Memory In Alzheimer's Disease Patients Research Articles

Involuntary Autobiographical Memory in Alzheimer's Disease: A Double-Edged Way of Remembering the Past?

Alzheimer's disease (AD) is characterized by severe memory alterations, affecting especially memories of personal past events. Until now, autobiographical memory impairments have been characterized using formal memory assessments, requiring patients to strategically and deliberately recall past events. However, contrary to this highly cognitively demanding mode of memory recall, autobiographical memories frequently come to mind unexpectedly based on automatic associative processes. The involuntary recall of personal memories is effortless and possibly represents a preserved way for AD patients to remember past events. This study aimed to investigate involuntary autobiographical memory in AD patients and compare the characteristics of these memories with those of healthy controls. Involuntary autobiographical memory was measured in 24 AD patients and 24 matched control participants using self-report measures. Participants were asked to report the frequency with which involuntary autobiographical memories were experienced in their daily life and to describe and self-assess one example of an involuntary memory. We showed that AD patients and control participants did not differ in terms of the frequency or subjective characteristics of their involuntary autobiographical memories in daily life, except for feelings of intrusiveness. Compared to control participants, AD patients reported their involuntary autobiographical memories as being more intrusive. In addition, more negative and vague involuntary autobiographical memories were associated with greater depressive symptoms. These findings open up a new avenue for research to better understand the extent to which involuntary autobiographical memory might be preserved in AD patients and why these memories may in turn become intrusive to patients.

Clinical Manifestations.

Associative binding is key to normal memory function and is selectively impaired in Alzheimer's disease (AD).1 Electrophysiological abnormalities are frequently reported in AD including during tasks requiring associative binding.2 We use a precision spatial working memory test to investigate the binding of distinct visual features (object and location) in working memory in AD patients and test the hypothesis that misbinding is related to electrophysiological abnormalities. 36 AD patients and 29 healthy age-matched controls (HC) were tested with a precision working memory paradigm that required the association of object and location information (Fig 1A). Participants were excluded if they were unable to perform the identification element of the task significantly above chance level (p>0.05). High-density eyes-closed resting-state EEG was used to assess changes in electrophysiological power across frequency bands. 25 AD and all HC performed above chance level (Fig 1C). AD patients showed abnormalities in working memory function and made significantly more misbinding errors (p<0.001) than HC (Fig1E) indicating that working memory recall was abnormally biased by the spatial locations of distractor items (Fig 1F). AD patients demonstrated significant reductions in global alpha and increases in global theta (Fig 2A). Channel-wise analysis revealed significant clusters of decreased power in AD across occipital-parietal channels in alpha and beta bands (p<0.05; Fig 2C). Misbinding errors significantly correlated with alpha power in AD but not HC (p<0.05; Fig 2D). These results offer further support for a deficit in working memory binding being a sensitive cognitive biomarker of AD. Pathologically reduced alpha power may offer mechanistic insight into the profound working memory binding impairments seen in AD.

Memory Enhancing and Neurogenesis Activity of Honey Bee Venom in the Symptoms of Amnesia: Using Rats with Amnesia-like Alzheimer's Disease as a Model.

Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD. The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively. During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner. This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.

Differential Outcomes Training Ameliorates Visual Memory Impairments in Patients With Alzheimer's Disease: A Pilot Study.

It is well known that Alzheimer’s disease (AD), the most common form of dementia, is associated with deficits in cognitive processes including visual memory impairments. One technique that might be used to ameliorate these impairments is the differential outcomes procedure (DOP) that involves associating each to-be-remembered stimulus with a specific outcome.Objective: Previous research has demonstrated that the DOP can be used to reduce or eliminate the learning and memory deficits associated with animal models of amnesia and dementia. Furthermore, this procedure has been shown to improve delayed facial recognition in healthy older adults as well as in patients diagnosed with AD. The main aim of the present study is twofold: to extend these findings to other types of visual stimulus and to investigate the effect of the DOP in memory retention in AD patients.Method: Ten patients diagnosed with AD and 10 healthy controls participated in this study. The experiment included two phases. In the first one, they had to perform a delayed matching-to-sample task. In the second phase, participants performed a recognition memory task, designed to assess long-term retention, 1 h and 1 week after the training.Results: Participants showed a better memory-based performance as well as a higher long-term retention of the information when trained under the differential outcomes condition, relative to the non-differential outcomes condition.Conclusions: The DOP seems to be an effective, easy-to-implement, technique to enhance visual memory in AD patients.

MiR-302/367-induced neurons reduce behavioral impairment in an experimental model of Alzheimer's disease

In vivo reprogramming of reactive glial cells to neurons has opened a new horizon in regenerative medicine. Our previous study showed that astrocytes could be converted to neurons by the microRNA-302/367 (miR-302/367) cluster in adult brains. In this study, we investigated the possible contribution of miR-302/367-induced neurons in behavioral improvement and neural repair in an Alzheimer's disease (AD) animal model. The AD model was induced by an intracerebroventricular (i.c.v) injection of streptozotocin (STZ). GFP-only or miR-302/367+GFP expressing lentiviral particles were injected into the dentate gyrus of the hippocampus along with intraperitoneal (i.p) valproate (VPA) injection, 3weeks after the STZ administration. We assessed short-term and spatial memories by the Y-maze and Morris water maze (MWM) tasks, respectively. Electrophysiological activities of induced neuron-like cells were investigated using a whole-cell patch clamp technique, 6months after injection of miR-302/367. Behavioral analysis showed that the STZ injection significantly impaired short-term memory and increased escape latency parameter in the MWM task. Compared to STZ and STZ+VPA groups, miR-302/367 combined with VPA significantly improved the spontaneous alternation and spatial memory. Immunostaining against NeuN, as a mature neuronal marker, and its quantification indicated that co-labeled GFP and NeuN significantly increased in the miR-302/367+VPA group. Induced neurons were detected 6months after the miR-302/367 injection. The patch-clamp recording suggested that induced neurons could fire repetitive action potential like endogenous neurons. In conclusion, our results indicated that in vivo reprogramming of reactive astrocytes to neurons by the miR-302/367 cluster might be considered as a novel strategy to restore learning and memory in AD patients.

Physical activity and beta-amyloid pathology in Alzheimer's disease: A sound mind in a sound body.

Alzheimer's disease (AD) is the most common type of dementia worldwide. Since curative treatment has not been established for AD yet and due to heavy financial and psychological costs of patients' care, special attention has been paid to preventive interventions such as physical activity. Evidence shows that physical activity has protective effects on cognitive function and memory in AD patients. Several pathologic factors are involved in AD-associated cognitive impairment some of which are preventable by physical activity. Also, various experimental and clinical studies are in progress to prove exercise role in the beta-amyloid (Aβ) pathology as a most prevailing hypothesis explaining AD pathogenesis. This study aims to review the role of physical activity in Aβ-related pathophysiology in AD.

Intranasal Insulin Administration Ameliorates Streptozotocin (ICV)-Induced Insulin Receptor Dysfunction, Neuroinflammation, Amyloidogenesis, and Memory Impairment in Rats.

Alzheimer's disease (AD) is associated with reduced insulin level and impairment of insulin receptor (IR) signaling in the brain, which correlates to amyloid pathology, neuroinflammation, and synaptic neurotoxicity. Clinical studies show that intranasal insulin improves memory in AD patients without peripheral hypoglycemia. However, neuroprotective molecular mechanism of the beneficial effect of intranasal insulin in AD pathology is unexplored. Therefore, we investigated the role of intranasal insulin on intracerebroventricular (ICV) streptozotocin (STZ)-induced memory impairment in rats as evaluated in the Morris water maze test. STZ (ICV) treated rats had shown memory impairment along with a significant decrease in IR signaling molecules (IR, pIRS-1, pAkt, and pGSK-3α/β expression) and IDE expression in both hippocampus and cerebral cortex. Intranasal insulin delivery prevented these changes. Moreover, intranasal insulin was found to inhibit significantly glial cell activation (GFAP and Iba-1 expression), neuroinflammation (COX-2 expression, NFκB translocation, TNF-α, and IL-10 level) and amyloidogenic protein expression (BACE-1 and Aβ1-42 expression) in STZ (ICV)-injected rats. STZ (ICV)-induced caspase activation and postsynaptic neurotoxicity were also prevented by treatment with intranasal insulin. Our findings reveal that insulin has the neuroprotective effect and clearly signifies the potential use of intranasal insulin delivery for the treatment of AD. Graphical Abstract Neuroprotective effects of intranasal insulin administration on streptozotocin (ICV)-induced memory impairment in rats.

Transcranial magnetic stimulation to understand pathophysiology and as potential treatment for neurodegenerative diseases.

Common neurodegenerative diseases include Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). Transcranial magnetic stimulation (TMS) is a noninvasive and painless method to stimulate the human brain. Single- and paired-pulse TMS paradigms are powerful ways to study the pathophysiological mechanisms of neurodegenerative diseases. Motor evoked potential studied with single-pulse TMS is increased in PD, AD and ALS, but is decreased in HD. Changes in motor cortical excitability in neurodegenerative diseases may be related to functional deficits in cortical circuits or to compensatory mechanisms. Reduction or even absence of short interval intracortical inhibition induced by paired-pulse TMS is common in neurodegenerative diseases, suggesting that there are functional impairments of inhibitory cortical circuits. Decreased short latency afferent inhibition in AD, PD and HD may be related to the cortical cholinergic deficits in these conditions. Cortical plasticity tested by paired associative stimulation or theta burst stimulation is impaired in PD, AD and HD. Repetitive TMS (rTMS) refers to the application of trains of regularly repeating TMS pulses. High-frequency facilitatory rTMS may improve motor symptoms in PD patients whereas low-frequency inhibitory stimulation is a potential treatment for levodopa induced dyskinesia. rTMS delivered both to the left and right dorsolateral prefrontal cortex improves memory in AD patients. Supplementary motor cortical stimulation in low frequency may be useful for HD patients. However, the effects of treatment with multiple sessions of rTMS for neurodegenerative diseases need to be tested in large, sham-controlled studies in the future before they can be adopted for routine clinical practice.

Treatment Options in Alzheimer´s Disease: The GABA Story.

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Research focused on identifying compounds that restore cognition and memory in AD patients is a very active investigational pursuit, but unfortunately, it has been only successful in terms of developing symptomatic treatments. Aβ deposition and neurofibrillary tangles along with neuron and synapse loss are associated with neurotransmitter dysfunction and have been recognized as hallmarks of AD. Furthermore, clinical and preclinical studies point to this neurotransmitter dysfunction as a main factor underlying both cognitive and neuropsychiatric symptoms of the illness. Cholinergic deficit in AD prompted the use of cholinesterase inhibitors as the symptomatic treatment of cognitive decline in AD, however this therapeutic approach provides only modest benefit in the majority of patients. Hence, nowadays research is focused on investigating compounds that could restore cognition and memory in AD patients. GABA is the primary inhibitory neurotransmitter in the central nervous system and GABAergic neurons provide extensive innervation to cholinergic and glutamatergic neurons. It has been shown that dysfunction of the GABAergic system may contribute to cognitive impairment in humans. Significant reductions in GABA levels have been described in severe cases of AD, which could be underlying the behavioral and psychological symptoms of AD. This review examines the involvement of the GABAergic system in both cognitive and non-cognitive behavioural symptoms in AD, providing some pointers for rational drug development.

Emotion and Destination Memory in Alzheimer's Disease.

Research shows beneficial effect of emotion on self-related information in patients with Alzheimer's Disease (AD). Our paper investigates whether emotion improves destination memory (e.g., did I tell you about the manuscript?), which is thought to be self-related (e.g., did I tell you about the manuscript?). To this aim, twenty-seven AD patients and thirty healthy older adults told 24 neutral facts to eight neutral faces, eight positive faces, and eight negative faces. On a subsequent recognition task, participants had to decide whether they had previously told a given fact to a given face or not. Data revealed no emotional effect on destination memory in AD patients. However, in healthy older adults, better destination memory was observed for negative faces than for positive faces, and the latter memory was better than for neutral faces. The absence of emotional effect on destination memory in AD is interpreted in terms of substantial decline in this memory in the disease.

Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.

Serotonergic therapies for cognitive symptoms in Alzheimer's disease: rationale and current status.

Alzheimer's disease (AD) is the most common cause of dementia in elderly people. Research focused on identifying compounds that restore cognition and memory in AD patients is a very active investigational pursuit. Cholinesterase inhibitors for the symptomatic treatment of cognitive decline in AD have been in use for more than a decade but provide only modest benefits in most patients. Preclinical research is constantly providing new information on AD. The involvement of the serotonergic system in higher cognitive processes such as memory and learning has been widely described and extensive serotonergic denervation has been reported in AD. This review aims to explain the rationale behind testing serotonergic therapies for AD in terms of current knowledge about the pathophysiology of the disease. Based on preclinical studies, certain serotonin (5-HT) receptor ligands have been suggested to have the ability to modify or improve memory/cognition, specifically 5-HT receptors acting at 5-HT1A, 5-HT4 and 5-HT6 receptors. This article summarizes the pharmacology, efficacy, safety and tolerability data for the various serotonergic agents currently in clinical development for AD.

Effects of Lexical–Semantic Treatment on Memory in Early Alzheimer Disease

Background. Episodic memory and semantic abilities deteriorate early in Alzheimer disease (AD). Since the cognitive system includes interconnected and reciprocally influenced neuronal networks, the authors hypothesized that stimulation of lexical–semantic abilities may benefit semantically structured episodic memory. Objective. To investigate the effects of lexical–semantic stimulation (LSS) on verbal communication and episodic memory in early AD. Methods. Forty AD participants were randomized to LSS or unstructured cognitive stimulation (UCS) as control condition. Treatments lasted 3 months, 2 sections a week. The primary outcome measures were the Mini-Mental State Examination (MMSE), Boston Naming Test (BNT), Verbal Naming Test (VNT), Phonemic and Semantic Fluency, Story Recall, and Rey Auditory Verbal Learning (RAVL). Secondary outcome measures were neuropsychological tests assessing cognitive functions not stimulated by the intervention, such as attention, executive functions, and visual–spatial abilities, and the instrumental activities of daily living scale. A 6-month follow-up assessment was administered to the LSS group. Results. LSS treatment yielded significant improvements of the MMSE, BNT, VNT, Brief Story Recall, and RAVL delayed recall mean scores. Among secondary outcome measures, only working memory and the speed of a task assessing executive functions (Stroop test) improved after LSS. Unstructured cognitive stimulation intervention did not improve any cognitive domain. Six months after LSS discontinuation, the MMSE mean score remains significantly higher than the baseline value. Conclusion. LSS treatment may improve episodic memory in AD patients and may be regarded as a clinical option to counteract the cognitive decline typical of the disease.

Adverse effects of anticholinergic activity on cognitive functions in Alzheimer's disease

Elderly patients with Alzheimer's disease (AD) take more medicines, other than those for anti-dementia agents, than healthy people and are sensitive to anticholinergic medications. There are only a few reports, however, on the relationship between cognitive function and anticholinergic activity in AD patients, which is caused by taking prescribed medication. We measured serum anticholinergic activity (SAA) in 76 AD patients referred to a Psychogeriatric Unit and separated them into SAA positive group (n= 26, SAA (+) group) and SAA negative group (n= 50, SAA (-) group). The difference in demographic data and cognitive functions were compared between the two groups. The total scores of the Mini-Mental State Examination (MMSE), the score of MMSE domain of registration and recall were significantly lower (P < 0.05) and the Functional Assessment Staging (FAST) score, the number of different kinds of prescribed psychotropic medications (the number of prescribed psychotropic medications) were significantly higher (P < 0.05) in the SAA (+) group than in the SAA (-). These results suggest that a higher number of psychotropic medications prescribed leads to a tendency for SAA to be positive and that anticholinergic activity accelerates Alzheimer's pathology and decreases cognitive function, especially memory in AD patients. We should more prudently prescribe psychotropic medications to AD patients, because the prescribed psychotropic medications are one of the important causes of decline in cognitive function of AD patients by way of anticholinergic activity.

Distinct modulation of voltage‐gated and ligand‐gated Ca2+ currents by PPAR‐γ agonists in cultured hippocampal neurons

Type 2 diabetes mellitus is a metabolic disorder characterized by hyperglycemia and is especially prevalent in the elderly. Because aging is a risk factor for type 2 diabetes mellitus, and insulin resistance may contribute to the pathogenesis of Alzheimer's disease (AD), anti-diabetic agents (thiazolidinediones-TZDs) are being studied for the treatment of cognitive decline associated with AD. These agents normalize insulin sensitivity in the periphery and can improve cognition and verbal memory in AD patients. Based on evidence that Ca(2+) dysregulation is a pathogenic factor of brain aging/AD, we tested the hypothesis that TZDs could impact Ca(2+) signaling/homeostasis in neurons. We assessed the effects of pioglitazone and rosiglitazone (TZDs) on two major sources of Ca(2+) influx in primary hippocampal cultured neurons, voltage-gated Ca(2+) channel (VGCC) and the NMDA receptor (NMDAR). VGCC- and NMDAR-mediated Ca(2+) currents were recorded using patch-clamp techniques, and Ca(2+) intracellular levels were monitored with Ca(2+) imaging techniques. Rosiglitazone, but not pioglitazone reduced VGCC currents. In contrast, NMDAR-mediated currents were significantly reduced by pioglitazone but not rosiglitazone. These results show that TZDs modulate Ca(2+)-dependent pathways in the brain and have different inhibitory profiles on two major Ca(2+) sources, potentially conferring neuroprotection to an area of the brain that is particularly vulnerable to the effects of aging and/or AD.

Peripheral p70S6k levels and emotional memory in patients with Alzheimer's disease

Alzheimer's disease (AD) is clinically marked at the onset, by memory disturbances affecting explicit memory. Emotional explicit memory is enhanced in normal subjects and remained less affected at the beginning of AD. The kinase p70S6k participates in the control of protein translation and seems also implicated in the process of synaptic plasticity and the formation of memory at the molecular level. In a previous study, we have shown that peripheral p70S6k level is correlated with the decline of cognitive and memory functions in patients with AD. The goal of the present study was to analyse emotional and neutral explicit memory in AD patients and to evaluate the levels of active p70S6k in lymphocytes by western blots. The results reveal that the difference between emotional and neutral memories are correlated with the levels of peripheral p70S6k in patients with AD, as well as with the global cognitive scores assessed by the Mini Mental Status Examination. The decline of emotional memory in AD patients is reflected by the decrease of p70S6k levels.

Alzheimer's patients engage an alternative network during a memory task

We conducted an event-related functional magnetic resonance imaging experiment to better understand the potentially compensatory alternative brain networks activated by a clinically relevant face-name association task in Alzheimer's disease (AD) patients and matched control subjects. We recruited 17 healthy subjects and 12 AD patients at an early stage of the disease. They underwent functional magnetic resonance imaging scanning in four sessions. Each of the sessions combined a "study" phase and a "test" phase. Face/name pairs were presented in each study phase, and subjects were asked to associate faces with names. In the test phase, a recognition task, faces seen in the study phase were presented each with four different names. The task required selection of appropriate previously associated names from the study phase. Responses were recorded for post hoc classification into those successfully or unsuccessfully encoded. There were significant differences between the groups in accuracy and reaction time. Comparison of correctly versus incorrectly encoded and recognized pairs in the two groups indicated bilateral hippocampal hypoactivation both when encoding and recognizing in the AD group. Moreover, patients showed bilateral hyperactivation of parts of the parietal and frontal lobes. We discuss whether hyperactivation of a frontoparietal network reflects compensatory strategies for failing associative memory in AD patients.

Effects of Alzheimer disease on memory for verbal emotional information

In healthy young and older adults, emotional information is often better remembered than neutral information. It is an open question, however, whether emotional memory enhancement is blunted or preserved in Alzheimer disease (AD). Prior studies of emotional memory in AD have included small samples of patients. In addition, studies that failed to find an enhancement effect in AD used stimuli lacking semantic coherence (e.g. lists of unrelated words, some that were emotional and others that were neutral). To circumvent these limitations, the present study examined a large number of AD patients ( N=80) and investigated whether AD patients would show better memory for a verbal description of an emotional event as compared to a neutral one. AD patients were equivalent to young and older control participants in rating the emotional descriptions for valence and arousal. Unlike the control groups, however, memory in AD patients did not benefit from the emotional narratives. We conclude that AD disrupts memory enhancement for at least some types of verbal emotional information.

Loss of Financial Capacity in Alzheimer's Disease: The Role of Working Memory

Recent research has demonstrated that loss of financial capacity is a common consequence of Alzheimer's disease (AD). While progressive cognitive decline is a defining feature of AD, the relationship between such decline and loss of financial capacity in AD remains unclear. Working memory may be strongly associated with financial abilities, as many financial tasks require temporary storage and manipulation of numerical and other data. The present study examined the relationship between financial capacity and working memory in AD patients. Participants included 20 AD patients and 23 cognitively intact older controls. Working memory was conceptualized using Baddeley and colleagues' model, which posits that the three components of the working memory system are the visuospatial sketchpad, phonological loop, and central executive system. The present study examined only the latter two components of working memory. Each participant was administered the Financial Capacity Instrument (FCI), an instrument that directly assesses eight domains of financial activity, and the WAIS-III Working Memory subtests (Digit Span, Arithmetic, Letter–Number Sequencing). AD patients as a group performed significantly below controls on the FCI Total Score and on each of the eight FCI domains and working memory subtests. Within the AD group, measures of the central executive component of working memory (WAIS-III Digits Backward, Arithmetic, and Letter-Number Sequencing tests) showed strong correlations with the FCI domains of basic monetary skills, checkbook management, bank statement management, and bill payment and FCI total score, while a measure of the phonological loop component of working memory (WAIS-III Digits Forward) was not significantly correlated with any FCI domains or with the FCI total score. The results suggest that the multiple domains of financial capacity are primarily correlated with the central executive component of working memory.

The acetylcholinesterase inhibitor, ENA 713 (Exelon), attenuates the working memory impairment induced by scopolamine in an operant DNMTP task in rats.

The disruption of working memory in the delayed non-matching to position (DNMTP) task by the muscarinic antagonist, scopolamine, is considered to be a model of the spatial working memory deficit in Alzheimer's disease (AD) patients. To investigate whether ENA 713 (Exelon) (0.1, 0.5 mg/kg, IP), an acetylcholinesterase inhibitor, would reverse the effects of scopolamine in the DNMTP task. Male Lister Hooded rats were trained to criterion in an operant DNMTP task (0- to 16-s delay intervals) before receiving vehicle, scopolamine (0.05 mg/kg, SC) alone, ENA 713 (0.1, 0.5 mg/kg, IP) alone, or combinations of scopolamine and ENA 713, in two variations of the task - with and without barriers inserted between the food magazine and the two levers. Barriers were inserted to prevent the use of positional strategies to perform the task, since this behaviour may confound the conclusions of the effect of drugs on working memory. It was found that: (i) scopolamine significantly reduced choice accuracy delay-dependently in both test situations while modifying non-mnemonic measures of task performance delay-independently, indicating an impairment of working memory; (ii) ENA 713 (0.5 mg/kg) significantly attenuated the scopolamine-induced impairment of working memory and significantly reduced the scopolamine-induced changes in some non-mnemonic measures of task performance; (iii) the presence of barriers did not alter the effects of scopolamine and ENA 713 on working memory. ENA 713 reversed the working memory deficit induced by scopolamine. These results are consistent with the attenuation of learning and memory disruptions due to cholinergic dysfunction by ENA 713 in other preclinical assays, and predict a drug-induced improvement in working memory in AD patients.