Subjective aspects of cognitive control at different stages of processing

Although research on cognitive control has addressed the effects that different forms of cognitive interference have on behavior and the activities of certain brain regions, until recently, the effects of interference on subjective experience have not been addressed. We demonstrate that, at the level of the individual trial, participants can reliably introspect the subjective aspects (e.g., perceptions of difficulty, competition, and control) of responding in interference paradigms. Similar subjective effects were obtained for both expressed and unexpressed (subvocalized) actions. Few participants discerned the source of these effects. These basic findings illuminate aspects of cognitive control and cognitive effort. In addition, these data have implications for the study of response interference in affect and self-control, and they begin to address theories regarding the function of consciousness.     

Increased cognitive load leads to impaired mobility decisions in seniors at risk for falls

Successful mobility requires appropriate decision-making. Seniors with reduced executive functioning-such as senior fallers-may be prone to poor mobility judgments, especially under dual-task conditions. We classified participants as "At-Risk" and "Not-At-Risk" for falls using a validated physiological falls-risk assessment. Dual-task performance was assessed in a virtual reality environment where participants crossed a simulated street by walking on a manual treadmill while listening to music or conversing on a phone. Those "At-Risk" experienced more collisions with oncoming cars and had longer crossing times in the Phone condition compared to controls. We conclude that poor mobility judgments during a dual-task leads to unsafe mobility for those at-risk for falls.     

Focused attention deficits in patients with Alzheimer's disease and mild cognitive impairment

Reaction time (RT) tasks take various forms, and can assess psychomotor speed, (i.e., simple reaction time task), and focused attention (i.e., choice reaction time (CRT) task). If cues are provided before stimulus presentation (i.e., cued choice reaction time (CCRT) task), then a cueing effect can also be assessed. A limited number of studies have addressed the nature of focused attention impairments in Alzheimer's disease (AD). Additionally, it is unknown whether similar impairments occur in Mild Cognitive Impairment (MCI). The current study used three RT tasks to address the nature of focused attention impairments in AD and MCI subjects. The results suggest that there were significant CRT and CCRT differences in AD subjects when compared to NECs. Furthermore, slowed RTs were also present in the MCI group, which provides evidence for impaired focussed attention and the inability to benefit from a cue in both the MCI and AD groups. The implications of the impairments related to the MCI group could potentially prove useful in early diagnosis of cognitive impairments in the elderly.     

Proper names in the early stages of Alzheimer's disease

A short proper name retrieval test was found to discriminate between unselected subjects and age- and education- matched patients affected by Alzheimer's type dementia at a stage where the Mini-Mental State Examination could not detect a difference between these groups. The proper name retrieval task also compared favorably with the 3MS, a more sensitive, modified version of the MMSE. These findings suggest that proper name retrieval could be used to an advantage and become a routine component of short batteries for the early detection of Alzheimer's disease.     

Functional decline in the early stages of Alzheimer's disease

At present most reports of functional decline in patients with Alzheimer's Disease (AD) are anecdotal, and few studies have objectively documented the course of the disease. This is a report of a 2-year follow-up of 15 AD patients characterized by mild functional impairment, and 22 age-, sex-, and education-matched control subjects. In a previous cross-sectional study of these 37 subjects and 16 AD patients with moderate functional impairment, we found that measures of memory and attention deficits accounted for much of the impairment observed in functional competence. The current longitudinal study found that these same initial assessments could be used to predict functional decline in the 15 mildly impaired patients. These patients were observed to decline to levels similar to those of the 16 moderate patients. In contrast, the control subjects exhibited little decline during the same period. These results both affirm that it is possible to diagnose AD in its mild form and demonstrate the validity of the initial diagnosis.     

The Tower of London Test: different scoring criteria for diagnosing Alzheimer's disease and mild cognitive impairment

The Tower of London (TOL) is used for evaluating planning skills, which is a component of the executive functions. Different versions and scoring criteria were developed for this task, and some of them present with different psychometrical properties. This study aimed to evaluate two specific scoring methods of the TOL in diagnosing Mild Cognitive Impairment and probable Alzheimer's disease. The TOL total scores from 60 patients of each diagnosis were compared with the performance of 60 healthy-aged controls using receiver operating characteristics analysis and multinomial logistic regression. Krikorian method better diagnosed Alzheimer's disease, while Portellas's was better at discriminating healthy controls from Mild Cognitive Impairment, but were not efficient at comparing this last group with Alzheimer's patients. Regression analysis indicates that in addition to screening tests, TOL improves the classification of the three groups. The results suggest the two scoring methods used for this task may be useful for different diagnostic purposes.     

Movements execution in amnestic mild cognitive impairment and Alzheimer's disease

We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD.     

Studies of implicit prototype extraction in patients with mild cognitive impairment and early Alzheimer's disease

Studies of incidental category learning support the hypothesis of an implicit prototype-extraction system that is distinct from explicit memory (Smith, 2008). In those studies, patients with explicit-memory impairments due to damage to the medial-temporal lobe performed normally in implicit categorization tasks (Bozoki, Grossman, & Smith, 2006; Knowlton & Squire, 1993). However, alternative interpretations are that (a) even people with impairments to a single memory system have sufficient resources to succeed on the particular categorization tasks that have been tested (Nosofsky & Zaki, 1998; Zaki & Nosofsky, 2001) and (b) working memory can be used at time of test to learn the categories (Palmeri & Flanery, 1999). In the present experiments, patients with amnestic mild cognitive impairment or early Alzheimer's disease were tested in prototype-extraction tasks to examine these possibilities. In a categorization task involving discrete-feature stimuli, the majority of subjects relied on memories for exceedingly few features, even when the task structure strongly encouraged reliance on broad-based prototypes. In a dot-pattern categorization task, even the memory-impaired patients were able to use working memory at time of test to extract the category structure (at least for the stimulus set used in past work). We argue that the results weaken the past case made in favor of a separate system of implicit prototype extraction.     

Predictors of cognitive change from preclinical to clinical Alzheimer's disease

We examined individual-difference variables in relation to the rate of change in global cognitive performance, measured by the MMSE, from 3 years prior to diagnosis of Alzheimer's disease (AD) to the time of diagnosis. The population-based sample consisted of 230 incident AD persons who were followed over a 3-year interval. The average annual decline in MMSE was 1.81 points. Being older and acquiring additional diseases during the 3 years preceding diagnosis predicted a faster rate of decline in global cognitive functioning. However, other individual difference variables such as sex, education, depression, vitamin levels (vitamin B12 and folic acid), apolipoprotein status, and social network did not precipitate the rate of decline in the preclinical phase of AD.     

Hippocampal metabolites and memory performances in patients with amnestic mild cognitive impairment and Alzheimer's disease

In patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), previous studies have reported the decrease of N-acetylaspartate (NAA) concentration and the increase of myo-inositol (MI) concentration using proton magnetic resonance spectroscopy (1H-MRS). However, it remains to be investigated what aspects of cognition these metabolite changes reflect. In this study we evaluated the correlations between the subtests of Wechsler Memory Scale-Revised (WMS-R) and the concentrations of NAA and MI. The study group was composed of 42 patients with aMCI and 67 patients with AD. 1H-MR spectra with a single voxel-point resolved spectroscopy (PRESS) at a short echo time were acquired from the bilateral hippocampi and posterior cingulate gyrus. Positive correlations were shown between the NAA concentration in the left hippocampus and verbal memory, visual memory, general memory, attention and delayed recall; and furthermore, between the NAA concentration in the right hippocampus and verbal memory and general memory. Negative correlations were shown between the MI concentration in the left hippocampus and verbal memory, general memory, and delayed recall, and between the MI concentration in the right hippocampus and verbal memory. There was no significant correlation between any subtest of WMS-R and these two metabolite concentrations in the posterior cingulate gyrus. These findings suggest that bilateral, especially left hippocampal NAA and MI concentrations are associated with memory dysfunction observed in patients with aMCI and AD. In contrast, NAA and MI concentrations in the posterior cingulate gyrus may be less related to memory function than those in the hippocampus.     

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.     

Different patterns of cognitive slowing produced by Alzheimer's disease and normal aging

Aging has previously been shown to produce a generalized proportional slowing of all cognitive operations. In contrast, the present results suggested that Alzheimer's disease produces a disproportionate reduction in the speed with which patients carry out one or more mental operations. The tasks that demented patients found particularly difficult involved either a self-directed search of their lexicon or the use of familiarity information.     

A comparison of the category fluency deficits associated with Alzheimer's and Huntington's disease

The supermarket verbal fluency test of the Dementia Rating Scale (DRS) was administered to 20 patients with mild Alzheimer's disease (Mi-DAT), 20 patients with moderately severe Alzheimer's disease (Mo-DAT), 20 patients with Huntington's disease (HD), and 40 normal control subjects. The findings confirmed previous reports that Mo-DAT patients retrieved fewer words per category of supermarket items sampled and had a greater propensity to generate category labels (superordinates) than did intact controls. Similar disruptions of the structure of semantic knowledge were also noted in the fluency performances of the Mi-DAT and HD patients. The Mi-DAT patients' tendency to generate few exemplars for each category sampled suggested that a significant disruption in the structure of semantic knowledge occurred even in the earliest stages of DAT. When the present fluency findings for the HD patients were considered with previous reports of linguistic changes in this disorder, it appeared that HD patients' deterioration in semantic knowledge involved associative changes rather than the bottom-up breakdown associated with DAT.     

The usefulness of the story recall test in patients with mild cognitive impairment and Alzheimer's disease

ABSTRACT

Background: The story recall test (SRT) is one of the most reliable neuropsychological assessments for evaluating verbal memory function in order to distinguish between individuals with normal aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD). The SRT is analogous to the logical memory test in Wechsler Memory Scale-III, which has recently been developed and standardized to apply to older adults in Korea. The purpose of this study was to examine the usefulness of the SRT and its ability to discriminate between normal cognitive aging and patients with MCI or AD. Methods: One hundred and twelve patients with MCI, 97 patients with AD, and 53 healthy elderly adults participated in this study. The SRT was compared with the Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), Korean version of the Mini Mental State Examination (K-MMSE), and the Korean version of the Hopkins Verbal Learning Test (K-HVLT). Results: The SRT was well-correlated with the dementia rating scales and the K-HVLT. However, the sensitivity and specificity of the SRT was greatly influenced by the level of education of the subjects. Conclusions: The SRT is a sensitive measurement of verbal memory function that can be used in clinical settings to discriminate between normal memory functioning and the very early and moderate stages of AD in a Korean population. Moreover, it is important to recognize that the SRT is more appropriate for subjects with a high level of education rather than a low level of education to differentiate normal cognitive aging from MCI or AD.     

The role of cardiovascular risk factors in Alzheimer's disease

The distinction between Alzheimer's disease and vascular dementia, the two most common types of dementia, has been undermined by recent advances in epidemiologic, clinical, imaging, and neuropathological studies. Cardiovascular risk factors, traditionally regarded as distinguishing criteria between the two entities, have been shown to be associated with both AD and vascular dementia. In this article, we propose mechanisms of action of cardiovascular risk factors in AD, suggest possible explanations for the overlap with vascular dementia and discuss the implications this might have on future differential diagnosis, research, and treatment strategies.     

Alzheimer's disease patients' cognitive status and course years prior to symptom recognition

This is a prospective examination of the cognitive performance and cognitive course of persons in an asymptomatic "preclinical" phase who eventually developed Alzheimer's disease (AD). We compared performances on the Mayo Cognitive Factor Scales (MCFS) of 20 persons in a neurologically normal cohort who subsequently developed AD to the performances of 60 persons who remained free of dementia symptoms. For the AD patients, exams occurred prior to the appearance of dementia symptoms (an average of 4.2 and 1.5 years prior to symptom onset). Results reveal strong group differences on learning and retention, with eventual AD patients scoring lower than controls years prior to reporting symptoms of the disease. There was no significant interaction effect (group x testing session) for memory retention, suggesting that memory decline in this preclinical period may be too slow to be a useful indicator of future AD. A significant interaction (but no group effect) was seen for verbal comprehension.     

Person-specific paths of cognitive decline in Alzheimer's disease and their relation to age

Change in global and specific measures of cognitive function was studied in a cohort of 410 persons with Alzheimer's disease. Persons completed up to 5 annual evaluations; follow-up participation among survivors exceeded 90%. Average annual decline was 0.57 standard score units (95% confidence interval [CI]: -0.51 to -0.62) on a composite measure based on 17 individual tests and 3.26 points (95% CI: -3.06 to 3.46) on the Mini-Mental State Examination, but substantial heterogeneity was apparent. On both global and specific measures, rate of cognitive decline was reduced in older persons compared with younger persons. A similar effect was observed for estimated age of disease onset. The effect of age was approximately linear and was not attributable to education, sex, race, other conditions that impair cognition, or mortality. The results indicate that person-specific paths of cognitive decline in Alzheimer's disease vary substantially and suggest that in clinical settings some of this variability is related to age.