Endpoints for Pre-Dementia AD Trials: A Report from the EU/US/CTAD Task Force.

For Alzheimer's disease treatment trials that focus on the pre-dementia stage of disease, outcome measures are needed that will enable assessment of disease progression in patients who are clinically normal. The EU/US CTAD Task Force, an international collaboration of investigators from industry, academia, non-profit foundations, and regulatory agencies, met in Philadelphia, Pennsylvania, USA, on November 19, 2014 to discuss existing and novel outcome assessments that may be useful in pre-dementia trials. Composite measures that assess changes in episodic memory, executive function, global cognition, and global function have recently been developed by a number of groups and appear to be sensitive at this stage. Functional measures that involve real-life complex tasks also appear to capture early subtle changes in pre-dementia subjects and have the advantage of representing clinically meaningful change. Patient reported outcomes and novel CSF and imaging biomarkers have also shown promise. More studies are needed to validate all of these tests in the pre-dementia population. Many of them have been incorporated as exploratory measures in ongoing or planned trials.

Cationic carbosilane dendrimers and oligonucleotide binding: an energetic affair.

Generation 2 cationic carbosilane dendrimers hold great promise as internalizing agents for gene therapy as they present low toxicity and retain and internalize the genetic material as an oligonucleotide or siRNA. In this work we carried out complete in silico structural and energetical characterization of the interactions of a set of G2 carbosilane dendrimers, showing different affinity towards two single strand oligonucleotide (ODN) sequences in vitro. Our simulations predict that these four dendrimers and the relevant ODN complexes are characterized by similar size and shape, and that the molecule-specific ODN binding ability can be rationalized only by considering a critical molecular design parameter: the normalized effective binding energy ΔG(bind,eff)/N(eff), i.e. the performance of each active individual dendrimer branch directly involved in a binding interaction.

The sigma enigma: in vitro/in silico site-directed mutagenesis studies unveil σ1 receptor ligand binding.

The σ1 receptor is an integral membrane protein that shares no homology with other receptor systems, has no unequivocally identified natural ligands, but appears to play critical roles in a wide variety of cell functions. While the number of reports of the possible functions of the σ1 receptor is increasing, almost no information about the three-dimensional structure of the receptor and/or possible modes of interaction of the σ1 protein with its ligands have been described. Here we performed an in vitro/in silico investigation to analyze the molecular interactions of the σ1 receptor with its prototypical agonist (+)-pentazocine. Accordingly, 23 mutant σ1 isoforms were generated, and their interactions with (+)-pentazocine were determined experimentally. All direct and/or indirect effects exerted by the mutant residues on the receptor-agonist interactions were reproduced and rationalized in silico, thus shining new light on the three-dimensional structure of the σ1 receptor and its ligand binding site.

Latent information in fluency lists predicts functional decline in persons at risk for Alzheimer disease.

OBJECTIVE: We constructed random forest classifiers employing either the traditional method of scoring semantic fluency word lists or new methods. These classifiers were then compared in terms of their ability to diagnose Alzheimer disease (AD) or to prognosticate among individuals along the continuum from cognitively normal (CN) through mild cognitive impairment (MCI) to AD. METHOD: Semantic fluency lists from 44 cognitively normal elderly individuals, 80 MCI patients, and 41 AD patients were transcribed into electronic text files and scored by four methods: traditional raw scores, clustering and switching scores, "generalized" versions of clustering and switching, and a method based on independent components analysis (ICA). Random forest classifiers based on raw scores were compared to "augmented" classifiers that incorporated newer scoring methods. Outcome variables included AD diagnosis at baseline, MCI conversion, increase in Clinical Dementia Rating-Sum of Boxes (CDR-SOB) score, or decrease in Financial Capacity Instrument (FCI) score. Receiver operating characteristic (ROC) curves were constructed for each classifier and the area under the curve (AUC) was calculated. We compared AUC between raw and augmented classifiers using Delong's test and assessed validity and reliability of the augmented classifier. RESULTS: Augmented classifiers outperformed classifiers based on raw scores for the outcome measures AD diagnosis (AUC .97 vs. .95), MCI conversion (AUC .91 vs. .77), CDR-SOB increase (AUC .90 vs. .79), and FCI decrease (AUC .89 vs. .72). Measures of validity and stability over time support the use of the method. CONCLUSION: Latent information in semantic fluency word lists is useful for predicting cognitive and functional decline among elderly individuals at increased risk for developing AD. Modern machine learning methods may incorporate latent information to enhance the diagnostic value of semantic fluency raw scores. These methods could yield information valuable for patient care and clinical trial design with a relatively small investment of time and money.

Lexical factors and cerebral regions influencing verbal fluency performance in MCI.

OBJECTIVE: To evaluate assumptions regarding semantic (noun), verb, and letter fluency in mild cognitive impairment (MCI) and Alzheimer disease (AD) using novel techniques for measuring word similarity in fluency lists and a region of interest (ROI) analysis of gray matter correlates. METHOD: Fifty-eight individuals with normal cognition (NC, n=25), MCI (n=23), or AD (n=10) underwent neuropsychological tests, including 10 verbal fluency tasks (three letter tasks [F, A, S], six noun categories [animals, water creatures, fruits and vegetables, tools, vehicles, boats], and verbs). All pairs of words generated by each participant on each task were compared in terms of semantic (meaning), orthographic (spelling), and phonemic (pronunciation) similarity. We used mixed-effects logistic regression to determine which lexical factors were predictive of word adjacency within the lists. Associations between each fluency raw score and gray matter volumes in sixteen ROIs were identified by means of multiple linear regression. We evaluated causal models for both types of analyses to specify the contributions of diagnosis and various mediator variables to the outcomes of word adjacency and fluency raw score. RESULTS: Semantic similarity between words emerged as the strongest predictor of word adjacency for all fluency tasks, including the letter fluency tasks. Semantic similarity mediated the effect of cognitive impairment on word adjacency only for three fluency tasks employing a biological cue. Orthographic similarity was predictive of word adjacency for the A and S tasks, while phonemic similarity was predictive only for the S task and one semantic task (vehicles). The ROI analysis revealed different patterns of correlations among the various fluency tasks, with the most common associations in the right lower temporal and bilateral dorsal frontal regions. Following correction with gray matter volumes from the opposite hemisphere, significant associations persisted for animals, vehicles, and a composite nouns score in the left inferior frontal gyrus, but for letter A, letter S, and a composite FAS score in the right inferior frontal gyrus. These regressions also revealed a lateralized association of the left subcortical nuclei with all letter fluency scores and fruits and vegetables fluency, and an association of the right lower temporal ROI with letter A, FAS, and verb fluency. Gray matter volume in several bihemispheric ROIs (left dorsal frontal, right lower temporal, right occipital, and bilateral mesial temporal) mediated the relationship between cognitive impairment and fluency for fruits and vegetables. Gray matter volume in the right lower temporal ROI mediated the relationship between cognitive impairment and five fluency raw scores (animals, fruits and vegetables, tools, verbs, and the composite nouns score). CONCLUSION: Semantic memory exerts the strongest influence on word adjacency in letter fluency as well as semantic verbal fluency tasks. Orthography is a stronger influence than pronunciation. All types of fluency task raw scores (letter, noun, and verb) correlate with cerebral regions known to support verbal or nonverbal semantic memory. The findings emphasize the contribution of right hemisphere regions to fluency task performance, particularly for verb and letter fluency. The relationship between diagnosis and semantic fluency performance is mediated by semantic similarity of words and by gray matter volume in the right lower temporal region.

Tell me something I do not know. Multiscale molecular modeling of dendrimer/ dendron organization and self-assembly in gene therapy.

Due to the relative easy synthesis and commercial availability, nanovectors based on dendrimers and dendrons are among the most utilized non-viral vectors for gene transfer. Contextually, recent advances in molecular simulations and computer architectures not only allow for accurate predictions of many structural, energetical, and eventual self-assembly features of these nanocarriers per se, but are able to yield vital (and perhaps otherwise unattainable) molecular information about the interactions of these nanovectors with their nucleic acid cargoes. In the present work, we aim at reviewing our own efforts in the field of multiscale molecular modeling of these interesting materials. In particular, our originally developed computational recipes will be presented, and the link between simulations and experiments will be described and discussed in detail. This review is written by computational scientists for experimental scientists, with the specific purpose of illustrating the potentiality of these methodologies and the usefulness of multiscale molecular modeling as an innovative and complementary tool in their current research.

Treatment consent capacity in patients with traumatic brain injury across a range of injury severity.

OBJECTIVE: To investigate medical decision-making capacity (MDC) in patients with acute traumatic brain injury (TBI) across a range of injury severity. METHODS: We evaluated MDC cross-sectionally 1 month after injury in 40 healthy controls and 86 patients with TBI stratified by injury severity (28 mild [mTBI], 15 complicated mild [cmTBI], 43 moderate/severe [msevTBI]). We compared group performance on the Capacity to Consent to Treatment Instrument and its 5 consent standards (expressing choice, reasonable choice, appreciation, reasoning, understanding). Capacity impairment ratings (no impairment, mild/moderate impairment, severe impairment) on the consent standards were also assigned to each participant with TBI using cut scores referenced to control performance. RESULTS: One month after injury, the mTBI group performed equivalently to controls on all consent standards. In contrast, the cmTBI group was impaired relative to controls on the understanding standard. No differences emerged between the mTBI and cmTBI groups. The msevTBI group was impaired on almost all standards relative to both control and mTBI groups, and on the understanding standard relative to the cmTBI group. Capacity compromise (mild/moderate or severe impairment ratings) on the 3 clinically complex standards (understanding, reasoning, appreciation) occurred in 10%-30% of patients with mTBI, 50% of patients with cmTBI, and 50%-80% of patients with msevTBI. CONCLUSIONS: One month following injury, MDC is largely intact in patients with mTBI, but is impaired in patients with cmTBI and msevTBI. Impaired MDC is prevalent in acute TBI and is strongly related to injury severity.

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.

Medical decision-making in neurodegenerative disease: mild AD and PD with cognitive impairment.

The authors compared medical decision-making capacity in patients with mild Alzheimer disease (AD), Parkinson disease (PD) with cognitive impairment, and older controls. Relative to controls and patients with PD, patients with AD were impaired on the consent ability of understanding the medical treatment situation and choices. Patients with PD were impaired on the consent ability of electing a treatment choice.

Impaired financial abilities in mild cognitive impairment: a direct assessment approach.

OBJECTIVES: To assess financial capacity in patients with mild cognitive impairment (MCI) using a standardized psychometric capacity measure. METHODS: Participants were 21 cognitively normal older controls, 21 patients with amnestic MCI, and 22 patients with mild AD. The Financial Capacity Instrument (FCI), a psychometric capacity measure consisting of 18 financial ability tests (tasks), 9 domains (activities), and 2 total scores, was administered to participants along with a battery of neuropsychological tests sensitive to dementia. Group differences were examined on the neuropsychological and financial capacity variables. RESULTS: Relative to controls, the MCI group demonstrated impairments in episodic memory, and also semantic knowledge, executive function, written arithmetic, and spatial attention. MCI participants demonstrated impairments in FCI domains of conceptual knowledge, cash transactions, bank statement management, and bill payment, and in overall financial capacity. The control and MCI groups performed significantly better than patients with AD on most financial capacity and cognitive measures. CONCLUSIONS: On direct assessment, patients with amnestic MCI as a group demonstrate impairments across a range of financial abilities. These impairments are mild and may only apply to a subset of patients with MCI. However, existing diagnostic criteria for MCI should be applied flexibly to include mild impairments in higher order activities of daily life such as financial capacity.

Competency to consent to medical treatment in cognitively impaired patients with Parkinson's disease.

OBJECTIVES: To investigate capacity to consent to medical treatment (competency) in cognitively impaired patients with PD. BACKGROUND: Although competency has been studied empirically in patients with cortical dementia (AD), no empirical studies have examined competency in patients with PD or other subcortical neurodegenerative disorders. METHODS: Patients with PD with cognitive impairment (n = 20) and older controls (n = 20) were compared using a standardized competency measure (Capacity to Consent to Treatment Instrument [CCTI]) and neuropsychological test measures. The CCTI tests competency performance and assigns outcomes (capable, marginally capable, incapable) under four different legal standards (LS). RESULTS: Patients with PD performed below controls on the four LS: capacity to evidence a treatment choice (LS1) (p < 0.03), capacity to appreciate consequences of a treatment choice (LS3) (p < 0.03), capacity to provide rational reasons for a treatment choice (LS4) (p < 0.0001), and capacity to understand the treatment situation and choices (LS5) (p < 0.0001). With respect to competency outcomes, patients with PD demonstrated increasing compromise (marginally capable or incapable outcomes) across the four standards: LS1 (25%), LS3 (45%), LS4 (55%), and LS5 (80%). In the PD group, simple measures of executive function (the Executive Interview) and to a lesser extent memory/orientation (Dementia Rating Scale, Memory subscale) were key predictors of competency performance and outcome on the LS. CONCLUSIONS: Cognitively impaired patients with PD are likely to have impaired consent capacity, and are at risk of losing competency over the course of their neurodegenerative illness. Patients with PD have particular difficulty meeting more stringent, clinically relevant competency standards that tap reasoning skills and comprehension of treatment information. Executive dysfunction appears to be a primary neurocognitive mechanism for competency loss in PD.

Informed consent, competency, and the neurologist.

BACKGROUND: Obtaining informed consent to treatment is an important medical-legal and clinical aspect of neurological practice. REVIEW SUMMARY: This review discusses the doctrine of informed consent and its role in neurological practice. We first provide an overview of the informed consent doctrine and discuss its historical origins and current modern form. The three component elements of informed consent--being informed, voluntary, and competent--are presented, with a focus placed on the competency element. The increasingly important role of informed consent in everyday neurological practice is profiled, with particular emphasis on patients with dementia. Recent empirical research is presented on loss of consent capacity (competency) in patients with Alzheimer's disease and Parkinson's disease. Finally, a conceptually based approach to clinical assessment of competency is presented to assist neurologists dealing with these issues. CONCLUSIONS: The increasing prevalence of patients with neurodegenerative disorders in neurological practice heightens the importance of obtaining valid informed consent to treatment.

The Severe Mini-Mental State Examination: a new neuropsychologic instrument for the bedside assessment of severely impaired patients with Alzheimer disease.

The bedside and office assessment of cognitive abilities in moderately to severely impaired patients with Alzheimer disease could be enhanced by a well-standardized instrument. The authors' group has developed such an instrument (i.e., Severe Mini-Mental State Examination; SMMSE) to assess this population. Based on the Folstein Mini-Mental State Examination (MMSE), the SMMSE, which totals 30 points, was designed to briefly assess cognitive domains relatively preserved in moderate to severe Alzheimer disease. One hundred eighty-two patients with possible or probable Alzheimer disease were administered both the MMSE and SMMSE. Performances on the SMMSE and MMSE were found to correlate significantly only when MMSE fell below 9 points (p < 0.0001). However, as performance on the MMSE approached floor levels, patients continued to score at half maximal levels on the SMMSE. Functional staging with the Clinical Dementia Rating Scale and the Global Deterioration Scale also were found to significantly correlate with performance on the SMMSE (p < 0.001). Test-retest performance on both the SMMSE and MMSE was relatively stable over a period of 5 months. Inter-rater reliability of the SMMSE was excellent. These results suggest that the SMMSE has both construct and criterion validity for assessing severely impaired Alzheimer disease patients. Our results also suggest that the SMMSE may be a useful instrument for assessing severely impaired patients at the bedside and in the office.

Consistency of physicians' legal standard and personal judgments of competency in patients with Alzheimer's disease.

OBJECTIVES: To investigate the consistency of physician judgments of treatment consent capacity (competency) for patients with Alzheimer's disease (AD) when specific legal standards (LS) for competency are used, and to identify the LS most clinically relevant to experienced physicians. DESIGN: Control and AD patient participants were videotaped being administered a measure of capacity to consent to medical treatment. Study physicians viewed videotapes of these assessments individually and made competency judgments for each participant under different LS followed by their own personal judgment of competency. SETTING: A university medical center. PARTICIPANTS: Participants were 10 older controls and 21 patients with AD (10 with mild and 11 with moderate AD). Five physicians with experience assessing the competency of AD patients were recruited from the geriatric psychiatry, geriatric medicine, and neurology services of a university medical center. MEASUREMENTS: The 31 participants were videotaped performing on a measure of treatment consent capacity (Capacity to Consent to Treatment Instrument) (CCTI). The CCTI consists of two clinical vignettes (A-neoplasm and B-cardiac) that test competency under five LS. Vignette A and B assessments were videotaped separately for each participant (total videotapes for sample = 62). Each study physician viewed each videotaped vignette individually, made judgments under each of the LS (competent or incompetent), and then made his/her own personal competency judgment. Physicians were blinded to participant diagnosis. Within participant group, consistency of physician judgments was evaluated across LS and personal judgments using percentage agreement and kappa. Agreement between personal and LS judgments for the AD group was evaluated for each physician using logistic regression. RESULTS: As expected, physicians as a group generally demonstrated very high percentage agreement in their LS and personal competency judgments for the control group. For the AD group, mean percentage judgment agreement among physicians ranged from a high of 84% (LS1) (evidencing a treatment choice) to a low of 67% (LS3) (appreciating consequences of treatment choice). Mean percentage agreement for personal competency judgments was 76%. For the AD sample, kappa analyses for physicians as a group demonstrated significant agreement not attributable to chance for LS5 (understanding treatment situation/choices) (k = 0.57, P = .001), LS4 (providing rational reasons for treatment choice) (k = 0.39, P = .04), and also for personal judgments (k = 0.48, P = .009). Analysis of LS judgment agreement within physician indicated that physicians applied the LS as discrete standards. Within-physician and for the AD sample, personal competency judgments were associated significantly with judgments on LS5 (P = .001), LS4 (P = .004), and LS3 (P < .04). CONCLUSIONS: Experienced physicians demonstrated significant agreement assessing competency in AD patients when judgments were based upon specific legal standards. Personal competency judgments of physicians showed a substantially higher level of agreement than found in a previous study, where specific LS were not used. These results suggest that consistency of physician competency judgments can be enhanced if they are guided by knowledge of specific LS. Physicians' personal competency judgments were most closely associated with comprehension and reasoning LS, the most conservative and clinically appropriate standards for deciding competency.

Cognitive models of physicians' legal standard and personal judgments of competency in patients with Alzheimer's disease.

OBJECTIVES: To investigate measures of patient cognitive abilities as predictors of physician judgments of medical treatment consent capacity (competency) in patients with Alzheimer's disease (AD). DESIGN: Predictor models of legal standards (LS) and personal competency judgments were developed for each study physician using independent neuropsychological test measures and logistic regression analyses. SETTING: A university medical center. PARTICIPANTS: Five physicians with experience assessing the competency of AD patients were recruited to make competency judgments of videotaped vignettes from 10 older controls and 21 patients with AD (10 with mild and 11 with moderate dementia). MEASUREMENTS: The 31 patient and control videotapes of performance on a measure of treatment consent capacity (Capacity to Consent to Treatment Instrument) (CCTI) were rated by the five physicians. The CCTI consists of two clinical vignettes (A-neoplasm and B-cardiac) that test competency under five LS. Each study physician viewed each vignette videotape individually, made judgments of competent or incompetent under each of the LS, and then made his/her own personal competency judgment. Physicians were blinded to participant diagnosis and neuropsychological test performance. Stepwise logistic regression was conducted to identify cognitive predictors of each physician's LS and personal competency judgments for Vignette A using the full sample (n = 31). Classification logistic regression analysis was used to determine how well these cognitive predictor models classified each physician's competency judgments for Vignette A. These classification models were then cross-validated using physician's Vignette B judgments. RESULTS: Cognitive predictor models for Vignette A competency judgments differed across individual physicians, and were related to difficulty of LS and to incompetency outcome rates across LS for AD patients. Measures of semantic knowledge and receptive language predicted judgments under less difficult LS of evidencing a treatment choice (LS1) and making the reasonable treatment choice (LS2). Measures of semantic knowledge, short-term verbal recall, and simple reasoning ability predicted judgments under more difficult and clinically relevant LS of appreciating consequences of a treatment choice (LS3), providing rational reasons for a treatment choice (LS4), and understanding the treatment situation and choices (LSS). Cognitive models for physicians' personal competency judgments were virtually identical to their respective models for LS5 judgments. For AD patients, shortterm memory predictors were associated with high incompetency outcome rates (over 70%), a simple reasoning measure was associated with moderately high incompetency outcome rates (60-70%), and a semantic knowledge measure was associated with lower incompetency outcome rates (30-60%). Overall, single predictor models were relatively robust, correctly classifying an average of 83% of physician judgments for Vignette A and 80% of judgments for Vignette B. CONCLUSIONS: Multiple cognitive functions predicted physicians' LS and personal competency judgments. Declines in semantic knowledge, short-term verbal recall, and simple reasoning ability predicted physicians' judgments on the three most difficult and clinically most relevant LS (LS3-LS5), as well as their personal competency judgments. Our findings suggest that clinical assessment of competency should include evaluation of semantic knowledge, verbal recall, and simple reasoning abilities.

Assessing financial capacity in patients with Alzheimer disease: A conceptual model and prototype instrument.

OBJECTIVE: To investigate financial capacity in patients with Alzheimer disease (AD) using a new theoretical model and prototype psychometric instrument. DESIGN: Cross-sectional comparisons of older control subjects (n=23) and patients with mild (n=30) and moderate AD (n=20). MAIN OUTCOME MEASURES: Financial capacity was measured using the Financial Capacity Instrument, a prototype psychometric instrument that tests financial capacity using 14 tasks of financial ability comprising 6 clinically relevant domains of financial activity: basic monetary skills, financial conceptual knowledge, cash transactions, checkbook management, bank statement management, and financial judgment. RESULTS: The Financial Capacity Instrument tasks and domains showed adequate to excellent internal, interrater, and test-retest reliabilities. At the task level, patients with mild AD performed equivalently with controls on simple tasks such as counting coins/currency and conducting a 1-item grocery purchase, but significantly below controls on more complex tasks such as using a checkbook/register and understanding and using a bank statement. At the domain level, patients with mild AD performed significantly below controls on all domains except basic monetary skills. Patients with moderate AD performed significantly below controls and patients with mild AD on all tasks and domains. Regarding capacity status outcomes (capable, marginally capable, incapable) on domains, patients with mild AD had high proportions of marginally capable or incapable outcomes (range, 47%-87%), particularly on difficult domains like bank statement management (domain 5) and financial judgment (domain 6), but variability in individual outcomes. Patients with moderate AD had almost exclusively incapable outcomes across the 6 domains (range, 90%-100%). CONCLUSIONS: Financial capacity is already significantly impaired in mild AD. Patients with mild AD demonstrate deficits in more complex financial abilities and impairment in most financial activities. Patients with moderate AD demonstrate severe impairment of all financial abilities and activities. The Financial Capacity Instrument has promise as an instrument for assessing domain-level financial activities and task-specific financial abilities in patients with dementia. Arch Neurol. 2000.