Malcolm B. Dick

The effects of age, education, and ethnicity on verbal fluency

A group of 317 healthy participants between 54 and 99 years of age performed a verbal fluency task. The participants included Chinese, Hispanic, and Vietnamese immigrants, as well as White and African American English speakers. They were given 1 min to name as many animals as possible in their native language. The results showed that more animal names were produced by younger people and those with more education. Language background was also an important factor: The Vietnamese produced the most animal names and the Spanish speakers produced the fewest. The exaggerated difference between these two groups is attributed to the fact that Vietnamese animal names are short (predominantly 1 syllable) while the Spanish animal names are longer than any other language in this study (2 and 3 syllables per word). Finally, although the ethnic groups named different animals, and appeared to vary in the variety of animal names they used, these factors did not affect overall verbal fluency performance.

Walking stabilizes cognitive functioning in Alzheimer's disease (AD) across one year

AD is a public health epidemic, which seriously impacts cognition, mood and daily activities; however, one type of activity, exercise, has been shown to alter these states. Accordingly, we sought to investigate the relationship between exercise and mood, in early-stage AD patients (N=104) from California, over a 1-year period. Patients completed the Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), and Blessed-Roth Dementia Rating Scale (BRDRS), while their caregivers completed the Yale Physical Activity Survey (YALE), Profile of Mood States (POMS), the Neuropsychiatric Inventory (NPI) and Functional Abilities Questionnaire (FAQ). Approximately half of the participants were female, from a variety of ethnic groups (Caucasian=69.8%; Latino/Hispanic Americans=20.1%). Our results demonstrated that the patients spent little time engaged in physical activity in general, their overall activity levels decreased over time, and this was paired with a change in global cognition (e.g., MMSE total score) and affect/mood (e.g., POMS score). Patients were parsed into Active and Sedentary groups based on their Yale profiles, with Active participants engaged in walking activities, weekly, over 1 year. Here, Sedentary patients had a significant decline in MMSE scores, while the Active patients had an attenuation in global cognitive decline. Importantly, among the Active AD patients, those individuals who engaged in walking for more than 2 h/week had a significant improvement in MMSE scores. Structured clinical trials which seek to increase the amount of time AD patients were engaged in walking activities and evaluate the nature and scope of beneficial effects in the brain are warranted.

Neuropsychological data in nondemented oldest old: The 90+ Study

Although the oldest old are the fastest growing segment of the population, little is known about their cognitive performance. Our aim was to compile a relatively brief test battery that could be completed by a majority of individuals aged 90 or over, compensates for sensory losses, and incorporates previously validated, standardized, and accessible instruments. Means, standard deviations, and percentiles for 10 neuropsychological tests covering multiple cognitive domains are reported for 339 nondemented members of the 90+ Study. Cognitive performance declined with age for two-thirds of the tests. Performance on some tests was also affected by gender, education, and depression scores.

Caspase-Cleaved Tau Accumulation in Neurodegenerative Diseases Associated with Tau and α-Synuclein Pathology

Alzheimer’s disease (AD), Pick’s disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are diseases associated with the accumulation of tau or α-synuclein. In AD, β-amyloid (Aβ)-associated caspase activation and cleavage of tau at Asp421 (ΔTau) may be an early step in neurofibrillary tangle (NFT) formation. To examine whether ΔTau accumulates in other diseases not characterized by extracellular Aβ accumulation, we examined PiD, PSP, and CBD cases in comparison to those without extensive tau accumulation including frontotemporal lobar degeneration without Pick bodies (FTLD) and control cases. Additionally, we studied ΔTau accumulation in DLB cases associated with intracellular α-synuclein. ΔTau was observed in all disease cases except non-PiD FTLD and controls. These results demonstrate that the accumulation of ΔTau may represent a common pathway associated with abnormal accumulation of intracellular tau or α-synuclein and may be relatively less dependent on the extracellular accumulation of Aβ in non-AD dementias.

Facilitating acquisition and transfer of a continuous motor task in healthy older adults and patients with Alzheimer's disease.

This study examined the acquisition and transfer of a fine motor skill, namely the rotary pursuit, in 99 patients with Alzheimers disease (AD) and 100 normal controls (NCs). To identify optimal learning strategies, the authors had participants practice the rotary pursuit under constant, blocked, random, or no training conditions. Transfer was assessed using speeds that were different from those practiced during acquisition. AD patients and NCs receiving constant practice outperformed their peers in the blocked and random conditions during acquisition. Whereas all 3 types of practice facilitated transfer in the NCs, AD patients only benefited from constant practice. The inability of the AD patients to benefit from variable practice suggests that these individuals may have difficulty accessing and/or forming motor schemas.

Practice Effects on Motor Control in Healthy Seniors and Patients with Mild Cognitive Impairment and Alzheimer's Disease

ABSTRACT This research was designed to test the hypothesis that motor practice can enhance the capabilities of motor control in healthy controls (NC) and patients with a diagnosis of probable Alzheimers disease (AD) and mild cognitive impairment (MCI), and consequently results in better motor performance. Approximately half of the subjects in the NC (n = 31), AD (n = 28), and MCI (n = 29) either received or did not receive practice on a task of fast and accurate arm movement with a digitizer. Changes in movement time (MT), movement smoothness (jerk), and percentage of primary submovement (PPS) were recorded and compared among the three groups across six blocks of trials (baseline and five training sessions). For all subjects, practice improved motor functions as reflected by faster and smoother motor execution, as well as a greater proportion of programming control. Compared to unaffected matched controls, AD and MCI subjects exhibited a greater reduction in movement jerk due to practice. Movement time and PPS data revealed that motor practice appeared to reduce the use of “on-line” correction adopted by the AD or MCI patients while performing the aiming movements. Evidently, their arm movements were quicker, smoother, and temporally more consistent than their untrained peers. The findings of this study shed light on how MCI and AD may affect motor control mechanisms, and suggest possible therapeutic interventions aimed at improving motor functioning in these impaired individuals.

Decreased levels of C1q in cerebrospinal fluid of living Alzheimer patients correlate with disease state

Recent reports that complement proteins comprising the classical pathway are associated with senile plaques suggest that activation of the classical complement cascade in Alzheimers disease tissue results in bystander cell lysis and may contribute to AD neuropathology. Analysis of cerebrospinal fluid may prove to be a useful means of detecting changes in immunological activity in the brain. We use an enzyme-linked immunosorbent assay to measure levels of C1q, a subunit of the classical complement cascade, in the CSF of patients clinically diagnosed with possible or probable AD. Significantly lower levels of C1q were detected in the CSF of the Alzheimer group as compared to control CSF [AD: mu = 268 ng/ml, SD = 84; non-AD: mu = 340 ng/ml, SD = 76; F(1, 44) = 5.84, p = 0.02]. Diminished performance on global measures of mental status such as the Mini-Mental State Exam (R = 0.45; p = 0.0072) and Blesseds Information, Memory, and Concentration test (R = 0.42; p = 0.0138) showed high correlations with decreased C1q levels. More specific measures of cognitive function, such as word recall (R = 0.42; p = 0.012), word recognition (R = 0.52; p = 0.0017) and delayed recall (R = 0.45; p = 0.0062) memory tasks also correlated strongly with decreased C1q levels.

Two-Stage Machine Learning model for guideline development

We present a Two-Stage Machine Learning (ML) model as a data mining method to develop practice guidelines and apply it to the problem of dementia staging. Dementia staging in clinical settings is at present complex and highly subjective because of the ambiguities and the complicated nature of existing guidelines. Our model abstracts the two-stage process used by physicians to arrive at the global Clinical Dementia Rating Scale (CDRS) score. The model incorporates learning intermediate concepts (CDRS category scores) in the first stage that then become the feature space for the second stage (global CDRS score). The sample consisted of 678 patients evaluated in the Alzheimers Disease Research Center at the University of California, Irvine. The demographic variables, functional and cognitive test results used by physicians for the task of dementia severity staging were used as input to the machine learning algorithms. Decision tree learners and rule inducers (C4.5, Cart, C4.5 rules) were selected for our study as they give expressive models, and Naive Bayes was used as a baseline algorithm for comparison purposes. We first learned the six CDRS category scores (memory, orientation, judgement and problem solving, personal care, home and hobbies, and community affairs). These learned CDRS category scores were then used to learn the global CDRS scores. The Two-Stage ML model classified as well as or better than the published inter-rater agreements for both the category and global CDRS scoring by dementia experts. Furthermore, for the most critical distinction, normal versus very mildly impaired, the Two-Stage ML model was 28.1 and 6.6% more accurate than published performances by domain experts. Our study of the CDRS examined one of the largest, most diverse samples in the literature, suggesting that our findings are robust. The Two-Stage ML model also identified a CDRS category, Judgment and Problem Solving, which has low classification accuracy similar to published reports. Since this CDRS category appears to be mainly responsible for misclassification of the global CDRS score when it occurs, further attribute and algorithm research on the Judgment and Problem Solving CDRS score could improve its accuracy as well as that of the global CDRS score.

Alterations in regional brain volume and individual MRI-guided perfusion in normal control, stable mild cognitive impairment, and MCI-AD converter.

Regional differences in tissue volume and perfusion in brains of individuals with mild cognitive impairment (MCI) versus normal healthy age-matched controls (NC), and the differences between MCI-AD converters and stable MCI patients were investigated. MRI and SPECT scans were performed on 13 MCI (74+6 years) and 12 NC (75+4 years). Of the MCI patients, 10 were followed for up to three years and 4 subsequently converted to Alzheimers disease (AD). Episodic memory function was assessed using tests of delayed recall for word lists and stories. The volume reductions and hypoperfusion were mainly confined to the medial temporal lobe (MTL) of MCI patients and associated with worse scores on memory tests. Perfusion in the corpus callosum and the gray matter of frontal, lateral temporal, parietal or occipital lobe was not significantly affected in MCI. The 4 MCI-AD converters had relatively low MTL structural volume and perfusion compared to their stable peers.

Contextual Interference and Motor Skill Learning in Alzheimer’s Disease

This study examined the acquisition, retention, and transfer of a gross motor skill, namely, tossing, in 84 moderate-to-severely demented patients with Alzheimer’s disease (AD) and 72 healthy elderly controls. To identify optimal learning strategies, participants received 10 weeks of training under 1 of 5 practice conditions: constant, variable-parameter, variable-program, variable-combined, or no training. Constant practice was the only training condition that significantly enhanced learning and near transfer in AD patients. In comparison, all 4 types of training facilitated acquisition and near transfer in the healthy controls, with variable-combined practice being the most beneficial. The superiority of the variable practice conditions in the healthy controls supports both Schmidt’s (1975) variability of practice hypothesis and contextual interference theory. The inability of AD patients to benefit from variable forms of practice suggests that these impaired individuals may have difficulty accessing and/or forming motor schemas.