Memory deficits in Alzheimer's disease: the encoding hypothesis and cholinergic function

Forgetting functions generated by delayed matching-to-sample procedures allow delay-dependent effects to be distinguished from delay-independent effects on working memory. Parameters of negative exponential functions estimate initial discriminability (intercept) and rate of forgetting (slope). Forgetting functions for patients with Alzheimer's disease indicate that they differ from normal controls in terms of reduced initial discriminability—that is, in the encoding component of memory performance— but not convincingly in rate of forgetting. Reanalyses of previous studies with different species suggest that pro- and anticholinergic drugs influence initial discriminability in delayed matching-to-sample performance, but not rate of forgetting. The results of our reanalyses are consistent with the conclusion that the cholinergic system plays a role in the encoding component of working memory and that this is the main characteristic of the memory deficit shown by patients with Alzheimer's disease.     

Nicotine and sensory memory in Alzheimer's disease: an event-related potential study

The auditory mismatch negativity (MMN) event-related brain potential (ERP) reflects the storage of information in acoustic sensory memory. Thirteen patients with probable Alzheimer's disease (AD), 6 receiving treatment with the cholinesterase inhibitor (ChEI) tacrine (tetrahydroaminoacridine, THA) and 7 receiving no treatment, were administered 2 mg of nicotine polacrilex and placebo. MMNs were recorded with 1- and 3-s interstimulus intervals pre- and postplacebo/nicotine administration. In nontreated patients, amplitudes were decreased from pre- to postplacebo recordings but remained stable in THA-treated patients. Comparison of pre- and postnicotine MMNs found amplitude increases with nicotine in nontreated but not THA-treated patients. MMN latencies were shortened by nicotine in both treatment groups. These exploratory findings suggest that nicotine-improved strength of acoustic sensory memory traces and speed of acoustic sensory discrimination in AD are differentially affected by chronic ChEI treatment.     

Dysnomia in Alzheimer's disease: an evaluation of neurobehavioral subtypes.

The relative influence of perceptual and semantic features on naming performance was investigated with reference to the neurobehavioral profiles displayed by patients with Alzheimer's disease (AD). Forty-one patients were classified as manifesting a verbal, visual, or global subtype based upon their pattern of neuropsychological functioning. Perceptual characteristics of to-be-named pictures were varied by manipulating the amount of line detail, whereas semantic qualities were varied by altering word frequency norms. All AD subtypes were less accurate than normal elderly controls in naming low frequency pictures. Patients and controls took longer to name low frequency and high complexity pictures, and this effect was comparable across the AD groups. Patients with predominantly visual deficits were significantly slower in naming than controls, and those with verbal impairments made a higher proportion of semantic naming errors when compared to patients displaying visual or severe global impairments. These results suggest that deficits in semantic processing contribute to naming dysfunction in AD, and they highlight the importance of examining dissociations among neurobehavioral subtypes.     

Visual awareness and the levels of processing hypothesis: A critical review

Does a visual percept emerge to consciousness in a graded manner (i.e. evolving through increasing degrees of clarity), or according to a dichotomous, “all-or-none” pattern (i.e. abruptly transitioning from unawareness to awareness)? The level of processing hypothesis (LoP; B. Windey and A. Cleeremans, 2015) recently proposed a theoretical framework where the transition from unaware to aware visual experience is graded for low-level stimulus representations (i.e. stimulus “energy” or “feature” levels) whereas it is dichotomous for high-level (i.e. the perception of “letters”, “words” or “meaning”) stimulus perception. Here, we will critically review current behavioral and brain-based evidence on the LoP hypothesis and discuss potential challenges (such as differences in LoP conceptualizations, awareness scale related issues, attentional confounds and divergences on experimental factors or statistical analyses) which might be of use for future research within the field. Overall, the LoP hypothesis is a recent and promising proposal that attempts to integrate divergent evidence on the graded vs. dichotomous emergence of awareness debate. Whereas current evidence validates some of the assumptions proposed by the LoP account, there is still much work to do on both methodological and experimental levels. Future neuroimaging studies might help to disentangle the current complex pattern of results found in LoP studies and, importantly, shed some light on the ongoing debate about the search for the Neural Correlates of Consciousness (NCC).     

Emerging therapeutics for Alzheimer's disease: an avenue of hope

Emerging therapies for Alzheimer's disease offer hope to patients and their caregivers. Future treatments will probably include combination approaches with agents that modify amyloid processing, deposition, and clearance. One example, the AD vaccine, reduced amyloid burden and changed behavior in animal models of AD, but the human trial was halted when several subjects developed brain inflammation. Anti-inflammatory agents have epidemiologic support, but clinical trials have been disappointing, possibly related to inadequate study with anti-inflammatory agents that modify amyloid processing. Agents that target known cardiovascular risk factors, such as hypercholesterolemia, hypertension, and insulin resistance, have epidemiologic, preclinical, and clinical evidence to warrant further investigation. Heavy metal chelators, antioxidants, neurotrophic factors, glutaminergic modulators, and agents that modify hyperphosphorylation of Tau are other approaches in research and development.     

Preservation of categorical knowledge in Alzheimer's disease: A computational account

Abstract

The distinction between knowledge of specific exemplars and knowledge of their general categories is central to much theorising on the nature of semantic memory. The dissociation between exemplar and category knowledge observed in Alzheimer's Disease (AD) would appear to support this distinction, and to suggest that different neural systems are involved in the representation of exemplar and category knowledge. We review the evidence for preserved category knowledge in the semantic memory impairment of AD, and propose an alternative interpretation, according to which category and exemplar knowledge are both represented in the same distributed neural substrate. The relative preservation of category knowledge is a consequence of the greater frequency, and hence greater robustness, of the representation of attributes shared by all or most members of a category, compared to exemplar-unique attributes. We test and confirm the computational adequacy of this hypothesis in two computer simulations.     

Alzheimer's disease in Down syndrome: neurobiology and risk

Down syndrome (DS) is characterized by increased mortality rates, both during early and later stages of life, and age-specific mortality risk remains higher in adults with DS compared with the overall population of people with mental retardation and with typically developing populations. Causes of increased mortality rates early in life are primarily due to the increased incidence of congenital heart disease and leukemia, while causes of higher mortality rates later in life may be due to a number of factors, two of which are an increased risk for Alzheimer's disease (AD) and an apparent tendency toward premature aging. In this article, we describe the increase in lifespan for people with DS that has occurred over the past 100 years, as well as advances in the understanding of the occurrence of AD in adults with DS. Aspects of the neurobiology of AD, including the role of amyloid, oxidative stress, Cu/ZN dismutase (SOD-1), as well as advances in neuroimaging are presented. The function of risk factors in the observed heterogeneity in the expression of AD dementia in adults with DS, as well as the need for sensitive and specific biomarkers of the clinical and pathological progressing of AD in adults with DS is considered.     

A gandhian model of health: Looking at Alzheimer's disease

Mahatma Gandhi was often criticized for mixing religion, politics, economics, and health. However, it was his very insistence on the fundamental interrelationship of all aspects of life that gives his ideas such relevance for today's problems. This paper focuses on his views on health and attempts to develop a Gandhian model of health that has relevance for us today. This model is then specifically applied to the vexing problem of Alzheimer's disease, and an ongoing therapeutic trial that is based on this model is described.     

Metaphor comprehension in Alzheimer's disease: novelty matters

The comprehension of non-literal language was investigated in 20 probable Alzheimer's disease (pAD) patients by comparing their performance to that of 20 matched control subjects. pAD patients were unimpaired in the comprehension of conventional metaphors and idioms. However, their performance was significantly lower in the case of non-conventional (novel) metaphor comprehension. This ability was not related to global cognitive deterioration or to deficits in the cognitive domains of attention, memory and language comprehension. On the other hand, the impairment in verbal reasoning appeared to be relevant for both novel and conventional metaphor comprehension. The relationship between novel metaphor comprehension and performance in the visual-spatial planning task of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) suggests that executive impairment, possibly related to prefrontal dysfunction, may be responsible for the pAD patients' poor performance in novel metaphor comprehension. The present findings suggest a role of the prefrontal cortex in novel metaphor comprehension.     

Projective identification: an alternative hypothesis

The concept of projective identification as a primitive defense mechanism is reassessed. An alternative hypothesis is offered: that projective identification can best be understood as a compromise formation which includes as its major component an "identification with the aggressor" or a "turning of passive into active." This reversal is demonstrated within a two-tiered transference/countertransference of the analyst as powerful parent and the patient as the helpless child. On the deeper level the patient enacts the role of dominant parent and the analyst experiences the feelings which the patient had felt as a child.     

Serum cholesterol levels and suicide: a meta-analysis

A meta-analysis was performed on studies exploring the link between low levels of serum cholesterol and increased risk of suicide. Follow-up studies found that those with lower cholesterol levels do have a tiny but statistically significant increased risk of completing suicide. Individuals who have attempted suicide in the past have lower cholesterol levels, especially if they used violent methods for suicide. Cholesterol lowering studies, however, did not lead to a significant increase in completed suicide.     

Autism and the amygdala: an endocrine hypothesis

Children become oriented to the world, in part, by coming to understand something of the experiences of others. The facial expressions that people make are an avenue for understanding something about them, as are the diverse forms of bodily responses emitted and interpreted by individuals. People with autism often find bodily communications to be aversive, thereby limiting what they can learn from others during social interactions. The amygdala is an important area of the brain, amongst others, for integrating the internal milieu with the social ambiance. Individuals with autism consistently demonstrate dysregulation of amygdala function. Diverse regions of the amygdala, which contain neuropeptides, figure in the appraisal systems that underlie behavioral approach and avoidance responses. One neuropeptide linked to social recognition and approach behaviors is oxytocin (which is known to be decreased in autistic individuals) and another neuropeptide corticotropin releasing hormone is tied to avoidance behaviors. A neuroendocrine hypothesis is suggested to account for some of the features associated with autism.     

Excess disability and malignant social psychology: A case study of Alzheimer's disease

An in-depth case study was undertaken to assess the effects of what Kitwood has termed ‘malignant social psychology’ on the observed behaviour of an Alzheimer's disease sufferer. Interviews were conducted with the spouse and observations were made in an adult day-care centre, where staff members were also interviewed. Abilities that the spouse reported to be absent at home were readily observed at the day-care centre, lending support to Brody's idea of excess disability, i.e. disability not due to disease alone. Furthermore, forms of malignant social psychology existed in the home environment but did not exist in the day-care centre. Excess disability and its absence coincided with the presence and absence of aspects of malignant social psychology. The sufferer's behaviour was found to be affected not only by the extant neuropathology, but also by social relationships.     

Semantic memory in Alzheimer's disease

Patients with Alzheimer's disease have been suggested to have a semantic memory impairment not present in the normal old. This article reviews the performance of Alzheimer patients on tests of various aspects of semantic memory, including word finding, knowledge of the semantic attributes, and associates of concepts, as well as their category membership. The effect that semantic context has on cognitive processes such as lexical and semantic priming and memory encoding is also reviewed. Finally, the ability of theoretical constructs such as implicit memory and automaticity to explain intertask variability in Alzheimer patients' semantic performance is discussed.     

Maze learning in Alzheimer's disease

Alzheimer's disease (AD) patients and normal elderly controls performed a block of 10 trials on a finger maze, followed by a 45-min period during which verbal learning measures were administered. Subjects then performed an additional 10 trials on the original maze, followed by 10 trials on a new maze. The AD patients and a subset of control subjects decreased mean completion time across Blocks 1 and 2, suggesting skill acquisition. Mean time on Block 3 was significantly less than mean time on Block 1, suggesting skill generalization. A subset of controls did not show the above pattern. The results of this study suggest that AD patients are able to acquire and generalize a cognitively mediated perceptual-motor skill.     

Posture recognition in Alzheimer's disease

BACKGROUND: Apraxia is neurologically induced deficit in the ability perform purposeful skilled movements. One of the most common forms is ideomotor apraxia (IMA) where spatial and temporal production errors are most prevalent. IMA can be associated Alzheimer's disease (AD), even early in its course, but is often not identified possibly because the evaluation of IMA by inexperienced judges using performance tests is unreliable. The purpose of this study, therefore, is to learn if the Postural Knowledge Test (PKT), a praxis discrimination test that assesses knowledge of transitive (PKT-T subtest) and intransitive (PKT-I subtest) postures and does not require extensive training, is as sensitive and specific as the praxis performance tests. METHODS: We studied 15 subjects with probable AD as well as 18 age-matched controls by having them perform transitive and intransitive gestures to command and imitation, as well as having them discriminate between correct and incorrect transitive and intransitive postures. RESULTS: Overall on all tests, the control subjects performed better than those with AD. In addition all subjects had more trouble with transitive than intransitive gestures. Using a stepwise discriminative analysis, 81.8% of the subjects could be classified according to Group (94.4% of Controls, 66.7% of AD subjects). In this analysis, the PKT-T (transitive posture subtest) was the only measure that contributed to the discrimination of subjects. CONCLUSION: We found that having subjects select the correct transitive hand postures in this "booklet test" was more sensitive than grading their praxis performances even when using judges with extensive training. This suggests that this discrimination test might be an excellent means for diagnosing and screening patients for AD. The reason why recognition of transitive postures is relatively more difficult for our AD subjects is not known. Two possibilities are that the representations for intransitive movements are stronger than those for transitive movements, and hence, more resistant to degradation, or that intransitive acts are stored in parts of the brain not affected by AD.     

Factor structure and aetiological architecture of the BRIEF: A twin study

Executive function is a broad construct that encompasses various processes involved in goal‐directed behaviour in non‐routine situations (Banich, 2009). The present study uses a sample of 560 5‐ to 16‐year‐old twin pairs (M = 11.14, SD = 2.53): 219 monozygotic twin pairs (114 female; 105 male) and 341 dizygotic twin pairs (136 female, 107 male; 98 opposite sex) to extend prior literature by providing information about the factor structure and the genetic and environmental architecture of the Behavior Rating Inventory of Executive Function (BRIEF; Gioia et al., 2000, Child Neuropsychol., 6, 235; Gioia et al., 2000, Behavior rating inventory of executive function, Lutz, FL: Psychological Assessment Resources), a multifaceted rating scale of everyday executive functions. Phenotypic results revealed a 9‐scale, 3‐factor model best represents the BRIEF structure within the current sample. Results of the genetically sensitive analyses indicated the presence of rater bias/contrast effects for the Initiate, Working Memory, and Task‐Monitor scales. Additive genetic and non‐shared environmental influences were present for the Initiate, Plan/Organize, Organization of Materials, Shift, and Monitor and Self‐Monitor scales. Influences on Emotional Control were solely environmental. Interestingly, the aetiological architecture observed was similar to that of performance‐based measures of executive function. This observed similarity provided additional evidence for the usefulness of the BRIEF as a measure of ‘everyday’ executive function.     

Confabulation in Alzheimer's disease.

Confabulation is present when memory is disturbed, but does it occur in Alzheimer's disease (AD) where memory abnormalities are often severe? In this study, confabulation was assessed prospectively in 26 AD patients and 15 normal elderly (NE) controls using a neuropsychological battery specifically designed to assess different types of memory errors. The results indicated that the AD group made significantly more verbal intrusions than the NE group. These findings provide evidence for the feasibility of eliciting confabulatory-type behavior during clinical assessment and support previous reports which have documented verbal intrusions as a common accompaniment of the memory impairment manifested by AD patients.     

Social anxiety disorder in children and youth: A research update on aetiological factors

Social Anxiety Disorder (SAD) is a heterogeneous and distressing problem for many children and youth. This review focuses on the etiology and maintenance of SAD, and examines research findings in several key areas of investigation: genetic or hereditary factors (twin and family studies), temperament characteristics (behavioural inhibition), and parent–child interactions (attachment, parenting styles). It is concluded that genetic influences, behavioural inhibition, and parent–child interactions play significant and interactive roles in the development and maintenance of SAD. Other influences such as peer relationships, social skills deficits, and traumatic experiences are also acknowledged. Ultimately, an understanding of such pathways should facilitate effective early screening and intervention of children at risk for severe social anxiety.