Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations.

BACKGROUND: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research. OBJECTIVES: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer's disease (AD) using cohort studies. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model. RESULTS: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project. CONCLUSIONS: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings.

Medial temporal lobe functional connectivity predicts stimulation-induced theta power.

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5-8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended to decrease power in the high-frequency broadband (HFB; 50-200 Hz) range, and these modulations were correlated with HFB-based networks in a subset of subjects. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, capturing evoked activity across brain regions and frequency bands.

Rapidly developing multimorbidity and disability in older adults: does social background matter?

BACKGROUND: Multimorbidity is among the most disabling geriatric conditions. In this study, we explored whether a rapid development of multimorbidity potentiates its impact on the functional independence of older adults, and whether different sociodemographic factors play a role beyond the rate of chronic disease accumulation. METHODS: A random sample of persons aged ≥60 years (n = 2387) from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) was followed over 6 years. The speed of multimorbidity development was estimated as the rate of chronic disease accumulation (linear mixed models) and further dichotomized into the upper versus the three lower rate quartiles. Binomial negative mixed models were used to analyse the association between speed of multimorbidity development and disability (impaired basic and instrumental activities of daily living), expressed as the incidence rate ratio (IRR). The effect of sociodemographic factors, including sex, education, occupation and social network, was investigated. RESULTS: The risk of new activity impairment was higher among participants who developed multimorbidity faster (IRR 2.4, 95% CI 1.9-3.1) compared with those who accumulated diseases more slowly overtime, even after considering the baseline number of chronic conditions. Only female sex (IRR for women vs. men 1.6, 95% CI 1.2-2.0) and social network (IRR for poor vs. rich social network 1.7, 95% CI 1.3-2.2) showed an effect on disability beyond the rate of chronic disease accumulation. CONCLUSIONS: Rapidly developing multimorbidity is a negative prognostic factor for disability. However, sociodemographic factors such as sex and social network may determine older adults' reserves of functional ability, helping them to live independently despite the rapid accumulation of chronic conditions.

Widespread theta synchrony and high-frequency desynchronization underlies enhanced cognition.

The idea that synchronous neural activity underlies cognition has driven an extensive body of research in human and animal neuroscience. Yet, insufficient data on intracranial electrical connectivity has precluded a direct test of this hypothesis in a whole-brain setting. Through the lens of memory encoding and retrieval processes, we construct whole-brain connectivity maps of fast gamma (30-100 Hz) and slow theta (3-8 Hz) spectral neural activity, based on data from 294 neurosurgical patients fitted with indwelling electrodes. Here we report that gamma networks desynchronize and theta networks synchronize during encoding and retrieval. Furthermore, for nearly all brain regions we studied, gamma power rises as that region desynchronizes with gamma activity elsewhere in the brain, establishing gamma as a largely asynchronous phenomenon. The abundant phenomenon of theta synchrony is positively correlated with a brain region's gamma power, suggesting a predominant low-frequency mechanism for inter-regional communication.

Nutritional status and survival among old adults: an 11-year population-based longitudinal study.

BACKGROUND/OBJECTIVES: The impact of nutritional status on survival among community-dwelling older adults is unclear. We aimed to investigate the prevalence and association of poor nutritional status, including malnutrition and risk for malnutrition defined by the Mini-Nutritional Assessment-Short Form (MNA-SF) with survival, and to explore the role of relevant biomarkers (hemoglobin, albumin and C-reactive protein) in this association. SUBJECTS/METHODS: This study included 3041 participants aged ⩾ 60 in the Swedish National study on Aging and Care-Kungsholmen. On the basis of the total score in MNA-SF, nutritional status for each participant was assessed as normal (score 12-14), risk for malnutrition (8-11) or malnutrition (<8). Over an 11-year follow-up, survival status was observed. Data were analysed using logistic regression, flexible parametric survival and Laplace models. RESULTS: Of all the participants, 51 (1.7%) had malnutrition and 751 (24.7%) were at risk for malnutrition. The multi-adjusted hazard ratio (95% confidence interval) of mortality was 2.40 (1.56-3.67; P<0.001) for malnutrition and 1.49 (1.29-1.71; P<0.001) for risk for malnutrition. The median ages at death of participants with malnutrition and risk for malnutrition were ~3 and 1.5 years shorter than those with normal nutritional status, respectively, whereas malnutrition or risk for malnutrition together with abnormal biomarker (hemoglobin and albumin) levels was related to 1 year more shortened survival. CONCLUSIONS: Malnutrition and risk for malnutrition are highly prevalent and significantly associated with a shorter survival. Poor nutritional status in combination with abnormalities in the biomarkers is associated with even more shortened survival.

Lifestyle factors related to mortality and survival: a mini-review.

As the world's population ages, elderly people are becoming an increasingly important group that merits special attention with regard to health and social issues. Lifestyles affect health and survival at all ages, but the consequences of poor lifestyle behaviors may be different for elderly people than for younger adults. They can also be heavily dependent on exposure earlier in life. Our current state of knowledge is based predominantly on studies conducted among middle-aged adults or young elderly people. Moreover, studies are sparse throughout the entire older age spectrum, from 65 to 90 years. This article summarizes the evidence regarding the impact of lifestyle behaviors on mortality among elderly people. It focuses on behaviors modifiable by individual actions and public health interventions, such as smoking, obesity and sedentary behavior, which predispose numerous people to diseases that rank among the leading causes of death, including heart disease, cancer, stroke, diabetes and dementia. These factors not only shorten life but, when they occur together, also have a major impact on survival beyond that associated with each single lifestyle factor. We propose an integrated life course model to guide research on longevity to answer questions that remain open and to find new strategies to ensure a longer and healthier life for future generations.

The impact of chronic multimorbidity and disability on functional decline and survival in elderly persons. A community-based, longitudinal study.

OBJECTIVE: We aimed to disentangle the effect of chronic multimorbidity and disability on 3-year functional decline and survival in the elderly. DESIGN: Prospective cohort study with a mean of follow-up of 2.8 years. SETTING: Swedish elderly persons from the Kungsholmen Project (1987-2000). SUBJECTS: A total of 1099 subjects, 77-100 years old, living in the community and institutions. MAIN OUTCOME MEASUREMENTS: Medical diagnoses (based on clinical examination, drug use, medical records and blood tests), and functional assessment (according to Katz Index) at baseline were investigated in relation to functional decline and death occurring during follow-up. RESULTS: At baseline, 12.1% of participants had disability, and 52.3% were affected by multimorbidity. During follow-up, 363 persons died and 85 worsened in functioning. The number of chronic conditions incrementally increased the risk of functional decline [hazard ratio (HR) increased from 1.5 in subjects with one disease to 6.2 in persons with 4+ diseases]. However, this was not the case for mortality, as the HR of death was the same for people with one disease as well as 4+ diseases (HR=2.3). Baseline disability had the highest impact on survival, independently of number of diseases [HR=8.1; 95% confidence interval (CI)=4.8-13.7 in subjects with one disease and HR=7.7; 95% CI=4.7-12.6 in those with 2+ diseases]. CONCLUSIONS: In the elderly subjects, chronic disability rather than multimorbidity emerged as the strongest negative prognostic factor for functionality and survival.

Reset of human neocortical oscillations during a working memory task.

Both amplitude and phase of rhythmic slow-wave electroencephalographic activity are physiological correlates of learning and memory in rodents. In humans, oscillatory amplitude has been shown to correlate with memory; however, the role of oscillatory phase in human memory is unknown. We recorded intracranial electroencephalogram from human cortical and hippocampal areas while subjects performed a short-term recognition memory task. On each trial, a series of four list items was presented followed by a memory probe. We found agreement across trials of the phase of oscillations in the 7- to 16-Hz range after randomly timed stimulus events, evidence that these events either caused a phase shift in the underlying oscillation or initiated a new oscillation. Phase locking in this frequency range was not generally associated with increased poststimulus power, suggesting that stimulus events reset the phase of ongoing oscillations. Different stimulus classes selectively modulated this phase reset effect, with topographically distinct sets of recording sites exhibiting preferential reset to either probe items or to list items. These findings implicate the reset of brain oscillations in human working memory.

An autoassociative neural network model of paired-associate learning.

Hebbian heteroassociative learning is inherently asymmetric. Storing a forward association, from item A to item B, enables recall of B (given A), but does not permit recall of A (given B). Recurrent networks can solve this problem by associating A to B and B back to A. In these recurrent networks, the forward and backward associations can be differentially weighted to account for asymmetries in recall performance. In the special case of equal strength forward and backward weights, these recurrent networks can be modeled as a single autoassociative network where A and B are two parts of a single, stored pattern. We analyze a general, recurrent neural network model of associative memory and examine its ability to fit a rich set of experimental data on human associative learning. The model fits the data significantly better when the forward and backward storage strengths are highly correlated than when they are less correlated. This network-based analysis of associative learning supports the view that associations between symbolic elements are better conceptualized as a blending of two ideas into a single unit than as separately modifiable forward and backward associations linking representations in memory.

Gating of human theta oscillations by a working memory task.

Electrode grids on the cortical surface of epileptic patients provide a unique opportunity to observe brain activity with high temporal-spatial resolution and high signal-to-noise ratio during a cognitive task. Previous work showed that large-amplitude theta frequency oscillations occurred intermittently during a maze navigation task, but it was unclear whether theta related to the spatial or working memory components of the task. To determine whether theta occurs during a nonspatial task, we made recordings while subjects performed the Sternberg working memory task. Our results show event-related theta and reveal a new phenomenon, the cognitive "gating" of a brain oscillation: at many cortical sites, the amplitude of theta oscillations increased dramatically at the start of the trial, continued through all phases of the trial, including the delay period, and decreased sharply at the end. Gating could be seen in individual trials and varying the duration of the trial systematically varied the period of gating. These results suggest that theta oscillations could have an important role in organizing multi-item working memory.