Biomedical subjects

D P Salmon

Publications and source records attributed to D P Salmon.

At least 19 recordsLinked to original sources

PubMed2005

Rate of progression differs in frontotemporal dementia and Alzheimer disease.

OBJECTIVE: To compare survival and rates of cognitive and functional decline in patients with autopsy-confirmed frontotemporal dementia (FTD) and Alzheimer disease (AD) in a large multicenter study. BACKGROUND: Despite advances in the clinical characterization of FTD, little is known about its rate of progression. Characterizing survival and rate of decline in FTD is important because it can provide prognostic guidelines and benchmarks to use in the evaluation of disease-modifying drugs. METHODS: Seventy patients with FTD and 70 patients with AD who were followed by seven Alzheimer disease research centers until confirmation of diagnosis at autopsy were matched for overall age, education, and Mini-Mental State Examination (MMSE) score at initial evaluation. Survival and rates of cognitive and functional decline were compared. RESULTS: Patients with FTD had significantly shorter survival from initial evaluation to death than patients with AD (FTD = 4.2 years, AD = 6.0 years; log-rank test = 5.17, p < 0.05), and they declined significantly faster over one year on the MMSE (mean annual rate of change: -6.7 points for FTD vs -2.3 points for AD). A significantly greater proportion of patients with FTD were impaired in basic activities of daily living (ADLs) at initial evaluation, and lost the capacity for independent or minimally-assisted ADLs over the subsequent year. CONCLUSIONS: The results are consistent with shorter survival and faster rates of cognitive and functional decline in patients with frontotemporal dementia (FTD) compared to those with Alzheimer disease (AD). This suggests that FTD follows a more malignant disease course than AD once dementia is clinically recognized.

Activities of Daily Living↗

PubMed2004

In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Adult↗

PubMed2004

Alzheimer disease without neocortical neurofibrillary tangles: "a second look".

OBJECTIVE: To compare the clinical and pathologic features of plaque only Alzheimer disease (POAD) with plaque and tangle Alzheimer disease (PTAD). METHODS: An autopsy series of 16 patients with POAD and 32 subjects with PTAD on whom extensive antemortem neuropsychological testing was available. Plaques, tangles, and cerebral amyloid angiopathy were examined in the neocortex and hippocampus using thioflavin S staining. In addition, immunocytochemical analysis with AT8 for phosphorylated tau was performed. Midfrontal (MF) synaptic density, MF choline acetyltransferase (ChAT) activity, and apolipoprotein E genotyping were also assessed. RESULTS: Initial neuropsychological test scores and rates of cognitive decline on the Mini-Mental State Examination and Blessed Information-Memory-Concentration were similar between the two groups. However, compared to PTAD, POAD patients tended to deteriorate more slowly on the Mattis Dementia Rating Scale. Furthermore, they were somewhat less impaired on all these measures at last examination. There was an older age at onset and death, and a trend toward a shorter disease duration, in POAD compared to PTAD patients. POAD subjects, by definition, had no neocortical neurofibrillary tangles (NFT) (Braak stages IV or less). In addition, they also had fewer hippocampal NFT, fewer neuritic plaques, and higher mean MF ChAT activity than PTAD subjects. On the other hand, the two groups did not differ significantly in brain weight or MF synaptic density. Although lacking overt tangle formation, the POAD group displayed abnormal phosphorylated tau immunoreactivity in neocortical pyramidal neurons. CONCLUSIONS: Dementing syndromes virtually indistinguishable from each other can, and do, develop in the presence or absence of neocortical NFT. Patients without neocortical NFT are, on average, older at disease onset and death, and show a trend toward a shorter disease duration with somewhat slower deterioration. Although neocortical NFT per se are not obligatory for the development of clinical dementia, more subtle neocortical cytoskeletal tau pathology may contribute to cognitive decline in these subjects.

Aged↗

PubMed2003

Neuromotor abnormalities and risk for psychosis in Alzheimer's disease.

BACKGROUND: Cross-sectional studies in Alzheimer's disease (AD) show a strong relationship between extrapyramidal motor signs and presence of psychosis, yet it remains unclear whether neuromotor abnormalities precede and therefore can predict development of psychosis in AD. OBJECTIVE: To identify cognitive and motor risk factors for the development of psychosis in patients with AD. METHODS: Baseline clinical motor ratings and instrumental measures of neuromuscular function were obtained from 54 nonpsychotic patients with AD who were evaluated annually for 2 years for the development of psychosis. Survival analyses were performed to identify incidence and risks associated with psychosis. RESULTS: The incidence of new onset psychosis in our sample was 32.5% in 2 years. Patients with abnormal agonist muscle burst amplitudes during rapid alternating movements of the hand were more likely to develop psychosis than those without (OR = 4.31; p = 0.007). Women with AD also had a higher risk of developing psychosis within 2 years than men (OR = 1.33; p = 0.01). CONCLUSIONS: Using simple noninvasive instrumental procedures for assessing neuromotor function, it may be possible to identify an individual's level of risk for developing psychosis during the course of AD.

Aged↗

PubMed2003

Behavioural abnormalities contribute to functional decline in Huntington's disease.

The independent and relative contributions of motor, cognitive, and behavioural deficits to functional decline in patients with Huntington's disease are examined. Twenty two patients with Huntington's disease were assessed with rating scales for motor dysfunction, cognitive measures of executive functions, and behavioural measures of apathy, executive dysfunction, and disinhibition. Their functional status was assessed with informant based and clinician based ratings of activities of daily living (ADL). A composite apathy/executive dysfunction behavioural index was strongly related to decline in ADL independently and after controlling for motor and cognitive deficits. These results suggest that behavioural dysfunction contributes to functional decline in patients with Huntington's disease and may impede their ability to utilise motor or cognitive skills that remain available in the early stages of the disease.

Activities of Daily Living↗

PubMed2002

Alzheimer's disease can be accurately diagnosed in very mildly impaired individuals.

BACKGROUND: The growing propensity to diagnose AD in individuals with very mild cognitive impairment increases the danger of false-positive diagnostic errors. Unfortunately, there is little systematically acquired information about the accuracy of the AD diagnosis in very mildly impaired patients. OBJECTIVE: To determine the accuracy of the diagnosis of AD in very mildly impaired patients and to identify objective measures that effectively distinguish these patients from elderly normal controls (NC). METHODS: Consecutive patients with Mini-Mental State Examination scores of > or = 24 who received a clinical diagnosis of AD were evaluated annually for at least 3 years. The initial diagnosis was verified or refuted by autopsy or by information obtained in subsequent evaluations. Initial neuropsychological test scores of verified AD patients were compared with those of NC subjects to identify effective diagnostic measures. RESULTS: The diagnosis of AD was confirmed in 98 of 110 (89%) very mildly impaired patients (33/36 by autopsy, 65/74 by disease progression). The diagnosis was inaccurate in 12 patients (11%): Seven were subsequently diagnosed with other neurologic disorders, and five were ultimately found to be normal. Neuropsychological measures of delayed recall, verbal fluency, and global cognitive status (i.e., Mattis Dementia Rating Scale) provided excellent sensitivity (> or = 96%) and specificity (> or = 93%) for differentiating between very mildly impaired AD patients and NC subjects. CONCLUSIONS: When comprehensive assessment procedures are employed, AD can be diagnosed with reasonably high accuracy in very mildly impaired individuals. However, the dementia evaluation should be repeated after approximately 1 year to ensure the accuracy of the initial diagnosis.

Aged↗

PubMed2002

Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD.

BACKGROUND: Frontotemporal dementia (FTD) is currently distinguished from AD primarily on the basis of behavioral features because studies of cognition have shown negligible or inconsistent differences. However, the poor discriminability of cognitive measures may relate to reliance on imprecise clinically diagnosed groups. Therefore, a retrospective examination of neuropsychological test performance in autopsy-confirmed patients is warranted. OBJECTIVE: To compare the pattern of cognitive deficits exhibited by patients with autopsy-confirmed FTD and AD. METHODS: The profiles of cognitive deficits exhibited by patients with neuropathologic diagnosis of FTD (n = 14) or AD (n = 28) were compared. The Mattis Dementia Rating Scale (MDRS), letter and category fluency tests, Wechsler Intelligence Scale for Children-Revised block design test, Boston naming test, and clock drawing test were administered. RESULTS: Multivariate analysis of covariance controlling for age, education, and level of dementia revealed that patients with FTD performed significantly worse than patients with AD on letter and category fluency tests but significantly better on the MDRS memory subscale, block design test, and clock drawing test. A logistic regression model, validated in an independent clinical sample, used letter fluency, MDRS memory, and block design scores to correctly classify 91% of AD patients and 77% of FTD patients. CONCLUSIONS: A double dissociation in the pattern of cognitive deficits exhibited by FTD and AD patients was demonstrated. The FTD patients were more impaired than AD patients on word generation tasks (i.e., verbal fluency) that are sensitive to frontal lobe dysfunction but less impaired on tests of memory and visuospatial abilities sensitive to dysfunction of medial temporal and parietal association cortices.

Aged↗

PubMed2002

Clinical features and changing patterns of neurodegenerative disorders on Guam, 1997-2000.

BACKGROUND: In the 1950s, high-incidence ALS and Parkinson-dementia complex (PDC) were identified among Chamorros, the native inhabitants of Guam. Brains of patients with these syndromes showed widespread neurofibrillary tangles. Although ALS and PDC were reported to have dramatically declined in the 1980s, new cases are still encountered. Late-life dementia has received little study among Chamorros. METHODS: From 1997 to 2000, the authors evaluated newly referred and previously identified patients. They screened first-degree relatives of previous registries, and subjects aged 60 or older. Subjects who scored below a cognitive test cutoff or had symptoms or signs consistent with parkinsonism or ALS underwent psychometric testing, assessment by a neurologist, and laboratory studies as appropriate. Consensus diagnoses were made. RESULTS: The authors identified 194 Chamorros with ALS (n = 10), PD (n = 11), PDC (n = 90), or late-life dementia (n = 83). Mean ages at onset were 55 for ALS, 68 for PDC, 63 for PD, and 74 for dementia. Late-life dementia was more common in women, and met criteria for probable or possible AD. The APOE-epsilon 4 allele frequency was uniformly low regardless of neurologic diagnosis. CONCLUSIONS: The rapid decline of high-incidence ALS on Guam over the past 40 years suggests the contribution of a modifiable environmental factor. PDC remains relatively common, with an unchanged clinical picture apart from later age at onset. Dementia among elderly Chamorros (termed "Mariana dementia") resembles AD. Autopsy studies will clarify whether this dementia is related to AD pathology or represents a late-life neurofibrillary tangle syndrome more closely allied to PDC.

Age of Onset↗

PubMed2002

Abnormal verbal event related potentials in mild cognitive impairment and incipient Alzheimer's disease.

BACKGROUND: It has been reported that patients with amnesia have a reduced effect of word repetition upon the late positive component of the event related potential (ERP), which peaks at around 600 ms after word onset. OBJECTIVE: To study a word repetition ERP paradigm in subjects with mild cognitive impairment. SUBJECTS: 14 patients with mild cognitive impairment (mean mini-mental state examination score = 27); 14 normal elderly controls. METHODS: Auditory category statements were each followed by a single visual target word (50% "congruous" category exemplars, 50% "incongruous") while ERPs were recorded. N400 (an ERP component elicited by semantically "incongruous" words) and LPC amplitude data were submitted to analysis of variance. RESULTS: The latency of the N400 was slower in mild cognitive impairment. In normal controls, the ERPs to "congruous" targets showed a late positive component to new words, which was greatly diminished with repetition. This repetition effect in normal subjects started before 300 ms at right frontal sites, and peaked at approximately 600 ms post-stimulus over posterior sites. In contrast, the group with mild cognitive impairment had a reduced repetition effect (p < 0.02), which started around 500 ms, with a more central distribution. Further comparisons within the cognitive impairment group showed no appreciable congruous word repetition effect among seven individuals who subsequently converted to probable Alzheimer's disease. The congruous word repetition effect in the group with mild cognitive impairment was almost entirely accounted for by the non-converters. The amplitude of the congruous late positive component word repetition effect was significantly correlated (0.38 < or = r < or = 0.73) with several verbal memory measures. CONCLUSIONS: The congruous word repetition ERP effect appears sensitive to the memory impairment in mild cognitive impairment and could have value in predicting incipient Alzheimer's disease.

Aged↗

PubMed2001

Abnormal semantic network for "animals" but not "tools" in patients with Alzheimer's disease.

The effects of Alzheimer's disease (AD) on the organization of semantic knowledge (i.e., the semantic network) for living (e.g., animals) and non-living (e.g., tools) categories was examined. Multidimensional scaling and Pathfinder analyses of data from triadic comparison tasks showed that the semantic network for "animals", but not the network for "tools", was abnormal in patients with AD. Specifically, patients with AD tended to use a different primary dimension than control subjects for categorizing animals and their network was characterized by atypical associations between concepts. The differences in the integrity of the AD patients' networks for "animals" and "tools" was not likely to be an artifact of differences in the difficulty in identifying the stimuli in the two categories as all stimuli were identified on simple naming or matching tasks. These findings support the results of previous studies that have shown the presence of category-specific semantic deficits in patients with AD.

Aged↗

PubMed2001

Cognitive screening and neuropsychological assessment in early Alzheimer's disease.

Cognitive screening and detailed neuropsychological assessment provide a reliable means of detecting dementia in its earliest stages, tracking the progression of cognitive decline over time, and aiding in the differential diagnosis of various dementing disorders. In addition, recent studies have shown that mild cognitive changes, and particularly declines in memory function, are evident in the "preclinical" phase of Alzheimer's disease and may help to identify elderly individuals who are likely to develop dementia in the near future. Until effective and easily obtainable biological markers for detecting the onset and progression of Alzheimer's disease are developed, neuropsychological assessment will continue to have an important role in the dementia evaluation.

Aged↗

PubMed2001

The effects of age, education, and gender on the Mattis Dementia Rating Scale performance of elderly Chinese and American individuals.

A Chinese version of the Mattis Dementia Rating Scale (DRS) was administered to elderly individuals in Hong Kong (n = 104), and their performance on the test was compared with that of elderly participants in San Diego (n = 150). Age and education, but not gender, were significantly related to DRS performance in both groups. The effect of education was greater in the Hong Kong than in the San Diego participants, but this difference was eliminated when individuals with no formal education were removed from the Hong Kong group. Age- and education-matched groups of Hong Kong and San Diego elderly individuals differed in the pattern of DRS subtest performance they produced, even when they did not differ in total DRS score. The Hong Kong participants scored significantly higher than the San Diego participants on the Construction subscale, whereas the opposite pattern was observed on the Initiation/Perseveration and Memory subscales. These results suggest that some DRS subscales or individual subscale items may be susceptible to cultural differences between elderly Chinese and American individuals.

Age Factors↗

PubMed2000

Incidence of and risk factors for hallucinations and delusions in patients with probable AD.

OBJECTIVE: To examine the incidence of and risk factors for hallucinations and delusions associated with patients clinically diagnosed with probable AD. BACKGROUND: Estimates of the incidence of psychosis in AD range widely from 10% to 75%. The risk factors for psychosis of AD are not known, although multiple studies indicate that AD patients with psychosis demonstrate greater cognitive and functional impairment. METHODS: The authors conducted psychiatric evaluations of 329 patients with probable AD from the University of California at San Diego Alzheimer's Disease Research Center to determine the incidence of hallucinations and delusions. They examined data from annual clinical and neuropsychological evaluations to determine whether there were specific risk factors for the development of hallucinations and delusions. RESULTS: Using Cox survival analyses, the cumulative incidence of hallucinations and delusions was 20.1% at 1 year, 36.1% at 2, 49.5% at 3, and 51.3% at 4 years. Parkinsonian gait, bradyphrenia, exaggerated general cognitive decline, and exaggerated semantic memory decline were significant predictors. Age, education, and gender were not significant predictors. CONCLUSIONS: The authors found a relatively high incidence of hallucinations and delusions in patients diagnosed with probable AD and suggest that specific neurologic signs, cognitive abilities, and accelerated decline may be predictive markers for their occurrence.

Alzheimer Disease↗

PubMed2000

Comparison of the serial position effect in very mild Alzheimer's disease, mild Alzheimer's disease, and amnesia associated with electroconvulsive therapy.

Individuals given a series of words to memorize normally show better immediate recall for items from the beginning and end of the list than for mid-list items. This phenomenon, known as the serial position effect, is thought to reflect the concurrent contributions of secondary and primary memory, respectively, to recall performance. The present study compared the serial position effects produced on Trial 1 of the California Verbal Learning Test (CVLT) in mildly demented (N = 25; M MMSE = 20.0) and very mildly demented (N = 25; M MMSE = 25.5) patients with Alzheimer's disease (AD), and age- and education-matched normal control (NC) participants (N = 50). In addition, the serial position effects of the very mildly demented AD patients were compared to those of patients with a transient, circumscribed amnesia arising from a prescribed series of electroconvulsive therapy (ECT) treatments for the relief of depressive illness (N = 11). While the NC group exhibited the typical serial position effect, AD patients recalled significantly fewer words than NC participants overall, and exhibited a significantly reduced primacy effect (i.e., recall of the first 2 list items) with a normal recency effect (i.e., recall of the last 2 list items). Patients with circumscribed amnesia due to ECT were as impaired as the very mildly demented AD patients on most standard CVLT measures of learning and memory, but exhibited primacy and recency effects, which were within normal limits. These results suggest that a reduction in the primacy effect, but not the recency effect, is an early and ubiquitous feature of the memory impairment of AD. It is not, however, a necessary feature of all causes of memory impairment.

Adult↗

PubMed2000

Neurobehaviors and psychotic symptoms in Alzheimer's disease.

Psychotic symptoms are common in Alzheimer's disease (AD) and clinicoanatomical and neuropsychological evidence indicate an association between these symptoms and frontal lobe dysfunction. Neuro-behaviors associated with frontal dysfunction were assessed in Alzheimer's disease (AD) patients with (n = 20) and without psychotic symptoms (n = 21) matched for mean age, education, gender, and dementia severity. The Frontal Lobe Personality Scale (FLOPs) was completed by patient caregivers to measure behaviors typically associated with frontal dysfunction. Findings indicated that AD patients with psychotic symptoms exhibited significantly greater neurobehavioral dysfunction (FLOPs M = 130.69, SD = 24.70) than AD patients without psychotic symptoms (FLOPs M = 111.10, SD = 25.83). Subscale analyses indicated that psychotic AD patients were more dis-inhibited (M = 28.28, SD = 7.54) than patients without psychotic symptoms (M = 20.92, SD = 4.9). Findings are consistent with and contribute to previous neuropsychological and clinicoanatomical research suggesting increased frontal dysfunction in AD with psychotic symptoms and lend additional empirical support to subtyping AD based on the presence of psychotic symptoms. Furthermore, findings provide preliminary evidence indicating which specific type of neurobehavioral abnormalities are related to the presence of distressing psychotic symptoms.

Aged↗

PubMed2000

Word repetition in amnesia. Electrophysiological measures of impaired and spared memory.

Amnesic patients often show improved performance when stimuli are repeated, even in the absence of conscious memory for those stimuli. Although these performance changes are typically attributed to perceptual or motor systems, in some cases they may be related to basic language processing. We examined two neurophysiological measures that vary with word repetition in 12 amnesic patients and 12 control subjects: (i) a late positive component of the event-related potential (ERP) linked to conscious memory and (ii) the N400 component that varies with language comprehension. In each trial, the subject heard a category name, then viewed a word, and then decided whether the word was semantically congruous or incongruous (e.g. 'yes' for 'baby animal: cub'; 'no' for 'water sport: kitchen'). Recall and recognition testing at the end of the experiment showed that control subjects had better memory for congruous than for incongruous words, as did the amnesic patients, who performed less well overall. In contrast, amnesic patients were unimpaired on the category decisions required in each trial and, like the control subjects, showed a large N400 for incongruous relative to congruous words. Similarly, when incongruous trials were repeated after 0-13 intervening trials, N400s were reduced in both groups. When congruous trials were repeated, a late positive repetition effect was observed, but only in the control group. Furthermore, the amplitude of the late positive repetition effect was highly correlated with later word recall in both patients and controls. In the patients, the correlation was also observed with memory scores from standardized neuropsychological tests. These data are consistent with a proposed link between the late positive repetition effect and conscious memory. On the other hand, the N400 repetition effect was not correlated with episodic memory abilities, but instead indexed an aspect of memory that was intact in the amnesic patients. The preserved N400 repetition effect is an example of preserved memory in amnesia that does not easily fit into the categories of low-level perceptual processing or of motor learning. Instead, the sensitivity of the N400 to both semantic context and repetition may reflect a short-term memory process that serves language comprehension in realtime.

Adult↗

PubMed1999

Mini-Mental State Examination and Mattis Dementia Rating Scale performance differs in Hispanic and non-Hispanic Alzheimer's disease patients.

Little information exists regarding the performance of Spanish-speaking versus English-speaking patients with Alzheimer's disease (AD) on the Mini-Mental State Examination and the Mattis Dementia Rating Scale. In an attempt to identify culturally biased MMSE items or DRS subscales, we matched Spanish-speaking Hispanic and English-speaking non-Hispanic White community-dwelling AD patients by their MMSE scores and examined specific items within each scale. Our findings indicate that Hispanic AD patients perform significantly worse than non-Hispanics in terms of total DRS score, scores on the DRS subscales for Conceptualization and Memory, and on serial subtraction (or backward spelling item) of the MMSE. While mildly to moderately demented Hispanic and non-Hispanic patients obtained comparable scores on the DRS, severely impaired Spanish-speaking participants obtained considerably lower DRS scores than their English-speaking counterparts. The discrepancy in the DRS scores of the severely impaired Hispanic and non-Hispanic examinees might reflect a cultural bias in the test or educational differences between the groups. Alternatively, the DRS may be more sensitive than the MMSE for detecting severe cognitive impairment in Hispanic patients.

Aged↗

PubMed1999

Differential decline in word generation from phonemic and semantic categories during the course of Alzheimer's disease: implications for the integrity of semantic memory.

The ability to generate words from phonemic (i.e., words beginning with 'F,' 'A,' and 'S') and semantic (i.e., animals, fruits, and vegetables) categories was assessed longitudinally in patients with Alzheimer's disease (AD; N = 59) and normal controls (NC; N = 59). Patients with AD performed worse than NC participants on both tasks at each of 4 annual evaluations and exhibited greater impairment relative to controls on the semantic-category task than on the phonemic-category task. In addition, the performance of the patients with AD declined over time on both tasks, but the rate of decline was faster on the semantic-category than on the phonemic-category task. Examination of individual responses across the annual evaluations revealed that patients with AD were more consistent than NC participants in failing to generate previously produced semantic-category, but not phonemic-category, items in all years following the 1st year in which the item was not produced. These results are consistent with the notion that patients with AD suffer a gradual deterioration of the organization and content of semantic memory as the disease progresses.

Aged↗