Frederick W. Bylsma

Psychological examination of traumatic encephalopathy

Abstract This paper incorporates a direct English translation of two key French papers on the Rey (1941) Complex Figure as modified proceduraly by Osterrieth (1944). The descriptions of the technique in the two original papers are supplemented by a commentary on the current use of the technique in clinical practice.

Age at onset of Alzheimer's disease Relation to pattern of cognitive dysfunction and rate of decline

We examined the pattern of cognitive impairment and rate of cognitive and functional decline as a function of age at symptom onset in 127 patients with probable Alzheimers disease (AD). At baseline, early-onset (before age 65) and late-onset groups were mildly and comparably impaired on the modified Mini-Mental State Examination (mMMS) and the Blessed Dementia Rating Scale-Part 1 (BDRS). Repeated-measures analysis of variance revealed significantly more rapid decline in early-onset subjects over a 2-year follow-up period. Multivariate linear regression analyses indicated that age at symptom onset strongly predicted rate of decline on the mMMS and the BDRS, even after controlling for symptom duration, gender, family history of dementia, and baseline mMMS and BDRS scores. Early- and late-onset AD subjects also differed in terms of pattern of performance on the mMMS. Early-onset subjects scored significantly lower than late-onset subjects on attentional items of the mMMS at baseline and follow-up. Conversely, late-onset subjects scored significantly lower than early-onset subjects on memory and naming items at baseline, and the two groups were comparable on these tasks at follow-up. Results provide longitudinal evidence of more rapid cognitive and functional decline in subjects with early-onset AD and suggest that early-onset AD may be characterized by predominant impairment of attentional skills.

Longitudinal change in basal ganglia volume in patients with Huntington's disease

Article abstract-Cross-sectional MRI studies demonstrating an association between caudate atrophy and symptom severity and duration of symptoms in patients with Huntingtons disease (HD) have been assumed to reflect longitudinal changes in basal ganglia, but such neuropathologic progression has never been directly demonstrated. Subjects in the current study were 23 HD patients at various stages of the disorder who had two MRI images at least 10 months apart (mean interimage interval = 20.8 months). We measured volumes of caudate, putamen, and globus pallidus blind to the order of the images. For each structure, we calculated a change score by subtracting the volume obtained on the follow-up imaging from that obtained on the initial imaging. Results indicated significant decreases over time in caudate, putamen, and total basal ganglia volume. Age at onset and length of trinucleotide repeat correlated significantly with amount of volume change in caudate and total basal ganglia, even after controlling for length of interimage interval, duration of disease, and measures of symptom severity. Amount of change in basal ganglia structures was not significantly correlated with neurologic symptom severity at the time of the initial imaging or duration of symptoms. This is the first longitudinal MRI study to document progressive basal ganglia atrophy in HD, and suggests that quantitative neuroimaging with serial MRI may be useful in monitoring effectiveness of potential treatments. In addition, demonstration of greater rate of basal ganglia atrophy in patients with earlier symptom onset suggests that treatment effects may be more quickly observed in this subgroup of patients than in the general HD population. NEUROLOGY 1997;48: 394-399

Frontal lobe volume in patients with Huntington's disease

Neuropathologic and neuroimaging studies have suggested that frontal lobes are affected in Huntingtons disease (HD), and that atrophy in this region may be associated with some of the cognitive impairment and clinical decline observed in patients with HD. We measured gray and white matter volumes within the frontal lobes on MRI for 20 patients with HD (10 mildly affected and 10 moderately affected) and 20 age- and sex-matched control subjects. We also correlated frontal lobe measurements with measures of symptom severity and cognitive function. Patients who were mildly affected had frontal lobe volumes (both gray and white matter) essentially identical to those of control subjects, despite clearly abnormal basal ganglia. Patients who were moderately affected demonstrated significant reductions in total frontal lobe volume (17%) and frontal white matter volume (28%). Frontal lobe white matter volume reductions, but not total frontal lobe volume reductions, were disproportionately greater than overall brain volume reductions (17%). Frontal lobe volume correlated with symptom severity and general cognitive function, but these correlations did not remain significant after taking into account total brain volume. We conclude that cognitive impairment and symptom severity are associated with frontal lobe atrophy, but this association is not specific to the frontal lobes. Frontal lobe atrophy (like total brain atrophy) occurs in later stages of increasing HD symptom severity and this atrophy primarily involves white matter.

Trinucleotide repeat length and clinical progression in Huntington's disease

We examined the relationship between length of the trinucleotide (CAG) repeat at IT-15 and clinical progression of Huntingtons disease in 46 mildly to moderately affected patients over a 2-year interval. Patients were divided into those with short mutations (37 to 46 repeats; n equals 25) and those with long mutations (more than equals 47 repeats, n equals 21). Patients with long repeat lengths had earlier age at onset and were younger and less functionally impaired than those with short repeats at the initial visit, but the groups did not differ in severity of neurologic or cognitive impairment. However, the long-repeat group displayed significantly greater decline in both neurologic and cognitive functioning over the 2-year follow-up period. The length of the CAG repeat correlated highly with age at onset (r equals minus 0.72, p less than 0.001) and was a strong predictor of decline in both neurologic and cognitive function. The mechanism of gene action, and the means by which longer expansions result in a more malignant disease process, remain to be elucidated. NEUROLOGY 1996,46 527-531

DEMENTIA AND DRIVING: AN ATTEMPT AT CONSENSUS

Summary:The number of older drivers in Sweden will be rapidly increasing during the next decades. A possible relationship exists between the increased relative crash risk of older drivers and the prevalence of age-related diseases such as dementia. However, a clear-cut policy for evaluating driving competence in demented persons is still lacking. In recognition of this fact, the Swedish National Road Administration invited a group of researchers to formulate a consensus on the issue of driving and dementia. This consensus document is aimed at providing primary care physicians with practical advice concerning the assessment of cognitive status in relation to driving. Suggestions are based on a review of existing research and discuss the use of general and driving-specific sources of information available to the physician. Consensus was reached on the statement that a diagnosis of moderate to severe dementia precludes driving and that certain individuals with mild dementia should be considered for a specialized assessment of their driving competence.

Cognitive and motor correlates of everyday functioning in early Huntington's disease

The present study documents the prevalence of deficits in the ability to carry out a variety of activities of daily living in early Huntingtons disease (HD), along with the associated neuropsychological and motor deficits. Eighty patients with HD were assessed with the Huntingtons Disease-Activities of Daily Living Questionnaire (HD-ADL). Sixty-seven patients also completed a comprehensive assessment of cognitive and voluntary motor functioning and chorea. The latter measures were correlated with HD-ADL total score and with most HDADL items, but not with those items dealing with marital and family relationship adjustment. Findings suggest that psychomotor speed and the ability to regulate attention may be particularly important determinants of everyday functioning in mild HD. Consistent with previously reported observations, this appears to be true even after accounting for individual differences in the severity of chorea and voluntary motor impairment.

Disengagement of attention in schizophrenia

We compared covert shift of visual attention in patients with schizophrenia or bipolar disorder, both in states of remission, to normal controls to examine the persistence of lateralized attentional deficits into nonpsychotic states. Although patients were slower in all conditions than normals, there was no difference in pattern of attentional shift among the groups. This suggests that the left-hemisphere deficit in shift of covert attention in schizophrenia may be limited to periods of florid illness.

Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study.

SummaryMagnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntingtons disease (HD). A factor analysis of the neuropsychological test scores provided three factors: a memory/speed-of-processing factor, a “frontal” factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the “frontal” or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD.

Stability of performance on the Hopkins Verbal Learning Test

Stability of performance on the Hopkins Verbal Learning Test (HVLT) was assessed in 45 healthy elderly subjects over a 9-month period. Stability coefficients were moderate but statistically significant for total recall (r = 0.50), true-positive recognitions (r = 0.66), and false-positive errors (r = 0.42). These correlations are comparable to test-retest correlations reported for other clinical tests of verbal memory (e.g., Logical Memory subtest of the Wechsler Memory Scale-Revised, California Verbal Learning Test) and are sufficient for its clinical use.