CT scan and neuropsychological correlates of Alzheimer's disease and Huntington's disease

"Cortical" and "subcortical" dementia syndromes differ in areas of primary neuropathology and clinical characteristics. Conventional CT scan interpretation, visual inspection of pictures, has not been useful in studying dementia. Recent studies of the digitally stored CT attenuation values have found systematic variations with normal aging and aphasia subtypes. In this study of numerical CT scan information in four Alzheimer's Disease and two Huntington's Disease patients, a double dissociation of frontal and temporal lobe density values was found, and a significant correlation was found between left temporal lobe density and verbal ability measures in the Alzheimer's Disease patients.     

The impact of left and right intracranial tumors on picture and word recognition memory

This study investigated the effects of left and right intracranial tumors on picture and word recognition memory. We hypothesized that left hemispheric (LH) patients would exhibit greater word recognition memory impairment than right hemispheric (RH) patients, with no significant hemispheric group picture recognition memory differences. The LH patient group obtained a significantly slower mean picture recognition reaction time than the RH group. The LH group had a higher proportion of tumors extending into the temporal lobes, possibly accounting for their greater pictorial processing impairments. Dual coding and enhanced visual imagery may have contributed to the patient groups' similar performance on the remainder of the measures.     

Mimicking aphasic semantic errors in normal speech production: evidence from a novel experimental paradigm

Semantic errors are commonly found in semantic dementia (SD) and some forms of stroke aphasia and provide insights into semantic processing and speech production. Low error rates are found in standard picture naming tasks in normal controls. In order to increase error rates and thus provide an experimental model of aphasic performance, this study utilised a novel method- tempo picture naming. Experiment 1 showed that, compared to standard deadline naming tasks, participants made more errors on the tempo picture naming tasks. Further, RTs were longer and more errors were produced to living items than non-living items a pattern seen in both semantic dementia and semantically-impaired stroke aphasic patients. Experiment 2 showed that providing the initial phoneme as a cue enhanced performance whereas providing an incorrect phonemic cue further reduced performance. These results support the contention that the tempo picture naming paradigm reduces the time allowed for controlled semantic processing causing increased error rates. This experimental procedure would, therefore, appear to mimic the performance of aphasic patients with multi-modal semantic impairment that results from poor semantic control rather than the degradation of semantic representations observed in semantic dementia [Jefferies, E. A., & Lambon Ralph, M. A. (2006). Semantic impairment in stoke aphasia vs. semantic dementia: A case-series comparison. Brain, 129, 2132-2147]. Further implications for theories of semantic cognition and models of speech processing are discussed.     

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.     

Clinical and non-clinical hallucinations are similarly associated with source memory errors in a visual memory task

Hallucinations have been found to be associated with various types of source memory failure in both schizophrenia patients and hallucination-prone healthy individuals. We investigated the associations of clinical and non-clinical hallucinations with source memory errors in a visual memory task that involved the remembering of picture presentation context. 59 schizophrenia patients and 61 healthy individuals took part in the study. Pictures were presented either at different locations or in association with different visual stimuli. The participants were required afterwards to recognize the target pictures among distractors, and then to remember their spatial location or the visual stimulus that was associated with them. Liberal response bias in picture recognition was associated with hallucination proneness and auditory-verbal hallucinations in subsamples of participants with significant non-clinical or clinical hallucinations. After controlling for overall memory performance, failure to remember the spatial location of the pictures was associated with visual hallucinations in male patients; failure to remember the associated visual stimulus was related to auditory-verbal hallucinations in female patients and to hallucination proneness in healthy women. The findings suggest that both clinical and non-clinical hallucinations are associated with loss of contextual information relative to the acquisition of events.     

Pragmatics of measuring recognition memory: applications to dementia and amnesia

This article has two purposes. The first is to describe four theoretical models of yes-no recognition memory and present their associated measures of discrimination and response bias. These models are then applied to a set of data from normal subjects to determine which pairs of discrimination and bias indices show independence between discrimination and bias. The following models demonstrated independence: a two-high-threshold model, a signal detection model with normal distributions using d' and C (rather than beta), and a signal detection model with logistic distributions and a bias measure analogous to C. C is defined as the distance of criterion from the intersection of the two underlying distributions. The second purpose is to use the indices from the acceptable models to characterize recognition memory deficits in dementia and amnesia. Young normal subjects, Alzheimer's disease patients, and parkinsonian dementia patients were tested with picture recognition tasks with repeated study-test trials. Huntington's disease patients, mixed etiology amnesics, and age-matched normals were tested by Butters, Wolfe, Martone, Granholm, and Cermak (1985) using the same paradigm with word stimuli. Demented and amnesic patients produced distinctly different patterns of abnormal memory performance. Both groups of demented patients showed poor discrimination and abnormally liberal response bias for words (Huntington's disease) and pictures (Alzheimer's disease and parkinsonian dementia), whereas the amnesic patients showed the worst discrimination but normal response bias for words. Although both signal detection theory and two-high-threshold discrimination parameters showed identical results, the bias measure from the two-high-threshold model was more sensitive to change than the bias measure (C) from signal detection theory. Three major points are emphasized. First, any index of recognition memory performance assumes an underlying model. Second, even acceptable models can lead to different conclusions about patterns of learning and forgetting. Third, efforts to characterize and ameliorate abnormal memory should address both discrimination and bias deficits.     

Very Early Decline in Recognition Memory for Odors in Alzheimer’s Disease

When in the progression of Alzheimer’s disease (AD) a decline in detection sensitivity and recognition memory for odors begins, and whether a fast progression in dementia is related to a fast loss in odor sensitivity, was determined by studying 78 patients with probable AD, categorized as very mild, mild, or moderate in degree of dementia, and 78 controls. Taste and vision were studied for comparison. Whereas the earliest decline in odor sensitivity and visual memory was found in mild patients, a decline in odor memory was found in the very mild patients. Similar taste thresholds in the four groups suggest that the poor odor detectability in AD was not related to task demands in threshold testing. A fast progression in dementia was also found to be related to a fast loss in odor sensitivity. The findings imply that memory-based olfactory tests may contribute to early diagnosis of AD.     

Task Demands and Sentence Comprehension in Patients with Dementia of the Alzheimer's Type

Patients with dementia of the Alzheimer's type (DAT) and matched normal controls were given three tests of syntactic comprehension in which nonlinguistic visual and memory task demands were varied. In all tasks, subjects were presented spoken semantically reversible sentences with a variety of syntactic structures and required to match the sentence to a picture. In the first experiment, subjects matched the spoken sentence to one of two pictures that appeared either before or immediately following the presentation of the sentence. The target picture depicted the spoken sentence correctly and the foil depicted the reversed thematic roles to those in the sentence (i.e., it was a syntactic foil). The second experiment employed a sentence video-verification task in which subjects were required to determine if the spoken sentence matched a videotaped depiction of the action in the sentence or a syntactic foil. In the third experiment, in different conditions, subjects were required to determine whether the spoken sentence matched a single picture or to choose the picture that matched the sentence from an array of two or three pictures. In this experiment, both lexical and syntactic foils were used. In all tasks, DAT patients were affected by the number of propositions in the presented sentence, but not by the syntactic complexity of the sentence. Control subjects also were unaffected by the syntactic complexity of the sentence; the number-of-proposition effect was present in some experiments in the control population. Comparison of performance across the one-, two-, and three-picture versions of the task showed that the magnitude of the effect of number of propositions increased as the number of pictures in the array increased. In addition, analysis of the data from each of the tasks separately showed that the effect of number of propositions only occurred when subjects were attempting to match the target to a syntactic foil (one-picture version) or to choose between the target and a syntactic foil (two- and three-picture versions). The results support the view that patients with DAT do not have disturbances affecting syntactic processing. In addition, they suggest that the effect of number of propositions arises at a stage of analysis that is partially separate from assigning sentence meaning, such as in holding a representation of the sentence in memory until the pictures can be analyzed and encoded and/or in comparing the results of the picture analysis with a stored representation of the sentence meaning.     

Object alternation and orbitofrontal system dysfunction in Alzheimer's and Parkinson's disease

Previous performance on measures of frontal system function have suggested prominent orbitofrontal system damage in Alzheimer's disease, but not in Parkinson's dementia. Object alternation (OA), a task sensitive to orbitofrontal system dysfunction in non-human animals, was therefore administered to determine whether this measure would distinguish Alzheimer's from Parkinson's dementia. OA was significantly impaired in Alzheimer's disease compared to Parkinson's dementia, even though both groups were equated for severity of dementia. Although the patients with Parkinson's dementia also showed impairment on OA compared to normals, an error analysis revealed that the performance of the Alzheimer's patients, but not the Parkinson's patients, was characterized by abnormal response perseveration. The marked perseverative deficit in Alzheimer's disease may reflect orbitofrontal system dysfunction whereas the milder, and qualitatively different, deficits in Parkinson's disease may reflect dorsolateral frontal system involvement.     

Implications of memory and language dysfunction in the naming deficit of senile dementia

Young normals, elderly normals, and patients with either mild-to-moderate or severe senile dementia of the Alzheimer type (SDAT) were administered several tests of language function and remote memory. On all of the language tests examined, elderly normals exhibited a mild, nonsignificant performance decrement relative to the young normals. Advanced SDAT patients were markedly impaired on all of the tests. Early dementia patients were most impaired, relative to aged normals, on tests of object naming, category instance fluency, and remote memory. The deficit was smaller on the WAIS vocabulary subtest, on selecting the name of a visually presented object, and on recalling the function of an object. Early SDAT patients were least impaired in selecting the picture of an object after its name had been provided and in selecting objects that belong to a specified functional category. The results are consistent with the notion that the language dysfunction in early SDAT is due to a deficit in semantic memory function in which general, categorical information remains available whereas information about specific attributes becomes less accessible. The object naming test might be useful in the assessment of treatment effects upon SDAT because of its sensitivity and specificity to dementia, its high face validity, and its independence of recent memory.     

A visual object stimulus database with standardized similarity information

Although many visual stimulus databases exist, none has data on item similarity levels for multiple items of each kind of stimulus. We present such data for 50 sets of grayscale object photographs. Similarity measures between pictures in each set (e.g., 25 different buttons) were collected using a similarity-sorting method (Goldstone, Behavior Research Methods Instruments & Computers, 26(4):381–386, 1994). A validation experiment used data from 1 picture set and compared responses from standard pairwise measures. This showed close agreement. The similarity-sorting measures were then standardized across picture sets, using pairwise ratings. Finally, the standardized similarity distances were validated in a recognition memory experiment; false alarms increased when targets and foils were more similar. These data will facilitate memory and perception research that needs to make comparisons between stimuli with a range of known target–foil similarities.     

The semantic category effect increases with worsening anomia in Alzheimer's type dementia

A large number of patients (n=72) with probable Alzheimer's type dementia (DAT) and mild cognitive impairment (MCI) carried out a picture naming task which comprised stimuli from biological and nonbiological categories. The results were stratified into five ranges of overall naming ability. Every group except those with scores within the range of elderly normal individuals demonstrated better nonbiological naming than biological naming, an effect which increased with worsening impairment. In general, patients diagnosed with other dementia (n=15) did not fit well within the pattern of the DAT/MCI participants, except those known to have a significant semantic impairment. A category effect favoring nonbiological items appears to be robust and produce a predictable pattern across progressive levels of impairment in AD.     

Lärmendes Verhalten und störende Lautäußerungen bei Patienten mit Demenz

Loud behavior and disruptive vocalizations occur relatively frequently in patients with dementia together with agitation and other behavioral problems. An unambiguous diagnosis is important to take targeted therapeutic measures. First, nonpharmacological measures should be tried and the triggering stressors should be identified and eliminated if possible. Guidelines for the treatment of behavioral disorders, thus also for loud behavior, recommend behavioral therapy, cognitive–emotional training, sensory stimulation therapy, and psychosocial interventions. Targeted therapeutic measures can provide relief for the person with dementia and the relatives and nurses.     

Neuropsychological Measures that Predict Progression from Mild Cognitive Impairment to Alzheimer's type dementia in Older Adults: a Systematic Review and Meta-Analysis

This study aimed to determine the extent to which cognitive measures can predict progression from mild cognitive impairment (MCI) to Alzheimer’s type dementia (AD), assess the predictive accuracy of different cognitive domain categories, and determine whether accuracy varies as a function of age and length of follow-up. We systematically reviewed and meta-analyzed data from longitudinal studies reporting sensitivity and specificity values for neuropsychological tests to identify individuals with MCI who will develop AD. We searched articles in Medline, Cochrane, EMBASE, PsycINFO, and the Web of Science. Methodological quality was assessed using the STARDem and QUADAS standards. Twenty-eight studies met the eligibility criteria (2365 participants) and reported predictive values from 61 neuropsychological tests with a 31-month mean follow-up. Values were pooled to provide combined accuracy for 14 cognitive domains. Many domains showed very good predictive accuracy with high sensitivity and specificity values (≥ 0.7). Verbal memory measures and many language tests yielded very high predictive accuracy. Other domains (e.g., executive functions, visual memory) showed better specificity than sensitivity. Predictive accuracy was highest when combining memory measures with a small set of other domains or when relying on broad cognitive batteries. Cognitive tests are excellent at predicting MCI individuals who will progress to dementia and should be a critical component of any toolkit intended to identify AD at the pre-dementia stage. Some tasks are remarkable as early indicators, whereas others might be used to suggest imminent progression.     

Apolipoprotein epsilon4 is associated with more rapid decline in odor identification than in odor threshold or Dementia Rating Scale scores

Individuals with the apolipoprotein E epsilon4 genetic risk factor for Alzheimer's disease (AD) show deficits in olfactory function. The purpose of the present study was to examine longitudinally odor identification (odor ID), odor threshold, picture identification, and global cognitive status in allele positive (epsilon4+) and negative (epsilon4-) persons. Participants were initially given the San Diego Odor Identification test, an odor threshold test, and the Dementia Rating Scale (DRS). Participants were re-tested approximately four years later. The results indicate: (1) odor ID declined more rapidly in epsilon4+ than in epsilon4- normal elderly adults; (2) neither group exhibited a significant decline in odor threshold, picture identification or DRS scores. These results suggest that declines in odor identification occur before declines in other measures of dementia in persons at risk for AD because of their APOE allele genetic status.     

Nuisance parameters in the assessment of noncognitive manifestations of dementia.

Measures of noncognitive disturbances in dementia typically rely on ratings by informants. In this study, method variance in measures of affect, behavior, and functional competence was evaluated by comparing ratings from 2 types of informants (spouse vs. child) in patients with probable Alzheimer's disease. No differences were observed on 5 variables; for 2 measures of behavior disturbance and 1 measure of functional disability, ratings obtained from child informants were significantly higher than spouse ratings for patients at comparable levels of dementia severity. Although the effect of the rater dimension was relatively small and selective, the findings suggest the need for further research on potential sources of bias in the ratings of noncognitive features of the dementia syndrome.     

Famous people knowledge and the right and left temporal lobes

It is generally accepted that the anterior temporal lobes support knowledge of famous people. The specific roles of the right and left temporal lobe remain a subject of debate, with some studies suggesting differential roles based on modality (visual versus verbal information) and others category (person knowledge versus general semantics). The present study re-examined performance of semantic dementia patients with predominantly right and predominantly left temporal lobe atrophy on famous face, famous name and general semantic tasks, with the specific aim of testing the hypothesis that the right temporal lobe has a privileged role for person knowledge and the left temporal lobe for general semantic knowledge. Comparisons of performance rankings across tasks showed no evidence to support this hypothesis. By contrast, there was robust evidence from naming, identification and familiarity measures for modality effects: right-sided atrophy being associated with relatively greater impairment for faces and visual tasks and left-sided atrophy for names and verbal tasks. A double dissociation in test scores in two patients reinforced these findings. The data present a challenge for the influential `semantic hub' model, which views the anterior temporal lobes as an area of convergence in which semantic information is represented in amodal form.     

Cognitive Testing Battery: differences among groups with dementia, Huntington's disease, and controls

This study evaluated a new test for dementia, the Cognitive Testing Battery, used for over six years in outpatient clinics for aging-related disorders. This battery was developed to be brief, easy to administer, and to provide useful feedback as a cognitive profile for clinicians, patients, and caregivers. 489 participants were tested during a 5-yr. period. Multidisicplinary teams diagnosed these patients with dementia, depression, or Huntington's Disease. A control group was also included. Groups were then compared on the 10 key subscales that subserve dementia populations. Analysis showed there were significant differences among the groups on all measures and that selected scales differentiated the groups. The total score maximally differentiated the groups, and the dementia group was most different from the other groups.