The utility of a non-verbal prospective memory measure as a sensitive marker for early-stage Alzheimer's disease in Hong Kong.

ABSTRACT Background: With the proportion of older adults in Hong Kong projected to double in size in the next 30 years, it is important to develop measures for detecting individuals in the earliest stage of Alzheimer's disease (AD, 0.5 in Clinical Dementia Rating, CDR). We tested the utility of a non-verbal prospective memory task (PM, ability to remember what one has to do when a specific event occurs in the future) as an early marker for AD in Hong Kong Chinese. Methods: A large community dwelling sample of older adults who are healthy controls (CDR 0, N = 125), in the earliest stage of AD (CDR 0.5, N = 125), or with mild AD (CDR 1, N = 30) participated in this study. Their reaction time/accuracy data were analyzed by mixed-factor analyses of variance to compare the performance of the three CDR groups. Logistic regression analyses were performed to test the discriminative power of these measures for CDR 0 versus 0.5 participants. Results: Prospective memory performance declined as a function of AD severity: CDR 0 > CDR 0.5 > CDR 1, suggesting the effects of early-stage AD and AD progression on PM. After partialling out the variance explained by psychometric measures (e.g., ADAS-Cog), reaction time/accuracy measures that reflected the PM still significantly discriminated between CDR 0 versus 0.5 participants in most of the cases. Conclusion: The effectiveness of PM measures in discriminating individuals in the earliest stage of AD from healthy older adults suggests that these measures should be further developed as tools for early-stage AD discrimination.

Genetic factors of reaction time performance: DRD4 7-repeat allele associated with slower responses.

Twin studies indicate substantial inherited components in cognitive abilities. One of the most extensively studied candidate genes of cognitive functioning is the dopamine D4 receptor gene (DRD4), which has been suggested to be related to attentional disorders. Based on reaction time data of 245 Caucasians participating in different cognitive tasks, slower responses characterized the group with the 7-repeat allele. This effect was present in both sexes and was not because of fatigue. To our knowledge, this is the first report on significant association (P = 0.0001) between the DRD4 variable number of tandem repeat (VNTR) polymorphism and response latencies in a non-clinical adult sample. Other studied dopaminergic polymorphisms did not show an association with reaction time. These results illustrate that speed-of-performance measures derived from multiple reaction time tasks using standardization procedures could be promising tools to detect unique genetic effects in the background of cognitive abilities.

Task-dependent modulation of regions in the left inferior frontal cortex during semantic processing.

To distinguish areas involved in the processing of word meaning (semantics) from other regions involved in lexical processing more generally, subjects were scanned with positron emission tomography (PET) while performing lexical tasks, three of which required varying degrees of semantic analysis and one that required phonological analysis. Three closely apposed regions in the left inferior frontal cortex and one in the right cerebellum were significantly active above baseline in the semantic tasks, but not in the nonsemantic task. The activity in two of the frontal regions was modulated by the difficulty of the semantic judgment. Other regions, including some in the left temporal cortex and the cerebellum, were active across all four language tasks. Thus, in addition to a number of regions known to be active during language processing, regions in the left inferior frontal cortex were specifically recruited during semantic processing in a task-dependent manner. A region in the right cerebellum may be functionally related to those in the left inferior frontal cortex. Discussion focuses on the implications of these results for current views regarding neural substrates of semantic processing.

Subjective frequency estimates for 2,938 monosyllabic words.

Subjective frequency estimates for large sample of monosyllabic English words were collected from 574 young adults (undergraduate students) and from a separate group of 1,590 adults of varying ages and educational backgrounds. Estimates from the latter group were collected via the internet. In addition, 90 healthy older adults provided estimates for a random sample of 480 of these words. All groups rated words with respect to the estimated frequency of encounters of each word on a 7-point scale, ranging from never encountered to encountered several times a day. The young and older groups also rated each word with respect to the frequency of encounters in different perceptual domains (e.g., reading, hearing, writing, or speaking). The results of regression analyses indicated that objective log frequency and meaningfulness accounted for most of the variance in subjective frequency estimates, whereas neighborhood size accounted for the least amount of variance in the ratings. The predictive power of log frequency and meaningfulness were dependent on the level of subjective frequency estimates. Meaningfulness was a better predictor of subjective frequency for uncommon words, whereas log frequency was a better predictor of subjective frequency for common words. Our discussion focuses on the utility of subjective frequency estimates compared with other estimates of familiarity. The raw subjective frequency data for all words are available at http://www.artsci.wustl.edu/dbalota/labpub.html.

Semantic, phonological, and hybrid veridical and false memories in healthy older adults and in individuals with dementia of the Alzheimer type.

Five groups of participants (young, healthy old, healthy old-old, very mild dementia of the Alzheimer type [DAT], and mild DAT) studied 12-item lists of words that converged on a critical nonpresented word (cold) semantically (chill, frost, warm, ice), phonologically (code, told, fold, old), or in a hybrid list of both (chill, told, warm, old). The results indicate that (a) veridical recall decreased with age and dementia; (b) recall of the nonpresented items increased with age and remained fairly stable across dementia; and (c) false recall varied by list type, with hybrid lists producing superadditive effects. For hybrid lists, individuals with DAT were 3 times more likely to recall the critical nonpresented word than a studied word. When false memory was considered as a proportion of veridical memory, there was an increase in relative false memory as a function of age and dementia. Results are discussed in terms of age- and dementia-related changes in attention and memory.

Building episodic connections: changes in episodic priming with age and dementia.

Previous studies of associative encoding that used explicit retrieval tasks have shown both age- and dementia of the Alzheimer type (DAT)-related declines, but such results may be biased by group differences in explicit retrieval. In the present experiment, the authors assessed implicit associative encoding for 25 younger adults (ages 18-25), 73 healthy older adults (ages 59-91), and 65 adults with DAT (ages 59-91) during a speeded word-naming task using an episodic priming measure. Episodic priming refers to the facilitation in responding to a target word after repetition of both words in a prime-target pair, in comparison with simple repetition of the target word with a new prime on each presentation. In contrast with other studies of implicit associative encoding that did not use an implicit episodic priming measure, the present study found both age- and DAT-related declines in associative encoding under conditions of massed learning trials.

The attentional control of lexical processing pathways: reversing the word frequency effect.

In two experiments, we investigated the influence of word frequency in speeded word naming and in a relatively novel regularization task in which participants were required to pronounce words on the basis of spelling-to-sound correspondences instead of giving their normal pronunciations (e.g., pronounce pint so that it rhymes with hint). Participants were presented high- and low-frequency regular words and exception words, along with a set of nonwords. The results indicated that there was a normal word frequency effect (i.e., high-frequency words faster than low-frequency words) in the standard speeded naming task, whereas, for the regularization task, the word frequency effect was reversed for regular words, even though the regular words were pronounced in an identical fashion in both the normal naming and the regularization tasks. This reversal of the word frequency effect was not obtained for the exception words. The discussion focuses on the implication of these results for attentional control models of lexical processing.

Factors influencing word naming in younger and older adults.

The present study examined age differences in the influence of 3 factors that previous research has shown to influence word-naming performance. The influence of word frequency, orthographic length, and orthographic neighborhood measures was examined using large-scale regression analyses on the naming latencies for 2,820 words. Thirty-one younger adults and 29 older adults named all of these words, and age differences in the influence of these factors were examined. The results revealed that all 3 factors predicted reliable amounts of variance in word-naming latencies for both groups. However, older adults showed a larger influence of word frequency and reduced influences of orthographic length and orthographic neighborhood density compared with younger adults. Overall, these results suggest that lexical level factors increase in influence in older adults whereas sublexical factors decrease in influence.

Auditory habituation in young and older adults: the verbal transformation effect.

In 3 experiments, auditory massed repetition was used to examine age-related differences in habituation by means of the verbal transformation paradigm. Participants heard 10 words (5 high frequency and 5 low frequency), each presented 180 times, and they reported perceived changes in the repeated words (verbal transformations). In these experiments, older adults reported fewer illusory percepts than young adults. Older adults' loss of auditory acuity and slowing of processing, stimulus degradation (in young adults), and instructions biasing the report of these illusory percepts did not account for the fewer illusory percepts reported by the older adults. These findings suggest that older adults' reduced susceptibility to habituation arises from centrally located declines in the transmission of information within the word-recognition pathway. The discussion focuses on the implications that these age-related declines may have on word identification during on-line speech perception.

Levels of selective attention revealed through analyses of response time distributions.

The present research examines the nature of the interference effects in a number of selective attention tasks. All of these tasks result in interference in performance by presenting information that is irrelevant to task performance but competes for selection. The interference from this competing information slows the response time (RT) of participants relative to a condition where the competition is minimized. The authors use a convolution of an exponential and a Gaussian (ex-Gaussian) distribution to examine the influence of interference on the characteristics of RT distributions. Consistent with previous research, the authors show that interference in the Stroop task is reflected by both the Gaussian and exponential portions of the ex-Gaussian. In contrast, in 4 experiments they show that several other interference tasks evidence interference that is reflected only in the Gaussian portion of the ex-Gaussian distribution. The authors suggest that these differences reflect the operation of different selection mechanisms, and they examine how sequential sampling models accommodate these effects.

Priming and attentional control of lexical and sublexical pathways during naming.

A modified priming task was used to investigate whether skilled readers are able to adjust the degree to which lexical and sublexical information contribute to naming. On each trial, participants named 5 low-frequency exception word primes or 5 nonword primes before a target. The low-frequency exception word primes should have produced a greater dependence on lexical information, whereas the nonword primes should have produced a greater dependence on sublexical information. Across 4 experiments, the effects of lexicality, regularity, frequency, and imageability were all modulated in predictable ways on the basis of the notion that the primes directed attention to specific processing pathways. It is argued that these results are consistent with an attentional control hypothesis.

Individual differences in information-processing rate and amount: implications for group differences in response latency.

Research on group differences in response latency often has as its goal the detection of Group x Treatment interactions. However, accumulating evidence suggests that response latencies for different groups are often linearly related, leading to an increased likelihood of finding spurious overadditive interactions in which the slower group produces a larger treatment effect. The authors propose a rate-amount model that predicts linear relationships between individuals and that includes global processing parameters based on large-scale group differences in information processing. These global processing parameters may be used to linearly transform response latencies from different individuals to a common information-processing scale so that small-scale group differences in information processing may be isolated. The authors recommend linear regression and z-score transformations that may be used to augment traditional analyses of raw response latencies.

Word frequency, repetition, and lexicality effects in word recognition tasks: beyond measures of central tendency.

Response time (RT) distributions obtained from 3 word recognition experiments were analyzed by fitting an ex-Gaussian function to the empirical data to determine the main effects and interactive influences of word frequency, repetition, and lexicality on the nature of the underlying distributions. The ex-Gaussian analysis allows one to determine if a manipulation simply shifts the response time (RT) distribution, produces a skewing of the RT distribution, or both. In contrast to naming performance, the lexical decision results indicated that the main effects and interactions of word frequency, repetition, and lexicality primarily reflect increased skewing of the RT distributions, as opposed to simple shifts of the RT distributions. The implications of the results were interpreted within a hybrid 2-stage model of lexical decision performance.

Effects of lexicality, frequency, and spelling-to-sound consistency on the functional anatomy of reading.

Functional neuroimaging was used to investigate three factors that affect reading performance: first, whether a stimulus is a word or pronounceable non-word (lexicality), second, how often a word is encountered (frequency), and third, whether the pronunciation has a predictable spelling-to-sound correspondence (consistency). Comparisons between word naming (reading) and visual fixation scans revealed stimulus-related activation differences in seven regions. A left frontal region showed effects of consistency and lexicality, indicating a role in orthographic to phonological transformation. Motor cortex showed an effect of consistency bilaterally, suggesting that motoric processes beyond high-level representations of word phonology influence reading performance. Implications for the integration of these results into theoretical models of word reading are discussed.

Cross-modal semantic and homograph priming in healthy young, healthy old, and in Alzheimer's disease individuals.

Two experiments are reported that explore the influence of strength of the prime-target relationship on the observed priming effects in young, healthy old, and individuals diagnosed with dementia of the Alzheimer type (DAT). In Experiment 1, participants were auditorily presented primes (FURNITURE) and after varying delays presented visual targets that were (1) high-strength related (e.g., SOFA), (2) low-strength related (e.g., RUG), or (3) unrelated control words (e.g., COW or DEER). The results indicated that the DAT individuals produced relatively larger priming effects that both the young and the healthy old, but these data could be accommodated by increases in effect size due to general slowing of response latencies. In Experiment 2, the same cross-modal priming paradigm was used with ambiguous words presented as primes (e.g., BANK) and either high-dominant (e.g., MONEY) or low-dominant (e.g., RIVER) words as targets. The results of Experiment 2 produced a qualitatively distinct pattern of priming that indicated DAT individuals only produced priming for high-dominant targets and not for low-dominant targets, whereas, the healthy control groups produced equivalent priming for both high- and low-dominant targets. The discussion focuses on the implication that these results have for the interpretation of semantic priming effects, in general, along with implications for the apparent semantic memory loss in DAT individuals.

Relating anatomy to function in Alzheimer's disease: neuropsychological profiles predict regional neuropathology 5 years later.

Neuropsychological profiles were assessed in a large group of nondemented control subjects (n = 261) and individuals with dementia of the Alzheimer type (DAT) (n = 407) by subjecting their psychometric test results to a factor analysis. Nondemented control subjects were functionally homogeneous with only one factor accounting for the results. The results of the factor analysis on the very mild DAT and mild DAT groups, however, yielded a mental control/frontal factor, a memory-verbal/temporal factor, and a visuospatial/parietal factor. Forty-one of the original set of participants came to autopsy an average of 5.1 years after psychometric testing and had neurofibrillary tangles, total senile plaques, and cored senile plaques estimated from frontal, temporal, and parietal regions. The results of correlations indicated that the relative burden of cored senile plaques was systematically related to the three psychometric factors. These results suggest a connection between the specific functions as defined by neuropsychological measures and specific neuropathology occurring in associated areas of cortex.

Explorations of Cohen, Dunbar, and McClelland's (1990) connectionist model of Stroop performance.

The J. D. Cohen, K. Dunbar, and J. L. McClelland (1990) model of Stroop task performance is used to model data from a study by D. H. Spielder, D. A. Balota, and M. E. Faust (1996). The results indicate that the model fails to capture overall differences between word reading and color naming latencies when set size is increased beyond 2 response alternatives. Further empirical evidence is presented that suggests that the influence of increasing response set size in Stroop task performance is to increase the difference between overall color naming and word reading, which is in direct opposition to the decrease produced by the Cohen et al. architecture. Although the Cohen et al. model provides a useful description of meaning-level interference effects, the qualitative differences between word reading and color naming preclude a model that uses identical architectures for each process, such as that of Cohen et al., to fully capture performance in the Stroop task.

Inhibition of visual and conceptual information during reading in healthy aging and Alzheimer's disease.

The present experiment examined the effect of distraction on reading ability and comprehension in healthy aging and early stage dementia of the Alzheimer type (DAT). A modified version of the reading task used by Connelly, Hasher, and Zacks (1991, Experiment 2) was employed. Healthy young, healthy old (60-79 years, and 80 years and over), very mild DAT, and mild DAT participants read passages aloud and then answered comprehension questions. There were four experimental conditions in which distracting information was embedded in the text: (control), orthographic (xxxxx), lexical (unrelated), and semantic (related). The results indicated that there was greater susceptibility to increasing levels of distraction with age and increasing dementia severity. Moreover, there was a substantial slowdown in reading time in mild DAT when text was used as distracting information, especially conceptually related text. Furthermore, mild DAT participants were more likely to make false alarms in comprehension performance (i.e., choose as an answer the incorrect response which contained the related distracting information). Thus, in early stage DAT, there appears to be increased difficulty inhibiting partially activated information, especially when it is related to the relevant information being processed.