Subjective word-finding difficulty reduces engagement in social leisure activities in Alzheimer's disease.

Objectives: To assess the influence of subjective word-finding difficulty on degree of engagement in social leisure activities among individuals with Alzheimer's disease (AD).

Design: Analysis of data collected from the second cohort of the Multicenter Study of Predictors of Disease Course in Alzheimer's disease.

Setting: Four study sites in the United States and France.

Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria.

In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology.

Unilateral disruptions in the default network with aging in native space.

Background: Disruption of the default-mode network (DMN) in healthy elders has been reported in many studies.

Methods: In a group of 51 participants (25 young, 26 elder) we examined DMN connectivity in subjects' native space. In the native space method, subject-specific regional masks (obtained independently for each subject) are used to extract regional fMRI times series.

Neuroimaging explanations of age-related differences in task performance.

Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships.

Social cognition in Alzheimer's disease: a separate construct contributing to dependence.

The extent to which social cognitive changes reflect a discrete constellation of symptoms dissociable from general cognitive changes in Alzheimer's disease (AD) is unclear. Moreover, whether social cognitive symptoms contribute to disease severity and progression is unknown. The current multicenter study investigated cross-sectional and longitudinal associations between social cognition measured with six items from the Blessed Dementia Rating Scale, general cognition, and dependence in 517 participants with probable AD.

Health-care use and cost in dementia caregivers: Longitudinal results from the Predictors Caregiver Study.

Objective: To examine the effects of caregiver and patient characteristics on caregivers' medical care use and cost.

Methods: One hundred forty-seven caregiver/patient dyads were followed annually for 6 years in three academic Alzheimer's disease centers in the United States. Logistic, negative binomial, and generalized linear mixed models were used to examine overall effects of caregiver/patient characteristics on caregivers' hospitalizations, doctor visits, outpatient tests and procedures, and prescription and over-the-counter medications.

The role of education and verbal abilities in altering the effect of age-related gray matter differences on cognition.

Evidence suggests that individual variability in lifetime exposures influences how cognitive performance changes with advancing age. Brain maintenance and cognitive reserve are theories meant to account for preserved performance despite advancing age. These theories differ in their causal mechanisms.

Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up.

Reliability, validity, and interpretation of the dependence scale in mild to moderately severe Alzheimer's disease.

Introduction: The Dependence Scale (DS) was designed to measure dependence on others among patients with Alzheimer's disease (AD). The objectives of this research were primarily to strengthen the psychometric evidence for the use of the DS in AD studies.

Methods: Patients with mild to moderately severe AD were examined in 3 study databases.

Characterizing the normative profile of 18F-FDG PET brain imaging: sex difference, aging effect, and cognitive reserve.

The aim of this study was to investigate findings of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG PET) in normal subjects to clarify the effects of sex differences, aging, and cognitive reserve on cerebral glucose metabolism. Participants comprised 123 normal adults who underwent 18F-FDG PET and a neuropsychological battery. We used statistical parametric mapping (SPM8) to investigate sex differences, and aging effects.

Promising developments in neuropsychological approaches for the detection of preclinical Alzheimer's disease: a selective review.

Recently published guidelines suggest that the most opportune time to treat individuals with Alzheimer's disease is during the preclinical phase of the disease. This is a phase when individuals are defined as clinically normal but exhibit evidence of amyloidosis, neurodegeneration and subtle cognitive/behavioral decline. While our standard cognitive tests are useful for detecting cognitive decline at the stage of mild cognitive impairment, they were not designed for detecting the subtle cognitive variations associated with this biomarker stage of preclinical Alzheimer's disease.

Change in body mass index before and after Alzheimer's disease onset.

Objectives: A high body mass index (BMI) in middle-age or a decrease in BMI at late-age has been considered a predictor for the development of Alzheimer's disease (AD). However, little is known about the BMI change close to or after AD onset.

Methods: BMI of participants from three cohorts, the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based), and National Alzheimer's Coordinating Center (NACC; clinic-based) were analyzed longitudinally.

The differential impact of unique behavioral and psychological symptoms for the dementia caregiver: how and why do patients' individual symptom clusters impact caregiver depressive symptoms?

Objective: The behavioral and psychological symptoms associated with dementia (BPSD) are highly burdensome to caregivers. While BPSD consist of a wide variety of patient behaviors including depression, physical aggression, and paranoid delusions, it remains unclear whether specific symptoms have a differential impact on caregivers. The aims of this study were 1) to assess how individual BPSD, categorized based on how they may affect caregivers, impact depressive symptoms for dementia patient caregivers and 2) to test the pathways by which BPSD clusters impact caregiver depressive symptoms.

COSMIC (Cohort Studies of Memory in an International Consortium): an international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups.

Background: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.

Bilingualism does not alter cognitive decline or dementia risk among Spanish-speaking immigrants.

Objective: Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared with monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially nondemented Hispanic immigrants living in a Spanish-speaking enclave of northern Manhattan.

Method: Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18-24 month intervals for up to 23 years.

Netrin-1 promotes excitatory synaptogenesis between cortical neurons by initiating synapse assembly.

Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain during the postnatal period of peak synapse formation. Here we demonstrate a synaptogenic function of netrin-1 in rat and mouse cortical neurons and investigate the underlying mechanism. We report that netrin-1 and its receptor DCC are widely expressed by neurons in the developing mammalian cortex during synapse formation and are enriched at synapses in vivo.

Functional status in the young-old: establishing a working prototype of an extended-instrumental activities of daily living scale.

Background: Instrumental activities of daily living (IADLs) exhibit strong predictive power for the presence of dementia and mild cognitive impairment. However, IADLs are often less effective in younger cohorts or in healthy community-dwelling samples, presenting with large ceiling effects. This study aimed to construct an IADL scale with an extended range.

Apolipoprotein E-ε4 polymorphism and cognitive dysfunction after carotid endarterectomy.

Approximately 25% of patients undergoing carotid endarterectomy (CEA) exhibit cognitive dysfunction (CD) 1 day and 1 month after CEA. The apolipoprotein E (apoE)-ε4 polymorphism has been previously identified as a robust independent risk factor for CD 1 month after CEA. We aimed to determine whether the apoE-ε4 polymorphism is also an independent risk factor for CD as early as 1 day after CEA and to confirm the previous findings at 1 month.

Resting state inter and intra hemispheric human brain functional connectivity.

Resting-state functional connectivity between neuroanatomical regions has attracted significant attention in recent years. In the process of obtaining the resting-state functional connectivity map of the human brain from blood-oxygen-level-dependent fMRI signals, it is common to average the signals from left and right hemispheres. This averaging can introduce unappreciated complexities and unintended consequences not related to the research question of interest.

A new algorithm for predicting time to disease endpoints in Alzheimer's disease patients.

Background: The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies.

Objective: To develop and validate a prediction algorithm that uses data from a single visit to estimate time to important disease endpoints for individual Alzheimer's disease patients.

Method: Two separate study cohorts (Predictors 1, N = 252; Predictors 2, N = 254), all initially with mild Alzheimer's disease, were followed for 10 years at three research centers with semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information.

Cognitive declines precede and predict functional declines in aging and Alzheimer's disease.

Objective: To investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer's disease (AD).

Design And Setting: A community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project) and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study).

Participants: 3,443 initially non-demented older adults (612 with eventual incident dementia) and 517 patients with AD.

Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve.

Cognitive reserve (CR) is a concept meant to account for the frequent discrepancy between an individual's measured level of brain pathology and her expected cognitive performance. It is particularly important within the context of aging and dementia, but has wider applicability to all forms of brain damage. As such, it has intimate links to related compensatory and neuroprotective concepts, as well as to the related notion of brain reserve.

Alcohol intake and brain structure in a multiethnic elderly cohort.

Background & Aims: Evidence suggests that consuming light-to-moderate amounts of alcohol reduces the risk of dementia and is associated better cognitive function and less cardiovascular disease, relative to those consuming no or heavy alcohol. There are only minimal data on the association between alcohol and brain magnetic resonance imaging (MRI) markers. This study aimed to examine the association between alcohol and brain structure measured with MRI.

Cognitive reserve: implications for assessment and intervention.

The concept of reserve is used to explain the observation that some individuals function better than others in the presence of brain pathology. This article reviews the concept of reserve from its theoretical basis to the implication of reserve for clinical practice. A distinction between brain reserve, referring to individual differences in the anatomic substrate, and cognitive reserve, referring to differences in the flexibility or adaptivity of cognitive networks, is useful.