Memory In Alzheimer's Disease Research Articles

Algorithmic Spaced Retrieval Enhances Long-Term Memory in Alzheimer Disease: Case-Control Pilot Study.

Spaced retrieval is a learning technique that involves engaging in repeated memory testing after increasingly lengthy intervals of time. Spaced retrieval has been shown to improve long-term memory in Alzheimer disease (AD), but it has historically been difficult to implement in the everyday lives of individuals with AD. This research aims to determine, in people with mild cognitive impairment (MCI) due to AD, the efficacy and feasibility of a mobile app that combines spaced retrieval with a machine learning algorithm to enhance memory retention. Specifically, the app prompts users to answer questions during brief daily sessions, and a machine learning algorithm tracks each user's rate of forgetting to determine the optimal spacing schedule to prevent anticipated forgetting. In this pilot study, 61 participants (young adults: n=21, 34%; healthy older adults: n=20, 33%; people with MCI due to AD: n=20, 33%) used the app for 4 weeks to learn new facts and relearn forgotten name-face associations. Participation during the 4-week period was characterized by using the app once per day to answer 15 questions about the facts and names. After the 4-week learning phase, participants completed 2 recognition memory tests approximately 1 week apart, which tested memory for information they had studied using the app as well as information they had not studied. After using the mobile app for 1 month, every person with MCI due to AD demonstrated improvements in memory for new facts that they had studied via the app compared to baseline (P<.001). All but one person with MCI due to AD (19/20, 95%) showed improvements of more than 10 percentage points, comparable to the improvements shown by young adults and healthy older adults. Memory for name-face associations was similarly improved for all participant groups after using the app but to a lesser degree. Furthermore, for both new facts and name-face associations, we found no memory decay for any participant group after they took a break of approximately 1 week from using the app at the end of the study. Regarding usability, of the 20 people with MCI due to AD, 16 (80%) self-adhered to the app's automated practice schedule, and half of them (n=10, 50%) expressed an interest in continuing to use it. These results demonstrate early evidence that spaced retrieval mobile apps are both feasible for people with early-stage AD to use in their everyday lives and effective for supporting memory retention of recently learned facts and name-face associations.

BDNF serum concentrations in 2053 participants of the Berlin Aging Study II

Serum BDNF concentrations in 2053 participants of the Berlin Aging Study II (BASE-II; 1572 individuals from the older age group [60–85 years], 481 individuals from the younger-age reference group [22–37 years]) were studied. There was no effect of age, sex, body mass index, self-reported depression, or BDNF Val66Met variant on serum BDNF concentrations. Multiple linear regression analysis failed to detect significant relationships of Digit Symbol Substitution Test score and Consortium to Establish a Registry for Alzheimer's Disease memory score to BDNF levels. However, we detected a positive correlation between platelet counts and BDNF levels (r = 0.303, p < 0.001). Our findings do not support an effect of aging, self-reported depression, or the Val66Met variant on serum BDNF concentrations. The role of thrombocytes in the biology of serum BDNF merits further study.

111 - Surface neuromodulation (TMS and tDCS) for therapy of cognitive and psychiatric disorders

The field of neuromodulation has progressed significantly over the past two decades. It is evident that application of electrical (via tDCS, transcranial direct current stimulation) or magnetic (via rTMS, repetitive transcranial magnetic stimulation) brain stimulation over the skull surface can effect change in brain function, which appears sufficiently robust to have a therapeutic effect. Sometimes the neuromodulation is best coupled with other forms of training or rehabilitation for best efficacy. What are the most promising approaches? What conditions appear to benefit? What are the situations/diseases/ disease states where neuromodulation is sufficiently well-proven now (or may be so in the future) that clinicians should start to consider its use in their psychogeriatric practice? We will review studies showing that tDCS can have a therapeutic effect in dementia, stroke, depression, and a range of other psychiatric conditions. Recent work is showing that with tDCS one can achieve improvement in picture naming, executive function, and memory in Alzheimer Disease and Frontotemporal dementia (Howard Chertkow presentation, Baycrest Health Sciences, Toronto). In stroke rehabilitation, rTMS treatment has been shown to aid in motor and language recovery (Alex Thiel, McGill University). There is now sufficient evidence that tDCS and Magnetic Seizure therapy are beneficial in depression, that these can now become part of the therapeutic armamentarium in selected cases (Jeff Daskalakis, University of Toronto). A range of other neuropsychiatric conditions can also be considered for neuromodulation therapy with rTMS (Daniel Blumberger, University of Toronto, CAMH).By attending this symposium, a physician or health care professional will become familiar with the latest research into neuromodulation and its role in current therapy of neurological and psychiatric diseases.

Usefulness of Discriminability and Response Bias Indices for the Evaluation of Recognition Memory in Mild Cognitive Impairment and Alzheimer Disease

Background: Most studies examining episodic memory in Alzheimer disease (AD) have focused on patients' impaired ability to remember information. This approach provides only a partial picture of memory deficits since other factors involved are not considered. Objective: To evaluate the recognition memory performance by using a yes/no procedure to examine the effect of discriminability and response bias measures in amnestic mild cognitive impairment (a-MCI), AD dementia, and normal-aging subjects. Methods: We included 43 controls and 45 a-MCI and 51 mild AD dementia patients. Based on the proportions of correct responses (hits) and false alarms from the Rey Auditory Verbal Learning Test (RAVLT), discriminability (d′) and response bias (C) indices from signal detection theory (SDT) were calculated. Results: Results showed significant group differences for d′ (F (2) = 83.26, p < 0.001), and C (F (2) = 6.05, p = 0.00). The best predictors of group membership were delayed recall and d′ scores. The d′ measure correctly classified subjects with 82.98% sensitivity and 91.11% specificity. Conclusions: a-MCI and AD dementia subjects exhibit less discrimination accuracy and more liberal response bias than controls. Furthermore, combined indices of delayed recall and discriminability from the RAVLT are effective in defining early AD. SDT may help enhance diagnostic specificity.

Emotional Working Memory in Alzheimer’s Disease Patients

Background: Few studies have assessed whether emotional content affects processes supporting working memory in Alzheimer disease (AD) patients. Methods: We assessed 22 AD patients and 40 elderly controls (EC) with a delayed matching and non-matching to sample task (DMST/DNMST), and a spatial-delayed recognition span task (SRST; unique/varied) using emotional stimuli. Results: AD patients showed decreased performance on both tasks compared with EC. With regard to the valence of the stimuli, we did not observe significant performance differences between groups in the DMST/DNMST. However, both groups remembered a larger number of negative than positive or neutral pictures on unique SRST. Conclusion: The results suggest that AD patients show a relative preservation of working memory for emotional information, particularly for negative stimuli.

Val 8-glucagon-like peptide-1 protects against Aβ1–40-induced impairment of hippocampal late-phase long-term potentiation and spatial learning in rats

Amyloid β protein (Aβ) is considered to be partly responsible for the impairment of learning and memory in Alzheimer disease (AD). In addition, it has been found recently that type 2 diabetes mellitus (T2DM) is a risk factor for developing AD. One promising treatment for AD is using analogues for the insulin-release facilitating gut hormone glucagon-like peptide-1 (GLP-1) that has been developed as a T2DM therapy. GLP-1 has been shown to have neuroprotective properties. However, if GLP-1 can protect the late phase-long term potentiation (L-LTP) and related cognitive function against Aβ-induced impairment it is still an open question. To further characterize the neuroprotective function of GLP-1 in the brain, we investigated the effects of i.c.v. injected Val 8-GLP-1(7–36) on the Aβ fragment-induced impairment of in vivo hippocampal L-LTP and spatial learning and memory in rats. The results showed that (1) Aβ1–40 (5 nmol) injection did not affect the baseline field excitatory postsynaptic potentials (fEPSPs), but significantly suppressed multiple high frequency stimulation (HFS)-induced L-LTP in hippocampal CA1 region; (2) Val 8-GLP-1(7–36) (0.05 pmol) administration alone did not affect the baseline synaptic transmission and the maintenance of L-LTP; (3) pretreatment with Val 8-GLP-1(7–36) (0.05 pmol) effectively prevented Aβ1–40-induced deficit of L-LTP; (4) i.c.v. injection of 5 nmol Aβ1–40 resulted in a significant decline learning a spatial Morris water maze (MWM) test; (5) Val 8-GLP-1(7–36) (0.05 pmol) administration alone did not affect spatial learning in this task, while pretreatment with Val 8-GLP-1(7–36) effectively reversed the impairment of spatial learning and memory induced by Aβ1–40. At the same time, the swim speeds and escape latencies of rats among all groups in the visible platform tests did not show any difference. These results suggest that increase of GLP-1 signalling in the brain may be a promising strategy to ameliorate the degenerative processes observed in AD.

Transcranial direct current stimulation improves recognition memory in Alzheimer disease

To evaluate the cognitive effect of transcranial direct current stimulation (tDCS) over the temporoparietal areas in patients with Alzheimer disease (AD). In 10 patients with probable AD, we delivered anodal tDCS (AtDCS), cathodal tDCS (CtDCS), and sham tDCS (StDCS) over the temporoparietal areas in three sessions. In each session recognition memory and visual attention were tested at baseline (prestimulation) and 30 minutes after tDCS ended (poststimulation). After AtDCS, accuracy of the word recognition memory task increased (prestimulation: 15.5 +/- 0.9, poststimulation: 17.9 +/- 0.8, p = 0.0068) whereas after CtDCS it decreased (15.8 +/- 0.6 vs 13.2 +/- 0.9, p = 0.011) and after StDCS it remained unchanged (16.3 +/- 0.7 vs 16.0 +/- 1.0, p = 0.75). tDCS left the visual attention-reaction times unchanged. Transcranial direct current stimulation (tDCS) delivered over the temporoparietal areas can specifically affect a recognition memory performance in patients with Alzheimer disease (AD). Because tDCS is simple, safe and inexpensive, our finding prompts studies using repeated tDCS, in conjunction with other therapeutic interventions for treating patients with AD.

Alzheimer's Memory

Alzheimer's Memory

Profiles of neuropsychological impairment in autopsy-defined Alzheimer's disease and cerebrovascular disease

Differentiating the cognitive effects of cerebrovascular disease, particularly small vessel disease, from those of Alzheimer's disease is a difficult clinical challenge. An influential model of how subcortical cerebrovascular disease causes cognitive dysfunction posits that damage to frontostriatal loops impairs frontal lobe function, leading to predominant impairment of executive function and secondary impairments of associated cognitive functions such as memory. Consistent with this, neuropsychological studies of clinically diagnosed patients have reported that individuals with vascular dementia do better on memory tests and worse on executive function tests compared with patients with Alzheimer's disease. This observation has led to the suggestion that predominant cognitive executive dysfunction might serve as a useful diagnostic marker for vascular dementia. We sought to test this idea in a series of cases with autopsy-defined pathologies. Subjects were 62 autopsied cases from a prospective study of vascular contributions to dementia. Using neuropathological features alone, 23 were diagnosed with Alzheimer's disease (AD), 11 with cerebrovascular disease (CVD), 9 with both (mixed pathology) and 19 with normal elderly brain (NEB). Three psychometrically matched composite scales of different cognitive abilities were used: Verbal Memory, Nonverbal Memory and Executive Function. Analysis of group data showed that for Alzheimer's disease memory scores were lower than Executive Function by nearly a standard deviation on average. In contrast, and contrary to the model, CVD was rather equally impaired on Executive Function, Verbal Memory and Nonverbal Memory. Individual patterns of cognitive impairment were examined by defining three profiles based on reliable differences between neuropsychological scores to characterize cases with predominant memory impairment, predominant executive dysfunction, and 'other' patterns. Analysis of individual impairment profiles showed that predominant memory impairment was present in 71% of Alzheimer's disease while predominant executive dysfunction described only 45% of CVD. A stronger pattern emerged when cognitively normal cases were excluded; among the six cognitively impaired CVD patients four had predominant executive dysfunction and none had predominant memory impairment. This report, comprised of a substantial sample of autopsy confirmed cases, delineates the patterns of neuropsychological impairment associated with small vessel cerebrovascular disease and Alzheimer's disease While the findings show that memory loss usually exceeds executive dysfunction in patients with Alzheimer's disease, the reverse is not the case in CVD. Taken as a whole, the results indicate that the cognitive effects of the small vessel cerebrovascular disease are variable and not especially distinct, thus raising question about the utility of executive impairment as a diagnostic marker for vascular dementia.

Semantic Memory Disorders in Alzheimers Disease: Clues from Semantic Priming Effects

Semantic memory deficits are a common landmark in Alzheimer's disease, but the nature of these impairments remains to be clarified. The tests used to explore this memory system are not specific and involve cognitive processes often disturbed in Alzheimer's disease. A complementary way to investigate semantic memory in neuropsychology is by using the semantic priming paradigm. Here, semantic priming refers specifically to the modification of a stimulus processing behind the presentation of a related stimulus; it is a short-lived phenomenon considered an implicit measure of semantic memory integrity. However, semantic priming studies have yielded contradictory results in Alzheimer's disease, with authors reporting normal priming, less-than-normal priming, or increased priming effects (hyperpriming). The aim of this paper is to review the literature investigating semantic priming in Alzheimer's disease, and to discuss the contradictory results in the context of current models of semantic processing. For a clear comprehension of the semantic priming patterns in this pathology, we will precise the methodology used and the characteristics of the Alzheimer's disease patients examined. Besides, the surprising hyperpriming phenomenon - often observed in Alzheimer's disease at the early stage of dementia--will also be explained in detail. These results from semantic priming represent invaluable clues to widen our knowledge and conceptions about deterioration of the semantic memory in Alzheimer's disease.

P2-210 Regional MR brain volumes in the prediction of cognitive decline in ad

P2-210 Regional MR brain volumes in the prediction of cognitive decline in ad

Action-based memory in Alzheimer's disease: a longitudinal look at tea making

Action-based memory in Alzheimer's disease: a longitudinal look at tea making

Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose.

Increasing plasma glucose levels improves memory in patients with Alzheimer disease (AD). Increasing plasma glucose levels also increases endogenous insulin levels, raising the question of whether memory improvement is due to changes in insulin, independent of hyperglycemia. We address this question by examining memory and counterregulatory hormone response during hyperglycemia when endogenous insulin was suppressed by concomitant infusion of the somatostatin analogue octreotide (Sandostatin). Twenty-three patients with AD and 14 similarly aged healthy adults participated in 4 metabolic conditions on separate days: (1) hyperinsulinemia (538 pmol/L) with fasting glucose (5.6 mmol/L [100 mg/dL]), achieved by insulin and variable dextrose infusion; (2) hyperglycemia (12.5 mmol/L [225 mg/dL]) with fasting insulin (57 pmol/L), achieved by dextrose and somatostatin (octreotide) infusion (150 mg/h); (3) placebo with isotonic sodium chloride solution (saline) infusion (fasting insulin and glucose); and (4) an active control condition in which somatostatin alone was infused (150 mg/h). Declarative memory (story recall) and selective attention (Stroop interference test) were measured during steady metabolic states. Patients with AD showed improved memory during hyperinsulinemia relative to placebo (P = .05) and relative to hyperglycemia (P<.005). Memory did not improve during hyperglycemia when insulin was suppressed. Somatostatin analogue infusion alone also improved memory for patients with AD (P<.05). Hyperinsulinemia increased cortisol levels in subjects with AD, whereas somatostatin alone lowered cortisol concentrations. These results confirm that elevated insulin without hyperglycemia enhances memory in adults with AD, and indicate that insulin is essential for hyperglycemic memory facilitation. These results also suggest a potential therapeutic role for somatostatin in AD.

Semantic memory in Alzheimer's disease: Representativeness, ontologic category, and material.

Alzheimer's disease (AD) patients with semantic memory difficulty and AD patients with relatively preserved semantic memory named pictures and judged the category membership of words and pictures of natural kinds and manufactured artifacts that varied in their representativeness. Only semantically impaired patients were insensitive to representativeness in their category judgments. AD subgroup judgments did not differ for natural kinds compared to manufactured artifacts nor for words compared to pictures. AD subgroup differences could not be explained by dementia severity, memory, reading, and visuoperception. The similarity process for relating coordinate members of a taxonomic category contributes to the normal appreciation of word and picture meaning, and this process is compromised in AD patients with semantic difficulty.

Comparison of verbal memory in Alzheimer's disease, vascular dementia, and healthy elderly

Comparison of verbal memory in Alzheimer's disease, vascular dementia, and healthy elderly

Word-Association Responses and Severity of Dementia in Alzheimer Disease

To test the impairment of semantic memory in Alzheimer Disease, two groups of patients (one French and one American) were given a free-word-association task. Analysis showed a strong correlation between the scores of the Mini-Mental State Examination and an index of commonality of responses in both groups. As the severity of dementia increased, Alzheimer patients were less likely to give common responses. Our results are consistent with those of previous studies showing a relationship between dementia severity and impairment in semantic memory in Alzheimer Disease.

Semantic memory in Alzheimer's disease.

Semantic memory in Alzheimer's disease.

Sparing of semantic memory in Alzheimer's disease.

Sparing of semantic memory in Alzheimer's disease.