Medical decision-making capacity in mild cognitive impairment: a 3-year longitudinal study.

OBJECTIVE: To investigate longitudinal change in the medical decision-making capacity (MDC) of patients with amnestic mild cognitive impairment (MCI) under different consent standards. METHODS: Eighty-eight healthy older controls and 116 patients with MCI were administered the Capacity to Consent to Treatment Instrument at baseline and at 1 to 3 (mean = 1.7) annual follow-up visits thereafter. Covariate-adjusted random coefficient regressions were used to examine differences in MDC trajectories across MCI and control participants, as well as to investigate the impact of conversion to Alzheimer disease on MCI patients' MDC trajectories. RESULTS: At baseline, MCI patients performed significantly below controls only on the three clinically relevant standards of appreciation, reasoning, and understanding. Compared with controls, MCI patients experienced significant declines over time on understanding but not on any other consent standard. Conversion affected both the elevation (a decrease in performance) and slope (acceleration in subsequent rate of decline) of MCI patients' MDC trajectories on understanding. A trend emerged for conversion to be associated with a performance decrease on reasoning in the MCI group. CONCLUSIONS: Medical decision-making capacity (MDC) decline in mild cognitive impairment (MCI) is a relatively slow but detectable process. Over a 3-year period, patients with amnestic MCI show progressive decline in the ability to understand consent information. This decline accelerates after conversion to Alzheimer disease (AD), reflecting increasing vulnerability to decisional impairment. Clinicians and researchers working with MCI patients should give particular attention to the informed consent process when conversion to AD is suspected or confirmed.

Cognitive models of medical decision-making capacity in patients with mild cognitive impairment.

This study investigated cognitive predictors of medical decision-making capacity (MDC) in patients with amnestic mild cognitive impairment (MCI). A total of 56 healthy controls, 60 patients with MCI, and 31 patients with mild Alzheimer's disease (AD) were administered the Capacity to Consent to Treatment Instrument (CCTI) and a neuropsychological test battery. The CCTI assesses MDC across four established treatment consent standards--S1 (expressing choice), S3 (appreciation), S4 (reasoning), and S5 (understanding)--and one experimental standard [S2] (reasonable choice). Scores on neuropsychological measures were correlated with scores on each CCTI standard. Significant bivariate correlates were subsequently entered into stepwise regression analyses to identity group-specific multivariable predictors of MDC across CCTI standards. Different multivariable cognitive models emerged across groups and consent standards. For the MCI group, measures of short-term verbal memory were key predictors of MDC for each of the three clinically relevant standards (S3, S4, and S5). Secondary predictors were measures of executive function. In contrast, in the mild AD group, measures tapping executive function and processing speed were primary predictors of S3, S4, and S5. MDC in patients with MCI is supported primarily by short-term verbal memory. The findings demonstrate the impact of amnestic deficits on MDC in patients with MCI.

Medical decision-making capacity in patients with mild cognitive impairment.

OBJECTIVES: To empirically assess the capacity of patients with amnestic mild cognitive impairment (MCI) to consent to medical treatment under different consent standards (Ss). METHODS: Participants were 56 healthy controls, 60 patients with MCI, and 31 patients with mild Alzheimer disease (AD). Each participant was administered the Capacity to Consent to Treatment Instrument (CCTI) and a comprehensive neuropsychological battery. Group differences in performance on the CCTI and neuropsychological variables were examined. In addition, the capacity status (capable, marginally capable, or incapable) of each MCI participant on each CCTI standard was examined using cut scores derived from control performance. RESULTS: Patients with MCI performed comparably to controls on minimal consent standards requiring merely expressing a treatment choice (S1) or making the reasonable treatment choice [S2], but significantly below controls on the three clinically relevant standards of appreciation (S3), reasoning (S4), and understanding (S5). In turn, the MCI group performed significantly better than the mild AD group on [S2], S4, and S5. Regarding capacity status, patients with MCI showed a progressive pattern of capacity compromise (marginally capable and incapable outcomes) related to stringency of consent standard. CONCLUSIONS: Patients with amnestic mild cognitive impairment (MCI) demonstrate significant impairments on clinically relevant abilities associated with capacity to consent to treatment. In obtaining informed consent, clinicians and researchers working with patients with MCI must consider the likelihood that many of these patients may have impairments in consent capacity related to their amnestic disorder and related cognitive impairments.

The role of cholinergic systems in visuospatial processing and memory.

Few studies have specifically addressed the cholinergic role in visuospatial memory. In the present study, we employed a randomized double-blind repeated measures design to investigate the effects of scopolamine on Judgement of Line Orientation (JLO) and two distinct visuospatial memory tasks. Complex Figures (CF) is a test of drawn reproduction similar to the Rey complex figure. The Spatial Array Memory Test (SAMT) is a two-dimensional free-recall visuospatial test which minimizes constructive skills and allows sensitive measurement of placement errors. Scopolamine impaired performance on JLO and CF. However, no effects of scopolamine on SAMT were apparent even though the SAMT is sensitive to aging and right temporal-lobe lesions. Selective effects of scopolamine on focused versus distributed attention may account for these differential results.

Effects of carbamazepine and phenytoin on EEG and memory in healthy adults.

Using a randomized, double-blind, cross-over design, we investigated the effects of carbamazepine (CBZ) and phenytoin (PHT) on memory and spectral EEG components in 15 healthy adults. Each subject was treated with each drug for 1 month, separated by a 1-month washout. Evaluations were conducted at baseline, at the end of each treatment month, and 1 month after the last treatment phase. EEG was collected during an eyes-closed resting condition and a verbal memory activation task. Spectral analysis of the EEG in the nondrug conditions showed that the memory task significantly reduced theta components and increased delta components. As compared with nondrug conditions, the antiepileptic drugs (AEDs) significantly impaired memory performance and produced mild EEG slowing. Memory performance did not differ statistically between the AEDs, but minor differences in spectral EEG components were noted. The results suggest that differences in the cognitive and EEG effects of CBZ and PHT are not clinically significant.

Reproducibility of P3.

The P3 event-related potential has been widely employed in both clinical and research investigations. In the present study, P3 latency and amplitude intersession reliability were evaluated in 4 sessions over an average of 33 days in 24 healthy adults using the P3 tonal oddball paradigm. Mean group latencies ranged from 302-305 ms and mean amplitudes ranged from 7.75-8.87 microV. No significant group differences were found across sessions for latency or amplitude. Intrasubject variability was large; the 95% confidence interval for the difference between the means of two combined sessions was +/- 20 ms for latency and +/- 4.63 microV for amplitude. The results suggest that P3 latency and amplitude are reliable and reproducible over weeks for groups, but have greater variability for individuals.

Comparative cognitive effects of carbamazepine and phenytoin in healthy adults.

We investigated neuropsychological effects of carbamazepine and phenytoin in 21 healthy adults using a randomized, double-blind, double-crossover design and treating each subject with each drug for 1 month, separated by a 1-month washout. There were neuropsychological evaluations at baseline, the end of each treatment month, and 1 month after the last treatment phase. Cognitive measures included Symbol Digit Modalities Test, Selective Reminding Test, Complex Figures, Paced Auditory Serial Addition Test, Stroop, Finger Tapping, Grooved Pegboard, Choice Reaction Time, P3 Event-Related Potential, Hopkins Symptom Checklist, and Profile of Mood States (POMS). Compared with nondrug conditions, the anticonvulsants significantly impaired Stroop, Choice Reaction Time, Grooved Pegboard, Hopkins, and POMS. Employing anticonvulsant blood levels as covariates, there were only two significant differences between drugs, one in favor of carbamazepine (ie, Finger Tapping) and one in favor of phenytoin (ie, Stroop). The results suggest that differences in cognitive effects of carbamazepine and phenytoin are not clinically significant.

Effects of scopolamine on visual evoked potentials in aging and dementia.

The unusual combination of a normal pattern reversal VEP and a delayed flash VEP has been reported in patients with dementia of Alzheimer's type (DAT). Hyoscine hydrobromide has been reported to produce a similar VEP abnormality in young, healthy subjects. In the present study, we assessed the relative sensitivity of DAT patients and healthy young, middle-aged and elderly subjects to temporary cholinergic blockade. We report VEP latency values following 3 doses of scopolamine and after a peripheral anticholinergic agent. Flash P2 latency was not significantly slower in DAT patients than in the healthy elderly. Scopolamine increased P2 latency in the young controls but did not affect any other group. The pattern reversal P100 was normal in DAT, and a significant increase in latency occurred following scopolamine administration in both the control and patient groups.

Unilateral cerebral inactivation produces differential left/right heart rate responses.

We studied heart rate following unilateral hemispheric inactivation by intracarotid amobarbital in 25 patients undergoing preoperative evaluation for epilepsy surgery. Heart rate increased after left hemisphere inactivation, but decreased following right hemisphere inactivation. The results are consistent with differential left/right cerebral hemispheric effects on autonomic function, and appear related to functional and anatomic asymmetries in both the central and peripheral nervous systems.

Asymmetry in clinical features of drug-induced parkinsonism.

In clinical practice, distinguishing drug-induced parkinsonism from Parkinson's disease may be difficult. Asymmetry is generally not felt to be common in drug-induced parkinsonism. The authors investigated asymmetry of signs and symptoms in 20 patients with drug-induced parkinsonism. Tremor was identified in seven patients, slowness in five, and mixed symptoms in eight. A notable asymmetry of signs was seen in six patients. As in Parkinson's disease, subgroups seem to exist within the group of patients with drug-induced parkinsonism, and an asymmetry of signs and symptoms is not uncommon.