Comparative study of machine learning methods for modeling associations between risk factors and future dementia cases.

A substantial portion of dementia risk can be attributed to modifiable risk factors that can be affected by lifestyle changes. Identifying the contributors to dementia risk could prove valuable. Recently, machine learning methods have been increasingly applied to healthcare data. Several studies have attempted to predict dementia progression by using such techniques. This study aimed to compare the performance of different machine-learning methods in modeling associations between known cognitive risk factors and future dementia cases. A subset of the AGES-Reykjavik Study dataset was analyzed using three machine-learning methods: logistic regression, random forest, and neural networks. Data were collected twice, approximately five years apart. The dataset included information from 1,491 older adults who underwent a cognitive screening process and were considered to have healthy cognition at baseline. Cognitive risk factors included in the models were based on demographics, MRI data, and other health-related data. At follow-up, participants were re-evaluated for dementia using the same cognitive screening process. Various performance metrics for all three machine learning algorithms were assessed. The study results indicate that a random forest algorithm performed better than neural networks and logistic regression in predicting the association between cognitive risk factors and dementia. Compared to more traditional statistical analyses, machine-learning methods have the potential to provide more accurate predictions about which individuals are more likely to develop dementia than others.

Exposure factors associated with dementia among older adults in Iceland: the AGES-Reykjavik study.

The study aimed to assess whether factors related to cognitive performance were associated with the development of dementia. Additionally, the study aimed to establish whether cognitive performance at baseline or change in cognition between baseline and follow-up (five-year period) had a stronger association with whether an individual would fulfill a dementia criterion at follow-up. The data was collected from 2002 to 2011. Logistic regression was applied to the AGES-Reykjavik Study epidemiological data. The analysis, which builds upon previous data analyses of the same dataset, included 1,491 participants between the ages of 66 and 90. All those included were considered to have normal cognition at baseline; 8.2% (n = 123) of them fulfilled a dementia criterion at follow-up five years later. The study's results indicated that being high on cognitive reserve factors reduced the risk of developing dementia. Compared to other known dementia risk factors, cognitive reserve factors (education level, participation in leisure activities, and self-reported health) were more likely than others to have an association with dementia. Additionally, the study's findings showed that cognitive performance at baseline, rather than change in cognition between baseline and follow-up five years later, had a stronger association with dementia at the follow-up assessment. Together, these findings support the notion that promoting high cognitive reserve throughout the lifespan and reaching high cognitive performance is important in reducing dementia risk.

The ambivalence toward neuropsychology in dementia research, diagnosis, and drug development: Myths and misconceptions.

Clinical assessment remains the gold standard for diagnosing dementia, monitoring progression, and conducting clinical research. Biomarkers hold promise for targeted therapeutic approaches, selection of participants in clinical trials, and direct physiological efficacy readouts. However, the anchoring of biomarker research to clinical symptomatology is often based on short and insensitive cognitive screening. This gives the impression that cognitive symptoms occur relatively late and that their progression in the early stages of the disease is slow. A thorough cognitive assessment is a powerful tool and has a key role in the accurate and early diagnosis of dementia. It is very different from the cognitive testing usually seen in biomarker research and drug development. Yet the distinction between these approaches is unclear to many. This paper highlights the misconceptions around cognitive research in dementia and suggests a way forward to facilitate biomarker and drug development through the improved utility of cognitive assessment tools.

Screening for possible hypopituitarism following mild traumatic brain injury: The first all-female study. Who do we need to evaluate further?

BACKGROUND: Studies on hypopituitarism (HP) following mild traumatic brain injury (mTBI) have focused on male populations although women may be more susceptible to the sequelae of mTBI. This is, to the best of our knowledge, the first all-female study screening for HP following mTBI. OBJECTIVE: Screening for possible HP in female athletes reporting a history of one or more mTBI. METHODS: Pituitary hormone screening blood tests (SBT) were performed in 133 of the 151 female athletes included. Repeated results outside the reference value (O-RV) were considered abnormal necessitating further endocrinological evaluation. RESULTS: Repeated SBT were O-RV in 88 women (66.2%). Decreased levels of serum insulin growth factor 1 (S-IGF1) were found in 55.6% of participants and elevated levels of serum prolactin (S-prolactin) in 22.6%. Serum cortisol levels were below the RV in 6.0% and thyroid hormonal levels in 11.3%. Lower age and increased number of mTBI symptoms correlated significantly with the risk of hormonal results O-RV. CONCLUSION: The majority of the study population had SBT O-RV, warranting further workup of possible HP. Decreased levels of S-IGF1 were most commonly observed followed by elevated S-prolactin possibly indicating hypothalamic-pituitary impairment. Lower age and increased number of symptoms of mTBI may indicate the need to screen for HP.

Lay Knowledge About Dementia in Iceland: Symptoms and Risk and Protective Factors.

No studies are available on the lay knowledge about dementia in Nordic countries. A survey was sent to 829 Icelanders aged 25 to 65 (61.2% female). 60.8% resided in the capital area of Reykjavik. About 90% or more recognized eight of eleven dementia symptoms, with females recognizing them proportionally more often than males. About 50% believed that an individual's risk of developing dementia could be modified. For individual risk factors, agreement ranged from 4% (hearing loss) to 75.1% (history of brain injury). Knowledge about cardiovascular risk factors ranged from 24.8% (obese) to 43.6% (high blood pressure). Participants acknowledged the importance of a healthy diet and an active lifestyle, but only 8% identified a low education level as a risk factor. Public health campaigns and educational efforts about dementia should focus on the whole lifespan targeting all risk and protective factors operating throughout the lifespan.

Cognition and brain health among older adults in Iceland: the AGES-Reykjavik study.

The paper aimed to compare how factors previously identified as predictive factors for cognitive decline and dementia related to cognitive performance on the one hand and brain health on the other. To that aim, multiple linear regression was applied to the AGES-Reykjavik study epidemiological data. Additionally, a regression analysis was performed for change in cognition over 5 years, using the same exposure factors. The study ran from 2002 to 2011, and the sample analyzed included 1707 participants between the ages of 66 and 90. The data contains MR imaging, cognitive testing, background data, and physiological measurements. Overall, we conclude that risk factors linked to dementia relate differently to cognition and brain health. Mobility, physical strength, alcohol consumption, coronary artery disease, and hypertension were associated with cognition and brain volume. Smoking, depression, diabetes, and body fat percentage were only associated with brain volume, not cognitive performance. Modifiable factors previously linked to cognitive reserve, such as educational attainment, participation in leisure activities, multilingualism and good self-reported health, were associated with cognitive function but did not relate to brain volume. These findings show that, within the same participant pool, cognitive reserve proxy variables have a relationship with cognitive performance but have no association with relative brain volume measured simultaneously.

Phenotypic Displays of Cholinergic Enzymes Associate With Markers of Inflammation, Neurofibrillary Tangles, and Neurodegeneration in Pre- and Early Symptomatic Dementia Subjects.

Background: Cholinergic drugs are the most commonly used drugs for the treatment of Alzheimer's disease (AD). Therefore, a better understanding of the cholinergic system and its relation to both AD-related biomarkers and cognitive functions is of high importance. Objectives: To evaluate the relationships of cerebrospinal fluid (CSF) cholinergic enzymes with markers of amyloidosis, neurodegeneration, neurofibrillary tangles, inflammation and performance on verbal episodic memory in a memory clinic cohort. Methods: In this cross-sectional study, 46 cholinergic drug-free subjects (median age = 71, 54% female, median MMSE = 28) were recruited from an Icelandic memory clinic cohort targeting early stages of cognitive impairment. Enzyme activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was measured in CSF as well as levels of amyloid-ß1-42 (Aß42), phosphorylated tau (P-tau), total-tau (T-tau), neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B), and glial fibrillary acidic protein (GFAP). Verbal episodic memory was assessed with the Rey Auditory Verbal Learning (RAVLT) and Story tests. Results: No significant relationships were found between CSF Aß42 levels and AChE or BuChE activity (p > 0.05). In contrast, T-tau (r = 0.46, p = 0.001) and P-tau (r = 0.45, p = 0.002) levels correlated significantly with AChE activity. Although neurodegeneration markers T-tau and NFL did correlate with each other (r = 0.59, p < 0.001), NFL did not correlate with AChE (r = 0.25, p = 0.09) or BuChE (r = 0.27, p = 0.06). Inflammation markers S100B and YKL-40 both correlated significantly with AChE (S100B: r = 0.43, p = 0.003; YKL-40: r = 0.32, p = 0.03) and BuChE (S100B: r = 0.47, p < 0.001; YKL-40: r = 0.38, p = 0.009) activity. A weak correlation was detected between AChE activity and the composite score reflecting verbal episodic memory (r = -0.34, p = 0.02). LASSO regression analyses with a stability approach were performed for the selection of a set of measures best predicting cholinergic activity and verbal episodic memory score. S100B was the predictor with the highest model selection frequency for both AChE (68%) and BuChE (73%) activity. Age (91%) was the most reliable predictor for verbal episodic memory, with selection frequency of both cholinergic enzymes below 10%. Conclusions: Results indicate a relationship between higher activity of the ACh-degrading cholinergic enzymes with increased neurodegeneration, neurofibrillary tangles and inflammation in the stages of pre- and early symptomatic dementia, independent of CSF Aß42 levels.

Towards defining biomarkers to evaluate concussions using virtual reality and a moving platform (BioVRSea).

Current diagnosis of concussion relies on self-reported symptoms and medical records rather than objective biomarkers. This work uses a novel measurement setup called BioVRSea to quantify concussion status. The paradigm is based on brain and muscle signals (EEG, EMG), heart rate and center of pressure (CoP) measurements during a postural control task triggered by a moving platform and a virtual reality environment. Measurements were performed on 54 professional athletes who self-reported their history of concussion or non-concussion. Both groups completed a concussion symptom scale (SCAT5) before the measurement. We analyzed biosignals and CoP parameters before and after the platform movements, to compare the net response of individual postural control. The results showed that BioVRSea discriminated between the concussion and non-concussion groups. Particularly, EEG power spectral density in delta and theta bands showed significant changes in the concussion group and right soleus median frequency from the EMG signal differentiated concussed individuals with balance problems from the other groups. Anterior-posterior CoP frequency-based parameters discriminated concussed individuals with balance problems. Finally, we used machine learning to classify concussion and non-concussion, demonstrating that combining SCAT5 and BioVRSea parameters gives an accuracy up to 95.5%. This study is a step towards quantitative assessment of concussion.

Core Competencies in Clinical Neuropsychology as a Training Model in Europe.

The multitude of training models and curricula for the specialty of clinical neuropsychology around the world has led to organized activities to develop a framework of core competencies to ensure sufficient expertise among entry-level professionals in the field. The Standing Committee on Clinical Neuropsychology of the European Federation of Psychologists' Associations is currently working toward developing a specialty certification in clinical neuropsychology to establish a cross-national standard against which to measure levels of equivalency and uniformity in competence and service provision among professionals in the field. Through structured interviews with experts from 28 European countries, we explored potential areas of core competency. Specifically, questions pertained to the perceived importance of a series of foundational, functional, and other competencies, as well as current training standards and practices, and optimal standards. Our findings revealed considerable agreement (about three quarters and above) on academic and clinical training, despite varied actual training requirements currently, with fewer respondents relegating importance to training in teaching, supervision, and research (a little over half), and even fewer to skills related to management, administration, and advocacy (fewer than half). European expert clinical neuropsychologists were in agreement with previous studies (including those conducted in the United States, Australia, and other countries) regarding the importance of sound theoretical and clinical training but management, administrative, and advocacy skills were not central to their perspective of a competent specialist in clinical neuropsychology. Establishing a specialty certificate in clinical neuropsychology based on core competencies may enable mobility of clinical neuropsychologists across Europe, and, perhaps, provide an impetus for countries with limited criteria to reconsider their training requirements and harmonize their standards with others.

Creativity, leisure activities, social engagement and cognitive impairment: the AGES-Reykjavík study.

BACKGROUND: Participation in leisure activities and extensive social network have been associated with lower risk of cognitive impairment (CI) and dementia. AIMS: We examined whether leisure activities (cognitive solitary, cognitive group, social, physical, or creative activities) and social involvement are associated with less incidence of CI or dementia. METHODS: Analyses were performed from data of 2933 cognitively intact individuals at baseline included in the AGES-REYKJAVIK study. Odds ratios (OR) were calculated for incident CI and dementia in relation to cognitive individual, cognitive group, social, physical, and creative leisure activities as well as social networks. Models were adjusted for a number of known risk factors for cognitive decline. RESULTS: In 5 years, 12% of the cohort were diagnosed with CI or dementia. All leisure activities were associated with reduced likelihood of cognitive decline in the raw model, but in adjusted models, cognitive solitary [OR 0.49 (Confidence Interval (CI) 0.38-0.64)], cognitive group [OR 0.50 (CI 0.30-0.82)], and creative activities [OR 0.53 (CI 0.35-0.83)] were significantly associated with less cognitive decline. Analyses examining creative leisure activities independently, controlling for all other activities, suggested individuals participating in creative activities exhibited less CI [OR 0.64 (CI 0.41-0.98)]. Among social networks variables, frequency of meeting with friends and relatives was associated with reduced likelihood of CI [OR 0.49 (CI 0.31-0.75)]. DISCUSSION: Cognitive and creative leisure activities and frequent gatherings with friends and relatives are associated with reduced incidence of CI in this older cohort. CONCLUSION: Creative leisure activities might have special benefit for cognitive ability.

European Clinical Neuropsychology: Role in Healthcare and Access to Neuropsychological Services.

This study analyzed aspects of the work of clinical neuropsychologists across Europe. There are no published comparisons between European countries regarding the nature of clinical neuropsychologists' work. Forty-one national psychological and neuropsychological societies were approached, of which 31 (76%) responded. Data from seven countries with less than 10 neuropsychologists were excluded. A license is required to practice clinical neuropsychology in 50% of the countries. Clinical neuropsychologists work independently in 62.5%. Diagnostic/assessment work is the most frequently reported activity (54%). Most neuropsychologists work in public hospitals, followed by health centers. Adult neuropsychology was the most frequent area of activity. Services in public institutions are covered by public entities (45.8%), or by a combination of patient funds and public entities (29.2%) and only 4.2% by the patient; whereas services in private institutions are covered by the patient (26.1%) and the combination of patient, public entities (21.7%) or patient and private entities (17.4%). The data suggest that the number of neuropsychologists working across European countries is considerably low in comparison to other medical professionals. The results of the survey identified similar aspects of neuropsychologists' work, despite variations in terms of reimbursement and mechanisms, reflecting economic and healthcare differences. Estimates on the number of clinical neuropsychologists suggest insufficient access to neuropsychological services.

Cerebrospinal Fluid C18 Ceramide Associates with Markers of Alzheimer's Disease and Inflammation at the Pre- and Early Stages of Dementia.

BACKGROUND: Understanding how dysregulation in lipid metabolism relates to the severity of Alzheimer's disease (AD) pathology might be critical in developing effective treatments. OBJECTIVE: To identify lipid species in cerebrospinal fluid (CSF) associated with signature AD pathology and to explore their relationships with measures reflecting AD-related processes (neurodegeneration, inflammation, deficits in verbal episodic memory) among subjects at the pre- and early symptomatic stages of dementia. METHODS: A total of 60 subjects that had been referred to an Icelandic memory clinic cohort were classified as having CSF AD (n = 34) or non-AD (n = 26) pathology profiles. Untargeted CSF lipidomic analysis was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) for the detection of mass-to-charge ratio (m/z) features. CSF proteins reflecting neurodegeneration (neurofilament light [NFL]) and inflammation (chitinase-3-like protein 1 [YKL-40], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein [GFAP]) were also measured. Rey Auditory Verbal Learning (RAVLT) and Story tests were used for the assessment of verbal episodic memory. RESULTS: Eight out of 1008 features were identified as best distinguishing between the CSF profile groups. Of those, only the annotation of the m/z feature assigned to lipid species C18 ceramide was confirmed with a high confidence. Multiple regression analyses, adjusted for age, gender, and education, demonstrated significant associations of CSF core AD markers (Aß42: st.ß= -0.36, p = 0.007; T-tau: st.ß= 0.41, p = 0.005) and inflammatory marker S100B (st.ß= 0.51, p = 0.001) with C18 ceramide levels. CONCLUSION: Higher levels of C18 ceramide associated with increased AD pathology and inflammation, suggesting its potential value as a therapeutic target.

Body weight changes and longitudinal associations with cognitive decline among community-dwelling older adults.

INTRODUCTION: We aim to investigate the longitudinal associations between changes in body weight (BW) and declines in cognitive function and risk of mild cognitive impairment (MCI)/dementia among cognitively normal individuals 65 years or older. METHODS: Data from the Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) including 2620 participants, were examined using multiple logistic regression models. Cognitive function included speed of processing (SP), executive function (EF), and memory function (MF). Changes in BW were classified as; weight loss (WL), weight gain (WG), and stable weight (SW). RESULTS: Mean follow-up time was 5.2 years and 61.3% were stable weight. Participants who experienced WL (13.4%) were significantly more likely to have declines in MF and SP compared to the SW group. Weight changes were not associated with EF. WL was associated with a higher risk of MCI, while WG (25.3%) was associated with a higher dementia risk, when compared to SW. DISCUSSION: Significant BW changes in older adulthood may indicate impending changes in cognitive function.

Self-reported concussion history among Icelandic female athletes with and without a definition of concussion.

OBJECTIVE: This study examined whether Icelandic female athletes in contact sports, based their self-reported concussion history on adequate medical definitions, by assessing self-reported concussion history with and without a definition of concussion. Another aim was to examine whether currently active athletes were more knowledgeable of concussions than retired athletes. METHODS: Participants (age = 26.9, SD = 7.1) were 508 former (34.5%) and current (65.5%) elite female athletes in soccer (41%), handball (30.6%), basketball (19.1%), ice hockey (4.5%) and combat sports (4.7%). An online questionnaire (QuestionPro) was distributed to females in contact sports (snowball sampling). Participants later came for an in-person interview where the authenticity of previous responses was confirmed. In the questionnaire, participants answered background questions and questions about concussion history. First, they reported the total number of sustained concussions without a prompt. They reported the number of sustained concussions again after reading a definition of concussion. Participants could not correct their previous answers. Pearson's Chi-square was used for group comparisons. RESULTS: The prevalence of reported concussions increased from 40.2% to 64.8% following a definition. There was no significant difference in how many participants changed their answer when asked about sustaining SRCs before and after reading the definition based on whether the participants were still competitive or retired X2(1) = 0.69, p = 0.41. CONCLUSIONS: Our data suggest that understanding of concussions is inadequate among female athletes. Self-report will continue to be an essential source of clinical information and prompting with a definition can increase the reliability of self-reported concussions.

Association of glial and neuronal degeneration markers with Alzheimer's disease cerebrospinal fluid profile and cognitive functions.

BACKGROUND: Neuroinflammation has gained increasing attention as a potential contributing factor in the onset and progression of Alzheimer's disease (AD). The objective of this study was to examine the association of selected cerebrospinal fluid (CSF) inflammatory and neuronal degeneration markers with signature CSF AD profile and cognitive functions among subjects at the symptomatic pre- and early dementia stages. METHODS: In this cross-sectional study, 52 subjects were selected from an Icelandic memory clinic cohort. Subjects were classified as having AD (n = 28, age = 70, 39% female, Mini-Mental State Examination [MMSE] = 27) or non-AD (n = 24, age = 67, 33% female, MMSE = 28) profile based on the ratio between CSF total-tau (T-tau) and amyloid-ß1-42 (Aß42) values (cut-off point chosen as 0.52). Novel CSF biomarkers included neurofilament light (NFL), YKL-40, S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP), measured with enzyme-linked immunosorbent assays (ELISAs). Subjects underwent neuropsychological assessment for evaluation of different cognitive domains, including verbal episodic memory, non-verbal episodic memory, language, processing speed, and executive functions. RESULTS: Accuracy coefficient for distinguishing between the two CSF profiles was calculated for each CSF marker and test. Novel CSF markers performed poorly (area under curve [AUC] coefficients ranging from 0.61 to 0.64) compared to tests reflecting verbal episodic memory, which all performed fair (AUC > 70). LASSO regression with a stability approach was applied for the selection of CSF markers and demographic variables predicting performance on each cognitive domain, both among all subjects and only those with a CSF AD profile. Relationships between CSF markers and cognitive domains, where the CSF marker reached stability selection criteria of > 75%, were visualized with scatter plots. Before calculations of corresponding Pearson's correlations coefficients, composite scores for cognitive domains were adjusted for age and education. GFAP correlated with executive functions (r = - 0.37, p = 0.01) overall, while GFAP correlated with processing speed (r = - 0.68, p < 0.001) and NFL with verbal episodic memory (r = - 0.43, p = 0.02) among subjects with a CSF AD profile. CONCLUSIONS: The novel CSF markers NFL and GFAP show potential as markers for cognitive decline among individuals with core AD pathology at the symptomatic pre- and early stages of dementia.

Incidence of Brain Infarcts, Cognitive Change, and Risk of Dementia in the General Population: The AGES-Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study).

BACKGROUND AND PURPOSE: The differentiation of brain infarcts by region is important because their cause and clinical implications may differ. Information on the incidence of these lesions and association with cognition and dementia from longitudinal population studies is scarce. We investigated the incidence of infarcts in cortical, subcortical, cerebellar, and overall brain regions and how prevalent and incident infarcts associate with cognitive change and incident dementia. METHODS: Participants (n=2612, 41% men, mean age 74.6±4.8) underwent brain magnetic resonance imaging for the assessment of infarcts and cognitive testing at baseline and on average 5.2 years later. Incident dementia was assessed according to the international guidelines. RESULTS: Twenty-one percent of the study participants developed new infarcts. The risk of incident infarcts in men was higher than the risk in women (1.8; 95% confidence interval, 1.5-2.3). Persons with both incident and prevalent infarcts showed steeper cognitive decline and had almost double relative risk of incident dementia (1.7; 95% confidence interval, 1.3-2.2) compared with those without infarcts. Persons with new subcortical infarcts had the highest risk of incident dementia compared with those without infarcts (2.6; 95% confidence interval, 1.9-3.4). CONCLUSIONS: Men are at greater risk of developing incident brain infarcts than women. Persons with incident brain infarcts decline faster in cognition and have an increased risk of dementia compared with those free of infarcts. Incident subcortical infarcts contribute more than cortical and cerebellar infarcts to incident dementia which may indicate that infarcts of small vessel disease origin contribute more to the development of dementia than infarcts of embolic origin in larger vessels.

Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.

BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. METHODS: We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults. RESULTS: rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism. CONCLUSIONS: This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.

The alcohol paradox: light-to-moderate alcohol consumption, cognitive function, and brain volume.

BACKGROUND: Studies of older persons show consumption of light-to-moderate amounts of alcohol is positively associated with cognitive function and, separately, is negatively associated with total brain volume (TBV). This is paradoxical as generally, cognitive function is positively associated with TBV. We examined the relationships of TBV, global cognitive function (GCF), and alcohol consumption in a population-based cohort of 3,363 men and women (b. 1907-1935) participating in the Age Gene/Environment Susceptibility-Reykjavik Study (2002-2006) and who were free of dementia or mild cognitive impairment METHODS: Drinking status (never, former, and current) and current amount of alcohol consumed were assessed by questionnaire. GCF is a composite score derived from a battery of cognitive tests. TBV, standardized to head size, is estimated quantitatively from brain magnetic resonance imaging. RESULTS: Among women and not men, adjusting for demographic and cardiovascular risk factors, current drinkers had significantly higher GCF scores than abstainers and former drinkers (p < .0001); and GCF was associated with amount consumed. TBV was not associated with drinking status or amount consumed in men or women. GCF and TBV did significantly differ in their associations across alcohol categories (p interaction < .001). Within categories of alcohol intake, GCF and TBV were positively associated. CONCLUSIONS: The difference in associations of alcohol intake to brain structure and function suggests there may be unmeasured factors that contribute to maintaining better GCF relative to TBV. However, at higher levels of reasonable alcohol consumption, there may be factors leading to reduced brain volume.

Spousal loss and cognitive function in later life: a 25-year follow-up in the AGES-Reykjavik study.

The aim of this study was to investigate the associations between loss of a life partner and the development of dementia and decline in cognitive function in later life. We used an Icelandic cohort of 4,370 participants in the Age, Gene/Environment Susceptibility-Reykjavik Study who were living as married in 1978 (born in 1907-1935) and were either still married (unexposed cohort) or widowed (exposed cohort) at follow-up (in 2002-2006). We ascertained history of marital status and spouse's death by record linkage to the Registry of the Total Population, Statistics Iceland. The outcome measures were as follows: 1) dementia and mild cognitive impairment; and 2) memory, speed of processing, and executive function. During the observation period, 3,007 individuals remained married and 1,363 lost a spouse through death. We did not find any significant associations between loss of a spouse and our outcome variables, except that widowed women had poorer executive function (mean = -0.08) during the first 2 years after their husbands' deaths compared with still-married women (mean = 0.09). Our findings do not support the notion that the risk of dementia is increased following the loss of a spouse, yet women demonstrate a seemingly temporary decline in executive function following the death of a partner.