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.     

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.     

Syntactic comprehension deficits in Alzheimer's disease

Syntactic comprehension of German patients with dementia of the Alzheimer type was investigated and compared to healthy controls matched with respect to age, sex, and education. Special attention was directed at syntactic structures, which, in contrast to a language like English, are feasible in a grammatically rich language like German. In a sentence picture matching paradigm, only semantically reversible sentences were used. Syntactic complexity ranged from simple active voice sentences to more complex sentences like center-embedded object relative sentences. In comparison to their controls, patients showed a deficit in nearly all categories. Their performance was not influenced by age, but was heavily influenced by the degree of cognitive impairment. Patients with mild cognitive impairment, as defined by a MMSE score of 20 or higher, showed only slight difficulties in syntactic processing, whereas patients with moderate to severe impairment (MMSE < 20) did not perform above chance limits in most syntactic categories. It appears as though syntactic comprehension is only mildly affected in the early stages of Alzheimer's disease and is rather severely impaired in more advanced stages. In the present report, results are discussed in terms of working memory demands for syntactic processing.     

Visuo-spatial imagery impairment in posterior cortical atrophy: a cognitive and SPECT study

This study investigated the cognitive profile and the cerebral perfusion pattern in a highly educated 70 year old gentleman with posterior cortical atrophy (PCA). Visuo-perceptual abilities, spatial memory, spatial representation and navigation, visuo-spatial mental imagery, semantic and episodic-autobiographical memory were assessed. Regional cerebral blood flow (rCBF) was imaged with SPECT. Cognitive testing showed visual-perceptual impairment, apperceptive visual and landmark agnosia, topographical disorientation with way-finding deficits, impaired map learning and poor mental image generation. Semantic memory was normal, while episodic-autobiographical memory was impaired. Reduced rCBF was found mainly in the right hemisphere, in the precentral gyrus, posterior cingulate and middle temporal gyri, cuneus and precuneus, in the left superior temporal and lingual gyri and in the parahippocampus bilaterally. Hypoperfusion in occipito-parietal regions was associated with visuo-spatial deficits, whereas deficits in visuo-spatial mental imagery might reflect dysfunction related to hypoperfusion in the parahippocampus and precuneus, structures which are responsible for spatial and imagery processing. Dissociating performance between preserved semantic memory and poor episodic-autobiographical recall is consistent with a pattern of normal perfusion in frontal and anterior temporal regions but abnormal rCBF in the parahippocampi. The present findings indicate that PCA involves visuo-spatial imagery deficits and provide further validation to current neuro-cognitive models of spatial representation and topographical disorientation.     

Verb deficits in Alzheimer's disease and agrammatism: implications for lexical organization

This study examined the nature of verb deficits in 14 individuals with probable Alzheimer's Disease (PrAD) and nine with agrammatic aphasia. Production was tested, controlling both semantic and syntactic features of verbs, using noun and verb naming, sentence completion, and narrative tasks. Noun and verb comprehension and a grammaticality judgment task also were administered. Results showed that while both PrAD and agrammatic subjects showed impaired verb naming, the syntactic features of verbs (i.e., argument structure) influenced agrammatic, but not Alzheimer's disease patients' verb production ability. That is, agrammatic patients showed progressively greater difficulty with verbs associated with more arguments, as has been shown in previous studies (e.g., Kim & Thompson, 2000; Thompson, 2003; Thompson, Lange, Schneider, & Shapiro, 1997), and suggest a syntactic basis for verb production deficits in agrammatism. Conversely, the semantic complexity of verbs affected PrAD, but not agrammatic, patients' performance, suggesting "bottom-up" breakdown in their verb lexicon, paralleling that of nouns, resulting from the degradation or loss of semantic features of verbs.     

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.     

Spatial and visual learning deficits in Alzheimer's and Parkinson's disease

Experimental paradigms adopted from animal models were used to compare the neuropsychological mechanisms underlying the dementias of Alzheimer's and Parkinson's diseases. Two tasks were selected because characteristic profiles of impairment in nonhuman primates are seen following selective lesions of frontal cortex, temporal cortex, and fornix. The tasks consisted of a spatial and a visual learning problem, each with two components: (1) original learning and (2) reversal of the original learning. The Alzheimer's patients were significantly impaired on original learning and reversal learning in the visual modality compared with demented Parkinson's patients, even though both groups were equated for severity of dementia. On the spatial tasks, both the Alzheimer's and the demented Parkinson's patients were impaired on reversal learning but not on original learning. The profile of deficits on the visual tasks may serve to differentiate Alzheimer's from Parkinson's dementia and may reflect selective orbitofrontal system lesions in the former.     

Development of clinical vignettes to assess healthcare decision-making capacity in elderly with mild cognitive impairment and Alzheimer's disease

IntroductionCognitive impairment can constrict healthcare decision-making capacity, as it affects the ability to understand, appreciate, and reason with information, as well as communication abilities. Therefore, decision-making capacity of elders with mild cognitive impairment or Alzheimer's disease should be carefully assessed when patients are asked to make decisions regarding their health. Vignettes are particularly relevant to assess healthcare decision capacity, since they can come close to real life situations and improve statistical reliability of capacity assessment instruments.ObjectiveThis paper describes the construction and development process of three hypothetical vignettes, to be included in a new Portuguese assessment tool of healthcare decision-making capacity (CAI-Health).MethodFor vignettes’ development, examples from other assessment tools were first reviewed to summarize their text length, language complexity and health information contained. Most prevalent causes of mortality and morbidity in Portuguese elders were then identified, in order to select the health issues to include in CAI-Health’ vignettes. Seven vignettes were developed, and three were selected to be included in CAI-Health. After vignette's selection, these were reviewed by three experienced medical experts, during a focus group.ConclusionVignettes final version include cases of increased complexity, presenting situations of mild cognitive impairment, lung tumor and knee arthrosis.     

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.     

Self-awareness and self-monitoring of cognitive and behavioral deficits in behavioral variant frontotemporal dementia, primary progressive aphasia and probable Alzheimer's disease

Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight. Different components of insight, self-awareness and self-monitoring, are also often considered separate phenomena. The current study compared insight in patients with PPA, bvFTD, and probable Alzheimer's disease (PrAD) and a group of cognitively intact control subjects. Additionally, differences in insight for the domains primarily affected by the three types of dementia, namely, Behavior, Naming, and Memory, were assessed, and self-awareness and self-monitoring were compared. A total of 55 participants were enrolled. Participants were asked to complete self-estimate scales demonstrating their perceived ability immediately prior to, and immediately following a test in each domain of interest. Results indicated that PPA and normal control groups performed very similarly on control (Weight and Eyesight) and cognitive domains, whereas bvFTD and PrAD patients were unable to accurately assess Memory. All three diagnostic groups failed to accurately assess their behavioral symptoms, suggesting that this domain is vulnerable to loss of insight across diagnoses. Naming ability, in contrast, was either accurately assessed or underestimated in all groups. Finally, there were no notable differences between self-awareness and self-monitoring, potential explanations for this are examined.     

Executive deficits appearing in the initial stage of Alzheimer's disease

The presence of executive deficits has been sought at a stage of Alzheimer's disease where currently used neuropsychological batteries could not yet distinguish Alzheimer's patients from normal age- and education-matched controls. This study shows that, at this early stage, those patients that 6 months later are found to show clear signs of Alzheimer's had been significantly worse than normal controls in an executive function task adapted from the Brown-Peterson procedure.     

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.     

Common and specific cognitive deficits in schizophrenia: relationships to function

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.     

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.     

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.     

Ciproxifan, an H3 receptor antagonist, alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer's disease

Previous research has indicated that the blockade of H(3)-type histamine receptors may improve attention and memory in normal rodents. The purpose of this study was to determine if ciproxifan, an H(3) receptor antagonist, could alleviate the hyperactivity and cognitive deficits observed in a transgenic mouse model (APP(Tg2576)) of Alzheimer's disease. APP(Tg2576) mice displayed significantly greater locomotor activity than wild-type mice, but APP(Tg2576) mice provided with daily ciproxifan treatment showed activity levels that did not differ from wild-type mice. In the swim maze, APP(Tg2576) mice exhibited significantly longer escape latencies, but the APP(Tg2576) mice treated daily with ciproxifan had latencies that were indistinguishable from controls. In probe trials conducted one hour after the last training trial, ciproxifan-treated APP(Tg2576) mice spent more time near the previous platform location and made more crossings of this area than did saline-treated APP(Tg2576) mice. APP(Tg2576) mice also demonstrated a significant impairment in the object recognition task that was reversed by acute treatment with ciproxifan (3.0mg/kg). These data support the idea that modulation of H(3) receptors represents a novel and viable therapeutic strategy in the treatment of Alzheimer's disease.     

Patterns of neuropsychological performance in multiple system atrophy compared to sporadic and hereditary olivopontocerebellar atrophy

Although neuropsychological symptoms are associated with multiple system atrophy (MSA), sporadic olivopontocerebellar atrophy (sOPCA), and dominantly inherited olivopontocerebellar atrophy (dOPCA), the differences between these groups have not been explored. We compared 28 MSA patients on psychiatric rating scales and neuropsychological measures to 67 sOPCA patients, 42 dOPCA patients, and 30 normal controls. Patients with dOPCA, sOPCA, and MSA all exhibited significant deficits on motor-related tasks, as well as relatively mild deficits in cognitive functioning. Patients with MSA had greater neuropsychological dysfunction, particularly in memory and other "higher order" cognitive processes, than patients with either sOPCA or dOPCA.