Decreased beta-amyloid(1-42) and increased phospho-tau protein levels in the cerebrospinal fluid (CSF) are currently the most accurate chemical neurodiagnostics of sporadic Alzheimer disease (AD). A report (2007) of the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (2006) recommended that biological markers should not be currently requisitioned by primary care physicians in the routine investigation of subjects with memory complaints. Consideration for such testing should prompt patient referral to a specialist engaged in dementia evaluations or a Memory Clinic. The specialist should consider having CSF biomarkers (beta-amyloid(1-42) and phospho-tau) measured at a reputable facility in restricted cases presenting with atypical features and diagnostic confusion, but not as a routine procedure in all individuals with typical sporadic AD phenotypes. We submit that developments in the field of AD biomarker discovery since publication of the 3rd CCCDTD consensus data do not warrant revision of the 2007 recommendations.

Patients with Alzheimer disease (AD) usually experience naming difficulty due to storage and access problems in phonological-lexical representation. Investigating naming response patterns followed by cueing may help us to understand the underlying mechanism of naming deficits in AD. A total of 221 patients with mild cognitive impairment and AD [Clinical Dementia Rating (CDR) 0.5, 1, 2] were included as subjects. Sixty items of the Korean version of the Boston Naming Test were given, and upon failure, semantic/syllabic cues were verbally presented. From the results, even in the CDR 2 group, which is considered to be a moderate stage of AD, syllabic cues significantly facilitated correct responses. Our findings are in contrast with previous studies conducted with English-speaking patients, which reported that phonological-lexical representation may have been disrupted in the moderate stage of AD, and that none of the cues facilitated correct word retrieval. The difference may be ascribed to the fact that direct access to the phonological-lexical representation via syllabic cues was possible in the confrontation naming task performed by the Korean patients. It can be concluded that phonological-lexical representation in moderate stage Korean AD might be partially preserved because syllabic cues in AD patients were effective in facilitating target words.

Recently the senior author and his associates developed a spatiotemporal wavelet-chaos methodology for the analysis of electroencephalograms (EEGs) and their subbands for discovering potential markers of abnormality in Alzheimer disease (AD). In this study, fractal dimension (FD) is used for the evaluation of the dynamical changes in the AD brain. The approach presented in this study is based on the research ideology that nonlinear features, such as FD, may not show significant differences between the AD and the control groups in the band-limited EEG, but may manifest in certain subbands. First, 2 different FD algorithms for computing the fractality of EEGs are investigated and their efficacy for yielding potential mathematical markers of AD is compared. They are Katz FD (KFD) and Higuchi FD. Significant features in different loci and different EEG subbands or band-limited EEG for discrimination of the AD and the control groups are determined by analysis of variation. The most discriminative FD and the corresponding loci and EEG subbands for discriminating between AD and healthy EEGs are discovered. As KFD of all loci in the beta subband showed very high ability (P value <0.001) in discriminating between the groups, all KFDs are abstracted in 1 global KFD by averaging across loci in each of the 2 eyes-closed and eyes-open conditions. This leads to a more robust classification in terms of common variation of electrode positions than a classification based on separate KFDs of certain loci. Finally, based on the 2 global features separately and together, linear discriminant analysis is used to classify EEGs of AD and elderly normal patients. A high accuracy of 99.3% was obtained for the diagnosis of the AD based on the global KFD in the beta-band of the eyes-closed condition with a sensitivity of 100% and a specificity of 97.8%.

OBJECTIVE: To test the hypothesis that frequent cognitive activity predicts slower cognitive decline before dementia onset in Alzheimer disease (AD) and faster decline thereafter. METHODS: As part of a longitudinal cohort study, older residents of a geographically defined population were assessed at 3-year intervals with brief cognitive performance tests from which a composite measure of global cognition was derived. After each wave of testing, a subset was sampled for clinical evaluation. The present analyses are based on 1,157 participants. They were free of dementia at study enrollment at which time they rated frequency of participation in common cognitively stimulating activities from which a previously validated summary measure was derived. They were sampled for clinical evaluation a mean of 5.6 years after enrollment and subsequently followed a mean of 5.7 years with brief cognitive performance testing at 3-year intervals. RESULTS: On clinical evaluation, 614 people had no cognitive impairment, 395 had mild cognitive impairment, and 148 had AD. During follow-up, the annual rate of global cognitive decline in persons without cognitive impairment was reduced by 52% (estimate = 0.029, SE = 0.010, p = 0.003) for each additional point on the cognitive activity scale. In the mild cognitive impairment group, cognitive decline rate was unrelated to cognitive activity (estimate = -0.019, SE = 0.018, p = 0.300). In AD, the mean rate of decline per year increased by 42% (estimate = 0.075, SE = 0.021, p < 0.001) for each point on the cognitive activity scale. CONCLUSION: Mentally stimulating activity in old age appears to compress the cognitive morbidity associated with AD by slowing cognitive decline before dementia onset and hastening it thereafter.

OBJECTIVES: Observational and experimental studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD); however, clinical trials and other observational studies, including the Adult Changes in Thought (ACT) study, show no protection or promotion of AD. The objective of this study is to determine the relationship between common dementia-associated pathologies and mid- to late-life NSAID exposure. METHODS: We examined the association of mid- to late-life NSAID use with neuropathologic findings on 257 autopsies from ACT, a population-based study of brain aging and incident dementia. Cumulative standard daily doses (SDD) of nonselective NSAIDs were determined from >/=10 years of computerized pharmacy dispensing data. Analyses were adjusted for selection bias to broaden generalizability of results to 3,026 eligible participants in the ACT cohort. Seven pathologic indices were evaluated: intermediate or frequent score for neuritic plaques, Braak stages V or VI for neurofibrillary tangles, >2 cerebral microinfarcts, the presence of any neocortical Lewy bodies, any macroscopic infarcts, any amyloid angiopathy, and moderate or severe atherosclerosis. RESULTS: Of the neuropathologic indices evaluated, only neuritic plaque score was significantly increased in participants with greater use of nonselective NSAIDs (p = 0.065), specifically in those with high levels of cumulative use: 1,000-2,000 SDD (adjusted relative risk [RR] 2.16, 95% confidence interval [CI] 1.02-4.25, compared to light/nonuse [<60 SDD]) and >2,000 SDD (adjusted RR 2.37, 95% CI 1.24-4.67). CONCLUSIONS: Increased neuritic plaque accumulation may explain the association between heavy use of nonselective NSAIDs and increased risk of dementia among ACT participants.

OBJECTIVE: To estimate the incidence of early-onset dementia (EOD) and to compare the clinical characteristics of EOD vs late-onset dementia (LOD) in a geographically defined area. METHODS: We used data from the Registry of Dementia of Girona (ReDeGi), an epidemiologic surveillance system of dementia. The ReDeGi is a standardized clinical registry of new dementia cases diagnosed in the 7 hospitals of the Health Region of Girona (Catalonia, Spain), which encompasses an area of 5,517 km(2) and 690,207 inhabitants. EOD cases were defined as those patients residing in the target area at the time of diagnosis who were diagnosed with dementia with an age at onset of symptoms before 65 years. RESULTS: The ReDeGi registered 2,083 patients between January 1, 2007, and December 31, 2009 (6.9% EOD). The incidence rate of EOD for the age range 30-64 was 13.4 cases per 100,000 person-years (95% confidence interval 11.3-15.8). Alzheimer disease was the most frequent cause of EOD (42.4%), followed by secondary dementia (18.1%), vascular dementia (13.8%), and frontotemporal dementia (9.7%). EOD cases at the time of diagnosis were less impaired on the Mini-Mental State Examination and had a greater score on the Blessed Dementia Rating Scale behavior subscale than LOD cases. The frequency of a personal history of depression was higher in EOD cases. CONCLUSIONS: The incidence of EOD was less than 6 cases per 100,000 person-years in the age group 30-49 years; in the age group 50-64 years, the incidence rate was 3-fold higher and doubled with each 5-year increase.

Dementia is a highly prevalent problem causing considerable disability and mortality and exacting great costs to individuals, their families, and society. The 4 most common neurodegenerative disorders that cause dementia-Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and dementia in Parkinson disease-have different underlying etiologies and pathogenetic mechanisms. There is a great need for early diagnostic markers; functional brain imaging may therefore assist in the detection and differential diagnosis of dementia due to neurodegenerative diseases. Functional imaging such as PET allows in vivo imaging of functional brain activity indicating cerebral blood flow and cerebral glucose metabolism, and PET allows imaging of neurotransmitter activity, including that of the cholinergic, dopaminergic, and serotonergic systems. New PET neuroimaging tracers are being developed for detecting pathologic parameters such as amyloid plaque and microglial activity. The development of molecular imaging is important for early diagnosis of dementia, selection of patients for therapies, and evaluation of therapies.

Ordinal and quantitative discrete data are frequent in biomedical and neuropsychological studies. We propose a semi-parametric model for the analysis of the change over time of such data in longitudinal studies. A threshold model is defined where the outcome value depends on the current value of an underlying Gaussian latent process. The latent process model is a Gaussian linear mixed model with a non-parametric function of time, f(t), to model the expected change over time. This model includes random-effects and a stochastic error process to flexibly handle correlation between repeated measures. The function f(t) and all the model parameters are estimated by penalized likelihood using a cubic-spline approximation for f(t). The smoothing parameter is estimated by an approximate cross-validation criterion. Confidence bands may be computed for the estimated curves for the latent process and, using a Monte Carlo approach, for the outcome in its natural scale. The method is applied to the Paquid cohort data to compare the time-course over 14 years of two cognitive scores in a sample of 350 future Alzheimer patients and in a matched sample of healthy subjects. Copyright (c) 2010 John Wiley & Sons, Ltd.

The effects of physical exercise on mental health have been extensively investigated, mainly in older people. Recent studies have looked into the acute effect of exercise on the brain using standardized low-resolution brain electromagnetic tomography (sLORETA). We assessed EEG power and mood changes after 20 min of aerobic exercise in elderly (N = 10) and young (N = 19) healthy individuals. Both groups showed improvement in total mood disturbance (TMD) post exercise (young: P = 0.03; elderly: P = 0.02). Only the young group showed significant improvement in anger (P = 0.05) and vigor (P = 0.006). Comparison pre versus post-exercise for each group separately revealed significant changes in the young group (an increase in alpha, beta-1 and beta-2 activity in Brodmann areas 24, 33 and 23, respectively). However, the elderly group did not show significant changes. An inverse correlation was found between alpha asymmetry and STAI (rs = -0.50; P = 0.029) in the young group. On the other hand, a significant correlation between beta-1 activity and TMD was observed in the elderly group (rs = 0.67; P = 0.045). We conclude that acute exercise can have distinct effects on brain activity and mood variables in young individuals when compared with elderly adults. However, additional studies are necessary to further investigate the role of exercise intensity in these results.

OBJECTIVES:: To provide evidence regarding the clinical efficacy of cognitive rehabilitation (CR) in early-stage Alzheimer disease (AD). DESIGN:: Single-blind randomized controlled trial comparing CR with relaxation therapy and no treatment. SETTING:: Outpatient, community-based setting. PARTICIPANTS:: Sixty-nine individuals (41 women, 28 men; mean age 77.78 years, standard deviation 6.32, range = 56-89) with a diagnosis of AD or mixed AD and vascular dementia and a Mini-Mental State Examination score of 18 or above, and receiving a stable dose of acetylcholinesterase-inhibiting medication. Forty-four family carers also contributed. INTERVENTION:: Eight weekly individual sessions of CR consisting of personalized interventions to address individually relevant goals supported by components addressing practical aids and strategies, techniques for learning new information, practice in maintaining attention and concentration, and techniques for stress management. MEASUREMENTS:: The primary outcomes were goal performance and satisfaction, assessed using the Canadian Occupational Performance Measure. Questionnaires assessing mood, quality of life and carer strain, and a brief neuropsychological test battery were also administered. A subset of participants underwent functional magnetic resonance imaging (fMRI). RESULTS:: CR produced significant improvement in ratings of goal performance and satisfaction, whereas scores in the other two groups did not change. Behavioral changes in the CR group were supported by fMRI data for a subset of participants. CONCLUSIONS:: The findings support the clinical efficacy of CR in early-stage AD. CR offers a means of assisting people with early-stage AD and their families in managing the effects of the condition.

OBJECTIVE:: To examine the utility of single-photon emission computed tomography (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). DESIGN:: Longitudinal, prospective study. SETTING:: University-based memory disorders clinic. PARTICIPANTS:: One hundred twenty seven patients with MCI and 59 healthy comparison subjects followed up for 1-9 years. MEASUREMENTS:: Diagnostic evaluation, neuropsychological tests, social/cognitive function, olfactory identification, apolipoprotein E genotype, magnetic resonance imaging, and brain Tc hexamethyl-propylene-aminoxime SPECT scan with visual ratings, and region of interest (ROI) analyses were done. RESULTS:: Visual ratings of SPECT temporal and parietal blood flow did not distinguish eventual MCI converters to AD (N = 31) from nonconverters (N = 96), but the global rating predicted conversion (41.9% sensitivity and 82.3% specificity, Fisher's exact test p = 0.013). Blood flow in each ROI was not predictive, but when dichotomized at the median value of the patients with MCI, low flow increased the hazard of conversion to AD for parietal (hazard ratio: 2.96, 95% confidence interval: 1.16-7.53, p = 0.023) and medial temporal regions (hazard ratio: 3.12, 95% confidence interval: 1.14-8.56, p = 0.027). In the 3-year follow-up sample, low parietal (p <0.05) and medial temporal (p <0.01) flow predicted conversion to AD, with or without controlling for age, Mini-Mental State Examination, and apolipoprotein E epsilon4 genotype. These measures lost significance when other strong predictors were included in logistic regression analyses: verbal memory, social/cognitive functioning, olfactory identification deficits, hippocampal, and entorhinal cortex volumes. CONCLUSIONS:: SPECT visual ratings showed limited utility in predicting MCI conversion to AD. The modest predictive utility of quantified low parietal and medial temporal flow using SPECT may decrease when other stronger predictors are available.

OBJECTIVES:: To examine the association between physical activity (PA) and Alzheimer disease (AD) course. BACKGROUND:: PA has been related to lower risk for AD. Whether PA is associated with subsequent AD course has not been investigated. METHODS:: In a population-based study of individuals aged 65 years and older in New York who were prospectively followed up with standard neurologic and neuropsychological evaluations (every approximately 1.5 years), 357 participants i) were nondemented at baseline and ii) were diagnosed with AD during follow-up (incident AD). PA (sum of participation in a variety of physical activities, weighted by the type of activity [light, moderate, and severe]) obtained 2.4 (standard deviation [SD], 1.9) years before incidence was the main predictor of mortality in Cox models and of cognitive decline in generalized estimating equation models that were adjusted for age, gender, ethnicity, education, comorbidities, and duration between PA evaluation and dementia onset. RESULTS:: One hundred fifty incident AD cases (54%) died during the course of 5.2 (SD, 4.4) years of follow-up. When compared with incident AD cases who were physically inactive, those with some PA had lower mortality risk, whereas incident AD participants with much PA had an even lower risk. Additional adjustments for apolipoprotein genotype, smoking, comorbidity index, and cognitive performance did not change the associations. PA did not affect rates of cognitive or functional decline. CONCLUSION:: Exercise may affect not only risk for AD but also subsequent disease duration: more PA is associated with prolonged survival in AD.

OBJECTIVES:: To test the hypothesis that cardiovascular risk factors (CRFs) influence predisposition to and the clinical course of Alzheimer disease (AD), the authors compared Choctaw Indians, a group with known high CRF with white persons with AD. In addition to CRF history, the authors investigated the frequency of apolipoprotein E4 (apoE4) genotype and plasma homocysteine (HC) levels. METHOD:: The authors compared 39 Choctaw Indians with AD and 39 Choctaw Indians without AD to 39 white persons with AD with all groups similar in age. CRF history included diabetes, hypertension, high cholesterol or hypolipidemic agent use, or myocardial infarction. The authors also compared plasma HC concentration and apoE4 allele frequency. RESULTS:: Choctaw persons with AD differed significantly from white persons with AD in history of hypertension, diabetes, and in HC values but not from Indians without AD. There was a significantly lower apoE4 allele frequency in Choctaw Indian AD than white persons with AD, and both AD groups had an affected first degree relative significantly more often than Indian controls. There was no relationship between the number of CRF and age at onset among Indians or whites, whereas HC concentration was associated with significantly earlier age of onset for Choctaw Indians but not for whites. CONCLUSIONS:: This small study suggests that in Choctaw Indians modifiable risk factors may play more of a role in disease pathogenesis than in whites and that nonmodifiable risk factors such as apoE4 may play less of a role.

OBJECTIVE:: The increased production of proinflammatory mediators such as cytokines and prostaglandins may interact at multiple levels with neurodegeneration in Alzheimer disease (AD). This study was undertaken to evaluate the possible role of interferon-gamma (IFN-gamma) T+874A, cytoplasmic phospholipase A2 (cPLA2) BanI, and cyclooxygenase-2 (COX-2) G-765C polymorphisms in AD. METHODS:: The study included 237 probable patients with AD who met the diagnostic criteria of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association, and 245 probands in the healthy comparison (HC) group. RESULTS:: No significant difference in mean age or in the distribution of genders between AD and HC groups was found. The COX-2 G/G genotype was significantly more frequent in the AD, when compared with the HC group. There was no significant correlation between IFN-gamma or cPLA2 genotypes and AD. CONCLUSIONS:: Our findings indicate that the COX-2 G/G genotype is associated with AD and support the involvement of COX-2 in AD etiology.

OBJECTIVES:: To investigate the associations between white matter (WM) integrity and cognitive reserve (CR) in healthy elders (HE), amnestic mild cognitive impairment (a-MCI), and Alzheimer disease (AD). The authors studied correlations between CR and WM integrity in regions showing WM age-related effects or pathologic changes and tested the differences of slopes between groups. METHODS:: Diffusion tensor images (DTIs) were obtained from 18 young individuals, 15 HE, 16 a-MCI cases, and 15 AD cases. Tract-based spatial statistics was used to process DTI data. Areas showing age-related fractional anisotropy (FA) shrinkages (HE < young) and pathology-related FA network "(AD < HE)" were defined. Correlations between CR and WM integrity were adjusted for age, gender, memory performance, and brain volumes. RESULTS:: HE presented more negative correlations between CR and WM integrity than patients with a-MCI and AD in age-related areas, such as the genum of the corpus callosum. However, these results were mediated by normal variability in memory function and brain volumes. For patients with a-MCI, negative associations between CR and FA were found in several major tracts, being more robust than in AD group. Although longitudinal results need to be interpreted with caution because of the reduced sample of patients with MCI, after 2 years of follow-up, all patients who progressed to AD had high-CR scores, suggesting a putative link between reduced WM integrity (maximal in patients with high CR) and risk of progression to AD. CONCLUSIONS:: CR correlates are implemented in different anatomic WM areas in HE and patients with a-MCI. Healthy elders with high CR may present better tolerance of typical age-related effects on WM integrity; in patients with a-MCI, the association may reflect increased capacity to cope with incipient cerebral damage.

OBJECTIVE:: Thisstudy aims to examine survival of patients with Alzheimer disease (AD) receiving clinical efficacy of cholinesterase inhibitors (ChEIs) and to compare their survival with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. DESIGN, SETTING, AND PARTICIPANTS:: The retrospective cohort study used national mortality data provided by the Korean National Statistics Office and electronic database of 15 general hospitals on older patients who began outpatient treatment with psychiatric medications including ChEIs (N = 3,813). The authors controlled for confounding by using multivariate models and propensity scoring methods. MEASUREMENTS:: Mortality rate of patients with AD receiving ChEIs was compared with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. RESULTS:: Observed additional survival of patients with AD receiving ChEIs (mortality rate: 13.1%), when compared with patients with AD who never received ChEIs (15.4%) was not statistically significant (p = 0.74; hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.67-1.59). Patients with AD receiving ChEIs showed higher mortality rate (13.1%) compared with that of cognitively intact old psychiatric outpatients (8.6%) (p <0.001; HR: 1.60, 95% CI: 0.96-2.68). CONCLUSION:: This study does not support that ChEIs increase survival of patients with AD, compared with patients with AD who have never treated with ChEIs. Therefore, all ChEIs should be considered for symptomatic use only and not to be capable of modifying mortality of patients with AD.

OBJECTIVE:: To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or mild cognitive impairment (MCI). DESIGN:: The authors examined cognitive function in a new analysis of an existing data set, the Cardiovascular Health Study, an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data. SETTING:: Community. PARTICIPANTS:: The authors examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow-up, and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 participants for the modified Mini-Mental State Examination (3MS) analysis and 350 participants for the digit symbol substitution test (DSST) analysis had sufficient follow-up data and apolipoprotein-epsilon (APOE) genotyping. MEASUREMENTS:: The 3MS and DSST were administered annually and analyzed using mixed-effects models including APOE4 status. RESULTS:: Mean 3MS and DSST scores did not differ between AD with psychosis (AD + P) and without psychosis groups at baseline. The 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis. CONCLUSIONS:: Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD + P may exert their effects by acceleration of the neurodegenerative process.

OBJECTIVES:: Alzheimer disease (AD) imposes a severe burden on patients and their caregivers. Although there is substantial evidence of the adverse impact of burden, considerably less is known about its specific correlates and potential causes. DESIGN:: The authors use data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-AD study to examine the relationship of burden and depression among AD caregivers to patient and caregiver sociodemographic characteristics, patients' cognitive status, psychiatric and behavioral symptoms, functional abilities, quality of life, and intensity of care provided by caregivers. SETTING:: CATIE-AD included outpatients in usual care settings and assessed treatment outcomes during 9 months. PARTICIPANTS:: Data were examined from 421 ambulatory outpatients with a diagnosis of dementia of the Alzheimer type or probable AD with agitation or psychosis. Measures: The Burden Interview, the Beck Depression Inventory, and the Caregiver Distress Scale were used to evaluate caregiver burden. RESULTS:: More severe psychiatric and behavioral problems and decreased patient quality of life, as well as lower functional capability were significantly associated with higher levels of burden and depression among caregivers at baseline. Six-month changes showed that decreased symptoms and improved quality of life were associated with decreased burden and accounted for most of the explained variance in change in burden measures. CONCLUSION:: Severity of psychiatric symptoms, behavioral disturbances, and patients' quality of life are the main correlates of caregivers' experience burden. Psychosocial and pharmacologic interventions targeting these two aspects of the disorder are likely to not only alleviate patient suffering but also promote caregiver well-being.

OBJECTIVES:: Depression in the elderly might represent a prodromal phase of Alzheimer disease (AD). High levels of plasma amyloid beta-42 (Abeta42) were found in prestages of AD and also in depressed patients in cross-sectional studies. This study examined the association of emerging late-onset depression (LOD) and AD with plasma Abeta42 in a sample of never depressed and not demented persons at baseline. DESIGN:: Prospective 5-year longitudinal study. PARTICIPANTS:: A community dwelling of older adults (N = 331) from the Vienna Transdanube Aging study. MEASUREMENTS:: Laboratory measurements, cognitive functioning, and depressive symptoms were assessed at baseline, 2.5, and 5 years follow-ups. RESULTS:: After exclusion of converters to AD, regression analysis revealed that higher plasma Abeta42 at baseline was a positive predictor for conversion to first episode of LOD. Independent of whether persons with mild cognitive impairment (MCI) at 2.5 years were included or excluded into regressions, higher plasma Abeta42 at baseline was a significant predictor for the development of probable or possible AD at 5 years. Higher conversion to AD was also associated with male gender but not with either higher scores on the Geriatric Depression Scale (GDS), with stroke or cerebral infarction nor apolipoprotein E epsilon4 allele. No association was found for an interaction between plasma Abeta42 levels and GDS. CONCLUSIONS:: Higher plasma Abeta42 at baseline predicted the development of first episode of LOD and conversion to probable or possible AD. Emerging depression as measured by scores on GDS at the 2.5-year follow-up, either alone or as an interaction factor with plasma Abeta42, failed to predict the conversion to AD at 5 years.

OBJECTIVES:: Early and progressive cognitive impairments of patients with Alzheimer disease (AD) hinder their capacity to provide informed consent. Unfortunately, the limited research on techniques to improve capacity has shown mixed results. Therefore, the authors tested whether a memory and organizational aid improves the performance of patients with AD on measures of capacity and competency to give informed consent. DESIGN, SETTING, AND PARTICIPANTS:: Patients with AD randomly assigned to standard consent or standard plus a memory and organizational aid. INTERVENTION:: Memory and organizational aid summarized the content of information mandated under the informed consent disclosure requirements of the Common Rule at a sixth grade reading level. MEASUREMENTS:: Three psychiatrists without access to patient data independently reviewed MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) interview transcripts to judge whether the patient was capable of providing informed consent. The agreement of at least two of the three experts defined a participant as capable of providing informed consent. Secondary outcomes are MacCAT-CR measures of understanding, appreciation and reasoning, and comparison with cognitively normal older adult norms. RESULTS:: AD intervention and control groups were similar in terms of age, education, and cognitive status. The intervention group was more likely to be judged competent than control group and had higher scores on MacCAT-CR measure of understanding. The intervention had no effect on the measures of appreciation or reasoning. CONCLUSIONS:: A consent process that addresses the deficits in memory and attention of a patient with AD can improve capacity to give informed consent for early phase AD research. The results also validate the MacCAT-CR as an instrument to measure capacity, especially the understanding subscale. TRIAL REGISTRY:: ClinicalTrials.Gov #NCT00105612, http://clinicaltrials.gov/show/NCT00105612.