the Alzheimer's disease group (63%) demonstrated benefit in prospective remembering in the combined condition as compared to spaced-retrieval alone. Participants with Alzheimer's disease who demonstrated better executive attention (Trail Making- set-shifting) and/or better retrospective memory (Hopkins Verbal Learning Test-Revised- recognition) were more successful in the combined learning condition.     

Elaborated spaced-retrieval and prospective memory in mild Alzheimer's disease

Prospective memory, or the timely remembering of a planned action, is conceptualised as a cognitive process demanding episodic memory and executive attention. Impairments in these skills are characteristic of the cognitive decline in early Alzheimer's disease, providing an expectation of prominent prospective memory difficulties in this population, and yet surprisingly, memory performance in early Alzheimer's disease has rarely been evaluated within a prospective memory framework. In a preliminary study we demonstrated that older adults with early Alzheimer's disease (n = 14), as compared to healthy older adults (n = 14), were significantly impaired in a simple experimental paradigm of prospective remembering (a text-reading task). In a subsequent intervention study, we investigated the efficacy of spaced-retrieval for improving the prospective remembering performance of older adults with early Alzheimer's disease (n = 16) compared to healthy older adults (n = 16) under two learning conditions: a spaced-retrieval technique alone or spaced-retrieval combined with elaborated encoding of task. The majority of the Alzheimer's disease group (63%) demonstrated benefit in prospective remembering in the combined condition as compared to spaced-retrieval alone. Participants with Alzheimer's disease who demonstrated better executive attention (Trail Making – set-shifting) and/or better retrospective memory (Hopkins Verbal Learning Test–Revised – recognition) were more successful in the combined learning condition.     

Cognitive stimulation therapy for Alzheimer's disease: the effect of cognitive stimulation therapy on the progression of mild Alzheimer's disease in patients treated with donepezil

BACKGROUND: There is general consensus regarding the benefit of acetylcholinesterase inhibitors (e.g. donepezil) in Alzheimer's disease (AD). However, the combined effect of acetylcholinesterase and cognitive stimulation therapy (CST) is still controversial. OBJECTIVE: This study examines their combined effect on the progression of cognitive decline in AD by comparing the cognitive performance of 17 AD patients treated with CST and donepezil (combined treatment group) and 13 AD patients treated with donepezil alone (control group). METHODS: Patients in the combined treatment group received 5 mg of donepezil per day and about 20 one-hour CST sessions for one year, whereas the control group received only 5 mg of donepezil per day. The first eight sessions were carried out once a week, and subsequent sessions were generally once every two weeks. The patients were evaluated for changes in cognitive ability by administering the Mini-mental State Examination (MMSE) before the start of CST (baseline) and about one year later (follow-up). RESULTS: A repeated-measure analysis of variance revealed a significant group x time interaction. The MMSE score decreased significantly in the control group, but did not change significantly in the combined treatment group. Three patients in the control group declined by four points on the MMSE, compared to none in the combined treatment group. Effect size (ES) in the control group was relatively large and negative, while the ES in the combined treatment group was close to zero. CONCLUSIONS: The results suggest the possibility that donepezil plus CST slowed the rate of cognitive decline more than the administration of donepezil alone.     

Neuropsychological predictors of everyday memory and everyday functioning in patients with mild Alzheimer's disease

The contributions of executive function, naming, visuoperception, and delayed recall to everyday memory abilities and everyday living activities were examined in a sample (n = 24) of mildly impaired Alzheimer's disease (AD) patients. Everyday memory was rated independently by the patient and by a caregiver, and everyday functioning was rated by a caregiver. For patient-rated everyday memory, verbal recall accounted for 23% of the variance, while naming performance alone accounted for 56% of the variance in caregiver-rated everyday memory. Executive function was a unique and significant predictor of caregiver-rated functional daily living skills, accounting for 40% of the variance. Clinician's ratings of patient unawareness of deficit correlated with the discrepancy between caregiver and patient rating of memory. Caregiver reports of memory impairment appear to be influenced by naming abilities, indicating that language dysfunction may be misinterpreted as reflecting memory impairment. Helping caregivers distinguish between these two abilities may result in more accurate reporting of patients' impairments.     

Automatic and controlled uses of memory in Alzheimer's disease

This study used the process-dissociation procedure (Jacoby, 1991) to examine the contribution of automatic and controlled uses of memory to a stem completion task in 16 patients with Alzheimer's disease (AD) and a matched group of healthy elderly subjects (EC). In an inclusion task subjects attempted to use a studied word to complete three-letter word stems, in an exclusion task they were instructed to complete stems with unstudied words. Relative to patients with AD, EC subjects produced more target word completions under inclusion conditions, and less target word completions under exclusion conditions. The probability of the AD group using studied words to complete stems was invariant across inclusion and exclusion conditions. Estimates derived from the process-dissociation calculations, showed that the performance of the AD patients was mediated entirely by automatic uses of memory, whereas for EC subjects controlled and automatic processes codetermined task performance. Both estimates of controlled and to a lesser extent automatic uses of memory were greater for the EC than the AD subjects, indicating that the stem completion impairment in AD may not be entirely attributable to a deficiency in controlled memory processes but also due to reduced automatic processing.     

Efficacy of a medical food in mild Alzheimer's disease: A randomized,controlled trial

ObjectiveTo investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD).MethodsA total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale–revised, and the 13-item modified Alzheimer's Disease Assessment Scale–cognitive subscale at week 12.ResultsAt 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale–cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study–Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated.ConclusionsSupplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials.     

Semantic organization and verbal episodic memory in patients with mild and moderate Alzheimer's disease

The objective of the present research was to investigate the relationship between semantic organization and cue utilization in mildly and moderately demented patients with Alzheimer's disease (AD). In Experiment 1, subjects were presented with two lists of words: a list with semantically unrelated words and a list with words from four semantic categories presented randomly intermixed. Free recall was assessed and following the organizable list, subjects received a cued recall test. Normal controls, as opposed to mildly and moderately demented patients, showed higher performance in the organizable list as compared to the random list. In addition, normal controls and mildly demented patients benefited from semantic cues in the organizable list and performed at a higher level in total recall as compared to free recall. In Experiment 2, subjects were presented with two lists of words: a list with words from four semantic categories presented randomly intermixed and a list with words from four semantic categories presented clustered, together with information about the organization of the list. Free recall and cued recall, with the category names serving as cues, were assessed. Free recall performance of normal controls was higher in the clustered than in the organizable list, whereas no such effect was observed for the AD patients. Normal controls and mildly demented patients performed at a higher level in total as compared to free recall in both lists, whereas this effect was present only in the clustered list for the moderately demented patients. The overall pattern of results indicates that there are conditions under which memory facilitation from semantic organization may be obtained in AD.     

Procedural memory stimulation in Alzheimer's disease: impact of a training programme

The study evaluates the efficacy of a procedural memory stimulation programme in mild and mild-moderate Alzheimer's disease (AD). Twenty basic and instrumental activities of daily living have been selected, and divided into two groups, comparable for difficulty. Ten normal elderly subjects (age 68.0±4.8 years; MMSE score: 28.7±0.9; education: 7.6±3.5 years) were asked to perform the two groups of daily activities and the time required to perform the tasks of each group was recorded and used as a reference. Ten mild and mild-moderate AD patients (age 77.2±5.3 years; MMSE score: 19.8±3.5; education: 7.3±4.7 years) without major behavioural disturbances constituted the experimental group. Patients were evaluated in all 20 daily activities and the time employed was recorded at baseline and after a 3-week training (1 h/d, 5 d/week) period. Five patients were trained during the 3 weeks on half of the 20 daily activities and the other five patients were trained on the remainder. This procedure was adopted in order to detect separately the improvement in "trained" and "not trained" activities, allowing to control better the effects of the intervention. The assessment of the functional impact of the training was directly measured, through the variation of time employed to perform tasks before and after training. After 3 weeks of training a significant improvement was observed for the trained activities, from 3.6 to 1.9 standard deviations below the performance of the normal elderly controls ( P <0.05). AD patients improved also in not-trained activities from 3.5 to 2.7 standard deviations below the controls'performance ( P <0.05). The rehabilitation of activities of daily living through developing procedural memory strategies may be effective in mild and mild-moderate AD patients.     

A two-year follow-up study of remote memory in Alzheimer's disease

The authors assessed long-term changes in autobiographical and public remote memory in a series of 21 patients with Alzheimer's disease (AD) and 10 age-comparable healthy comparison subjects who underwent two evaluations, with an interval ranging from 24 to 36 months. The assessment consisted of the Remote and Autobiographical Memory Scales and the Buschke Selective Reminding Test. The AD group showed a significantly greater decline on both types of remote memory than the comparison group. Alzheimer's disease patients performed significantly better on recognition than on free-recall, suggesting more severe retrieval than encoding/storage deficits. The decline in anterograde verbal memory correlated significantly with the decline in autobiographical memory, suggesting a common final pathway for both deficits.     

Influence of emotional content and context on memory in mild Alzheimer's disease

Healthy subjects remember emotional stimuli better than neutral, as well as stimuli embedded in an emotional context. This better memory of emotional messages is linked to an amygdalo-hippocampal cooperation taking place in a larger fronto-temporal network particularly sensitive to pathological aging. Amygdala is mainly involved in gist memory of emotional messages. Whether emotional content or context enhances memory in mild Alzheimer's disease (AD) patients is still debated. The aim of the present study is to examine the influence of emotional content and emotional context on the memory in mild AD, and whether this influence is linked to amygdala volume. Fifteen patients affected by mild AD and 15 age-matched controls were submitted to series of negative, positive, and neutral pictures. Each series was embedded in an emotional or neutral sound context. At the end of each series, participants had to freely recall pictures, and answer questions about each picture. Amygdala volumes were measured on patient 3D-MRI scans. In the present study, emotional content significantly favored memory of gist but not of details in healthy elderly and in AD patients. Patients' amygdala volume was positively correlated to emotional content memory effect, implying a reduced memory benefit from emotional content when amygdala was atrophied. A positive context enhanced memory of pictures in healthy elderly, but not in AD, corroborating early fronto-temporal dysfunction and early working memory limitation in this disease.     

Hippocampal morphology and autobiographic memory in mild cognitive impairment and Alzheimer's disease

Autobiographical memory (AM) comprises memories of one's own past that are characterized by a sense of subjective time and autonoetic awareness. AM deficits are among the major complaints of patients with Alzheimer's disease (AD) even in early or preclinical stages. However, little is known on the association between cerebral alterations and AM in mild cognitive impairment (MCI) and AD. In the current study, patients with AD or MCI and healthy controls underwent high-resolution magnetic resonance imaging (MRI) and neuropsychological testing including semi-structured assessment of semantic and episodic AM of distinct lifetime periods. In MRI analysis, FSL-FIRST was used to automatically ascertain volume and shape of the hippocampal formation. Episodic, but not semantic AM loss was associated with morphological changes of the hippocampus, primarily involving the left hemisphere. According to shape analyses, these associations referred to regionally specific rather than global atrophy of the hippocampus. Our study demonstrates that loss of episodic AM early in the course of AD is associated with regionally confined hippocampal atrophy, thus supporting the multiple trace theory for the role of the hippocampus in episodic AM. Our findings are not only relevant for the understanding of memory function, but may also contribute to facilitating the early diagnosis of AD.     

Recognition memory in Alzheimer's disease. A demonstration of a remarkable memory capacity in Alzheimer's disease

A compelling feature of human memory is its striking capacity. Under certain circumstances, subjects can remember large amounts of information even with brief exposure at study. This investigation shows that this ability is preserved even in severely impaired Alzheimer's disease patients, and this holds implications for the clinical management of amnesic patients. To this date, demonstrations of preserved learning and memory capacity in Alzheimer's disease and amnesia have been confined to implicit memory tasks. Since the present results were obtained in an explicit memory task, the finding also holds implications for the understanding of amnesia.