Word association in early Alzheimer's disease

The hypothesis that Alzheimer's disease (AD) degrades semantic representations predicts that AD qualitatively alters spontaneous thoughts. In two experiments contrasting free associations to words with strong (e.g., bride-groom) versus weak (e.g., body-leg) associates participants with AD produced less common responses (e.g., bride-pretty) than normal controls but only for words with strong associations, and only on the first (but not on second or third) association response. Furthermore, all participants produced fewer semantically related responses to words with weak associates. Because strong associations should be retrieved more easily than weak associations these results are problematic for retrieval-based accounts of AD. Instead we propose that AD entails a semantic deficit, and that strong associations involve more semantic processing than weak associations (in all speakers).     

Knowledge of natural kinds in semantic dementia and Alzheimer's disease

We examined the semantic impairment for natural kinds in patients with probable Alzheimer's disease (AD) and semantic dementia (SD) using an inductive reasoning paradigm. To learn about the relationships between natural kind exemplars and how these are distinguished from manufactured artifacts, subjects judged the strength of arguments such as "Humans have a chemical called sebum. Therefore, frogs have a chemical called sebum." These judgments depend on subjects' perception of the similarity between the familiar objects named in the premise and the conclusion. Controls rated arguments generalizing from a natural kind to an artifact as significantly weaker than arguments generalizing from one natural kind to another natural kind. SD patients demonstrated a graded profile of generalization without evidence of a categorical distinction between natural kinds and artifacts. AD patients' judgments also suggested more difficulty than controls at distinguishing between natural kinds and artifacts. Both SD patients and AD patients resembled controls in their judgments of arguments where both objects are from the natural kinds category. Semantic knowledge thus appears to be sufficiently preserved in both AD and SD to support within-category similarity judgments. We suggest that SD patients may be impaired in part at identifying the features critical to diagnosing membership in a semantic category, while AD patients' performance is consistent with their semantic categorization deficit.     

Word recognition in Alzheimer's disease: Effects of semantic degeneration

Impairments of word recognition in Alzheimer's disease (AD) have been less widely investigated than impairments affecting word retrieval and production. In particular, we know little about what makes individual words easier or harder for patients with AD to recognize. We used a lexical selection task in which participants were shown sets of four items, each set consisting of one word and three non‐words. The task was simply to point to the word on each trial. Forty patients with mild‐to‐moderate AD were significantly impaired on this task relative to matched controls who made very few errors. The number of patients with AD able to recognize each word correctly was predicted by the frequency, age of acquisition, and imageability of the words, but not by their length or number of orthographic neighbours. Patient Mini‐Mental State Examination and phonological fluency scores also predicted the number of words recognized. We propose that progressive degradation of central semantic representations in AD differentially affects the ability to recognize low‐imageability, low‐frequency, late‐acquired words, with the same factors affecting word recognition as affecting word retrieval.     

Differential memory impairment in dementia with Lewy bodies and Alzheimer's disease

This study was conducted in order to elucidate the functioning of the Central Executive System of Working Memory (WM) and to clarify the status of other cognitive functions in Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Fourteen DLB, 22 AD, and 23 control subjects were assessed with the dual task paradigm and other cognitive tests. When compared with controls, DLB subjects performed more poorly in concurrent conditions on semantic WM tasks, and AD subjects performed more poorly on the spatial WM task. The DLB subjects had an inferior verbal span and AD subjects, an inferior recall on the CVLT. These data suggest relative impairments of verbal and semantic WM in DLB and relative impairments of spatial WM and verbal episodic memory in AD.     

Strategic value-directed learning and memory in Alzheimer's disease and behavioural-variant frontotemporal dementia

In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants’ memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory.     

Verb agreements during on-line sentence processing in Alzheimer's disease and frontotemporal dementia

An on-line "word detection" paradigm was used to assess the comprehension of thematic and transitive verb agreements during sentence processing in individuals diagnosed with probable Alzheimer's Disease (AD, n=15) and Frontotemporal Dementia (FTD, n=14). AD, FTD, and control participants (n=17) were asked to listen for a word in a sentence. Unbeknownst to the participants, the target word followed an agreement involving a verb's transitivity or thematic role component. Control participants took significantly longer to respond to a target word only when it immediately followed a violation of a thematic role agreement or a transitivity agreement, relative to target word detection immediately following the corresponding correct agreement. AD patients were selectively insensitive to thematic role agreement violations, although they demonstrated a normal processing pattern for transitivity agreements. This is consistent with previous observations showing selective difficulty with the thematic role component of a verb in AD. FTD patients were insensitive to violations of thematic role and transitivity agreements. FTD patients' impairment for both transitivity and thematic role agreements may reflect a broader degradation of verb knowledge that involves both grammatical and semantic representations, or difficulty processing sentence structure that also causes a thematic role deficit.     

Pattern of language impairment is different in Alzheimer's disease and multi-infarct dementia.

Language impairment was assessed in 33 patients with Alzheimer's disease (AD), in 52 patients with multi-infarct dementia (MID), and in 86 elderly community residents. The investigation included the D-Test Battery based on the Luria's Neuropsychological Investigation for all subjects. An extended battery of Luria's language items was used for 30 demented patients (11 AD and 19 MID patients) and 86 controls. The changes in language functions in normal subjects could be clearly differentiated from those seen in patients with mild dementia. The patients with different degrees of dementia differed also significantly from each other in regard to language impairment. Moreover, patients with AD and MID appeared to have different patterns of language impairment although the severity of dementia and the levels of orientation, mnestic, and conceptual functions were equal. AD was associated especially with a defect in understanding of grammatical structures and MID with disorders in recognition of words, naming, and repetition. The differential diagnostic capacity of 23 selected language items proved to be 97% between AD, MID, and control subjects. The results indicate that the examination of language functions is valuable in the differential diagnosis of dementia.     

Divergent thinking in Alzheimer's and frontotemporal dementia

Twenty-three patients with mild dementia of the Alzheimer's type (DAT) or frontotemporal type (DFT) and age- and education-matched control subjects were administered tests of complex fluency involving divergent thinking and tests of letter, category, and figural fluency. The tests of complex fluency discriminated the dementia patients from control subjects more strongly than did the other fluency tests. The results suggest that divergent thinking as assessed by complex fluency tests is a cognitive domain that is impaired early in the course of dementia. The sensitivity of complex fluency tests compared to that of letter, category, and figural fluency tests may be related to greater demands for conceptualization in relating stimulus attributes to function and greater demands for flexible thinking during self-directed search processes.     

Word frequency and list composition effects in associative recognition and recall

The effects of list composition and word frequency on cued recall, associative recognition, and item recognition were examined in three experiments For pure-frequency lists, cued recall and associative recognition show better performance on common high-frequency (HF) words than on rare low-frequency (LF) words. Item recognition, however, shows an advantage for LF words. In mixed lists, consisting of half HF and half LF words, the HF advantage in cued recall disappeared; however, the word frequency effects in item and associative recognition were unchanged. These results are inconsistent with explanations based on differential attention or co-rehearsal of KF and LF words. However, the results are consistent with list strength results which show that recognition is insensitive to strength-based list composition, but that recall is sensitive to list composition.     

Category and letter fluency in semantic dementia, primary progressive aphasia, and Alzheimer's disease

This study examined the impact of various degenerative dementias on access to semantic knowledge and the status of semantic representations. Patients with semantic dementia, primary progressive aphasia, and Alzheimer's disease were compared with elderly controls on tasks of category and letter fluency, with number of words generated, mean lexical frequency and errors recorded. The findings are consistent with the view that category and letter fluency rely on both common and unique cognitive processes. Fluency tasks, with the richness of data obtained, are valuable in distinguishing different dementia syndromes from one another.     

Pattern of intrusions in verbal recall: comparison of Alzheimer's disease, Parkinson's disease, and frontal lobe dementia

Although some researchers have suggested that intrusions in word list learning are more frequent in Alzheimer's disease, recent studies have shown that this might not be true. In fact, intrusions are common in many neurological degenerative diseases. The goal of the present study was to examine the types of intrusions made by three groups of patients, namely patients with Parkinson's disease (PD), Alzheimer's disease (AD), and dementia with prominent frontal lobe semiology (FD). Although PD patients learned more words (trials 1 to 5 on the RAVLT) than the two other groups, there was no significant difference in the total number of intrusions. However, significant differences between groups were observed for nonrelated intrusions, the proportion of PD patients (15.4%) being lower than the proportion of AD (45.5%) and FD (45.8%) patients with this type of intrusions. No other type of intrusions (same category, recurring, phonemic) significantly differentiated between the three groups. The proactive interference effect (PI), measured as the difference between first recall of list A and list B recall, was stronger in PD than in the two other groups, reflecting the strong positive correlation between total number of words recalled on the RAVLT and severity of the PI effect. Prior list intrusions (intrusions from list A while recalling list B items) were significantly more pronounced in FD than in the two other groups. Finally, free associations (series of intrusions related to one another but not to the target items) were observed almost exclusively in FD patients. These findings illustrate some qualitative differences between various neurological degenerative diseases. They also stress the marked similarities between AD and FD with regards to verbal learning.     

Clock drawing performance and brain morphology in mild cognitive impairment and Alzheimer's disease

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimer's disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter (GM) density throughout the entire brain. In the first step of analysis (p<.001, uncorrected), VBM revealed a reduced GM density in numerous cortical (temporal lobe, frontal lobe, parietal lobe, cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be associated with poorer CDT performance. When corrected for multiple comparisons (p<.01), the associations remained significant predominantly in the left temporal and--less pronounced--the right temporal lobe. VBM demonstrated CDT performance to depend on the integrity of widely distributed cortical and subcortical areas in both brain hemispheres with accentuation in the left-sided temporal lobe region.     

Caregiver religiosity and well-being in dealing with Alzheimer's dementia

To examine the relationship among religious participation, stress, and well-being, 84 caregivers of Alzheimer's patients and 81 control subjects completed the Religiosity Scale, Life-3, and Medical Outcomes Study well-being measures. Caregivers only completed the Relative's Stress Scale. No differences were found between groups in religious practices, although caregivers indicated higher levels of clergy-visiting than the others and control subjects indicated a greater met need for contact with the church or synagogue. In contrast, control subjects show higher levels of well-being, social functioning, and mental health than caregivers. In care-givers, significant relationships were found among several religiosity variables, stress, and well-being.     

An experimental approach to detecting dementia in Down syndrome: a paradigm for Alzheimer's disease

Measures developed from animal models of aging may detect dementia of the Alzheimer's type in a population at-risk for Alzheimer's disease (AD). Although, by middle age, individuals with Down syndrome (DS) show an extraordinarily high prevalence of AD-type pathology, their severe idiopathic cognitive deficits tend to confound the clinical diagnosis of AD. The current study was designed to improve detection of AD in DS by using measures of learning and memory derived from animal models of aging. Adults with DS (N=34) were assessed and reassessed (n=19) approximately one year later using stimulus-response (S-R) test methods derived from experimental literature, as well as standardized informant-based tests. Results demonstrated high validity and reliability of select tests. The implication of early symptom detection in a population at-risk for AD-type dementia was discussed in terms of potential brain regions of interest.     

Word List Generation Performancein Alzheimer's Disease and Vascular Dementia

Word list generation (WLG) was examined among clinical samples of individuals with Alzheimer's disease (AD) (n = 73) or ischemic vascular dementia (IVD) (n = 85), equivalent in age, education, current and estimated premorbid intellectual functioning, and proportion of men and women. The AD group performed significantly better than did the IVD group on lexical WLG, and a trend was observed indicating superior performance among the IVD group on categorical WLG. Within-groups, comparisons of group means, and profile analyses of individual performance patterns all indicated that persons with AD demonstrated a lexical > categorical pattern significantly more often than did IVD participants. The absolute difference in average performance between the AD and IVD groups on lexical and categorical WLG was small; the findings, however, generally support the clinical utility of the lexical > categorical WLG pattern in the differential diagnosis of AD and IVD. The patterns of performance support the presence of relative impairment in semantic processing among the individuals with AD and global deficits in retrieval and processing speed in individuals with IVD.     

Frontal lobe dementia and subcortical vascular dementia: a neuropsychological comparison

We compared the performance of 40 patients with frontal lobe dementia to that of 40 patients with subcortical vascular dementia (80 patients including, 46 men and 34 women) in a set of tasks assessing attentional, executive, and behavioural tasks. The frontal lobe dementia represents an important cause for degenerative disruption and is increasingly recognised as an important form (up to 25%) of degenerative dementia among individuals of late-middle-age. The main involvement is the frontal-subcortical pathway, which is the final target of impairment even in subcortical vascular dementia. A wider involvement of the cortical (decisional) layers in frontal dementia, in contrast with the prominent and widespread involvement of the subcortical pathways (refinement and corrections programs) creates the different profiles of the two groups. Frontal patients have more difficulties in abstract reasoning, focusing attention, and implementing strategies to solve problems. They exhibit more profound behavioural alterations in personality and social conduct and show only moderate depression, and a total lack of insight concerning their dinical condition. In contrast, the patients with subcortical vascular dementia have poor general cognitive functions, high insight, and important depression and apathy as the principal and most salient characteristic of their behavioral conduct.