Distinct profiles of brain and cognitive changes in the very old with Alzheimer disease.

OBJECTIVE: To determine whether age-standardized brain morphometric and cognitive profiles differ in young-old (aged 60-75 years) and very-old (aged 80-91 years) patients with Alzheimer disease (AD). METHODS: Using a case-control retrospective design, we compared hippocampal volume and cortical gray matter thickness in areas known to be affected by AD in 105 patients with AD and 125 healthy control (HC) participants divided into young-old and very-old subgroups. Brain morphometric and cognitive scores of the AD groups were standardized to their respective age-appropriate HC subgroup and then compared. RESULTS: Several cognitive domains (executive function, immediate memory, and attention/processing speed) were less abnormal in the very old with AD than in the young old with AD. Similarly, the very old with AD showed less severe cortical thinning than the young old with AD in the left posterior cingulate cortex, right lateral temporal cortex, and bilateral parietal cortex and in overall cortical thickness. This effect is partially explained by an age-related decrease in cortical thickness in these brain regions in the HC participants. CONCLUSIONS: The typical pattern of AD-related cognitive and morphometric changes seen in the young old appear to be less salient in the very old. Thus, mild cases of AD in the very old may go undetected if one expects to see the prototypical pattern and severity of cognitive or brain changes that occur in the young old with AD. These results underscore the importance of interpreting neuropsychological test performance and morphometric brain measures in reference to the individual's age.

Psychometric comparison of standard and computerized administration of the Alzheimer's Disease Assessment Scale: Cognitive Subscale (ADASCog).

BACKGROUND: The Alzheimer's Disease Assessment Scale ­ Cognitive Subscale (ADAS-Cog) has become the de facto gold standard for assessing the efficacy of anti-dementia treatments. However, manual administration of the ADAS-Cog is subject to procedural inconsistencies, including scoring and transcription errors, which can introduce unwanted variance and compromise data quality within and across sites and trials. To address such concerns, a computerized version was developed that integrates, rather than replaces, the examiner, standardizes administration, and uses electronic data capture at the point of patient contact. The examiner can control administration and pacing, pause or repeat digitized instructions, score verbal report and overt behavioral performance, and freely interact with the subject. PURPOSE: To conduct psychometric comparisons of traditional, paper-based administration of the standard ADAS-Cog (sADAS) with examiner- assisted administration of the computerized ADAS-Cog (cADAS). METHODS: Eighty-eight patients (39M; 49F) with mild to moderate Alzheimer's disease were tested on three occasions with each version over a period of one year with one month between paired visits. RESULTS: Intraclass Correlation Coefficients (ICC) comparisons between sADAS and cADAS were significant for total score (ICC=0.96) and all subscores (ICCs ranged 0.78-0.93), with no significant differences on paired t-tests. The mean ICCs across cADAS scores for test-retest reliability for short-term (mean ICC=0.96) and long-term (mean ICC=0.91) comparisons were significantly higher than across sADAS scores (mean ICCs were 0.87 and 0.84, respectively). CONCLUSIONS: These results indicate that examiner-assisted, computerized administration is equivalent to traditional, paper-based administration, and shows significantly greater test-retest reliability.

Global clinical dementia rating of 0.5 in MCI masks variability related to level of function.

OBJECTIVE: To evaluate whether ratings on Clinical Dementia Rating (CDR) items related to instrumental activities of daily living (IADL) are associated with cognitive or brain morphometric characteristics of participants with mild cognitive impairment (MCI) and global CDR scores of 0.5. METHODS: Baseline cognitive and morphometric data were analyzed for 283 individuals with MCI who were divided into 2 groups (impaired and intact) based on their scores on the 3 CDR categories assessing IADL. Rates of progression to Alzheimer disease (AD) over 2 years were also compared in the 2 groups. RESULTS: The impaired IADL MCI group showed a more widespread pattern of gray matter loss involving frontal and parietal regions, worse episodic memory and executive functions, and a higher percentage of individuals progressing to AD than the relatively intact IADL MCI group. CONCLUSIONS: The results demonstrate the importance of considering functional information captured by the CDR when evaluating individuals with MCI, even though it is not given equal weight in the assignment of the global CDR score. Worse impairment on IADL items was associated with greater involvement of brain regions beyond the mesial temporal lobe. The conventional practice of relying on the global CDR score as currently computed underutilizes valuable IADL information available in the scale, and may delay identification of an important subset of individuals with MCI who are at higher risk of clinical decline.

Elevated pulse pressure is associated with age-related decline in language ability.

Recent research suggests that pulse pressure (PP), a putative marker of vascular integrity, may be associated with brain microvascular damage and age-related cognitive decline. Thus, the present study examined the relationship between PP and cognition in a sample of healthy nondemented older adults. One hundred nine participants were administered neurological and neuropsychological evaluations and determined to be nondemented. Regression analyses were used to examine the relationships among pulse pressure (PP) [systolic blood pressure (SBP)--diastolic blood pressure (DBP)], age, and cognition. PP and related measures were inversely correlated with global cognitive functioning and scores on a composite measure of language function, even after adjusting for age, education, and relevant vascular risk factors. Results indicate that increases in the pulsatile component of blood pressure may convey added risk of global cognitive decline and specific impairment in language abilities.

Multi-modal imaging predicts memory performance in normal aging and cognitive decline.

This study (n=161) related morphometric MR imaging, FDG-PET and APOE genotype to memory scores in normal controls (NC), mild cognitive impairment (MCI) and Alzheimer's disease (AD). Stepwise regression analyses focused on morphometric and metabolic characteristics of the episodic memory network: hippocampus, entorhinal, parahippocampal, retrosplenial, posterior cingulate, precuneus, inferior parietal, and lateral orbitofrontal cortices. In NC, hippocampal metabolism predicted learning; entorhinal metabolism predicted recognition; and hippocampal metabolism predicted recall. In MCI, thickness of the entorhinal and precuneus cortices predicted learning, while parahippocampal metabolism predicted recognition. In AD, posterior cingulate cortical thickness predicted learning, while APOE genotype predicted recognition. In the total sample, hippocampal volume and metabolism, cortical thickness of the precuneus, and inferior parietal metabolism predicted learning; hippocampal volume and metabolism, parahippocampal thickness and APOE genotype predicted recognition. Imaging methods appear complementary and differentially sensitive to memory in health and disease. Medial temporal and parietal metabolism and morphometry best explained memory variance. Medial temporal characteristics were related to learning, recall and recognition, while parietal structures only predicted learning.

Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer's disease supports retrogenesis.

The retrogenesis model of Alzheimer's disease (AD) posits that white matter (WM) degeneration follows a pattern that is the reverse of myelogenesis. Using diffusion tensor imaging (DTI) to test this model, we predicted greater loss of microstructural integrity in late-myelinating WM fiber pathways in AD patients than in healthy older adults, whereas differences in early-myelinating WM fiber pathways were not expected. We compared 16 AD patients and 14 demographically-matched healthy older adults with a whole-brain approach via tract-based spatial statistics (TBSS), and a region of interest (ROI) approach targeting early-myelinating (posterior limb of internal capsule, cerebral peduncles) and late-myelinating (inferior longitudinal fasciculus [ILF], superior longitudinal fasciculus [SLF]) fiber pathways. Permutation-based voxelwise analysis supported the retrogenesis model. There was significantly lower fractional anisotropy (FA) in AD patients compared to healthy older adults in late-myelinating but not early-myelinating pathways. These group differences appeared to be driven by loss of myelin integrity based on our finding of greater radial diffusion in AD than in healthy elderly. ROI analyses were generally in agreement with whole-brain findings, with significantly lower FA and increased radial diffusion in the ILF in the AD group. Consistent with the retrogenesis model, AD patients showed demonstrable changes in late-myelinating WM fiber pathways. Given greater change in the ILF than the SLF, wallerian degeneration secondary to cortical atrophy may also be a contributing mechanism. Knowledge of the pattern of WM microstructural changes in AD and its underlying mechanisms may contribute to earlier detection and intervention in at-risk groups.

Patients with MCI and N400 or P600 abnormalities are at very high risk for conversion to dementia.

OBJECTIVE: We sought cognitive event-related potential (ERP) biomarkers of disease progression and subsequent conversion to dementia in mild cognitive impairment (MCI). BACKGROUND: Two ERP components, the P600 and N400, are sensitive to abnormal episodic/declarative memory and semantic processing. When congruous category-exemplars are repeated, smaller P600s (relative to initial presentation) are normally elicited. Repetitions of semantically incongruous words yield smaller N400 amplitude. In mild Alzheimer disease (AD), abnormalities of both the N400 and P600 repetition effects are present, suggesting a widespread failure of synaptic plasticity. METHODS: Patients with amnestic MCI (n = 32) were longitudinally studied annually with an ERP paradigm in which semantically congruous (50%) and incongruous target words are repeated 10 to 140 seconds after initial presentation. ERP data were analyzed to contrast MCI-to-AD converters (within 3 years) vs nonconverters, using split-plot analyses of variance. RESULTS: A statistically significant P600 congruous word repetition effect was found only in the nonconverter group (F = 9.9, p = 0.005 vs MCI converters). This effect correlated with verbal memory measures. Repetition of incongruous words produced a significant N400 amplitude attenuation (across right-hemisphere sites) in nonconverters, but not in converters. Patients with MCI with abnormal/reduced N400 or P600 word repetition effects had an 87 to 88% likelihood of dementia within 3 years while those with normal/spared N400 and P600 repetition effects had only an 11 to 27% likelihood. CONCLUSIONS: Abnormalities of the P600 or N400 in mild cognitive impairment are associated with an increased risk of subsequent conversion to Alzheimer disease (AD). These event-related potential components may offer useful biomarkers for the detection and staging of very early AD.

Cycad exposure and risk of dementia, MCI, and PDC in the Chamorro population of Guam.

OBJECTIVE: To study cycad-derived products as possible risk factors for dementia, mild cognitive impairment (MCI), and parkinsonism-dementia complex (PDC) on Guam. METHODS: Complete risk factor data from in-person interviews of 166 cases of Guam dementia, 50 cases of amnestic MCI, and 21 cases of PDC were compared with 1,581 controls in the base population regarding exposure to cycad-derived products from a traditional food (fadang), consumption of fruit bats, and use of cycad-derived topical medicine. RESULTS: Adjusted odds ratios (ORs) and 95% CIs for picking, processing, and eating fadang in young adulthood ranged from 1.42 (1.05 to 1.91) to 2.87 (1.48 to 5.56) and were consistently elevated and significant across all three diagnostic outcomes. Associations independent of exposure in young adulthood were for picking (OR 0.78, 95% CI 0.64 to 0.96) and processing (OR 0.77, 95% CI 0.63 to 0.94) fadang in childhood with Guam dementia. Men showed stronger and more consistent relations across exposure groups in young adulthood compared with women. No associations were found for consumption of fruit bats or exposure to cycad used as a topical medicine for any of the outcomes. Estimated adjusted population attributable risks suggest that exposure to eating fadang in young adulthood incurred the highest attributable risk percent. CONCLUSIONS: Environmental lifestyle and diet may contribute to the etiology of neurodegenerative diseases in the native population of Guam.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.