Normative data and repeatability for macular ganglion cell layer thickness in healthy Swedish children using swept source optical coherence tomography.

BACKGROUND: Optical coherent tomography (OCT) technology is evolving with improved resolution and accuracy in segmentation between different cell layers in the retina. The ganglion cell layer in the macula region is a window to see what is happening in the visual pathways and a macula OCT is an examination that most children tolerate. This makes updated normative data necessary since variables may differ between different OCT devices and normative data for children is often not presented. The aim of this study was to develop normative data for macular ganglion cell layer thickness in children, measured with swept source OCT, and investigate the repeatability between measurements. METHODS: Healthy Swedish children between 4 and 16 years old, with normal refraction, spherical equivalent mean:1.13 (sd:0.66) dioptre and normal visual acuity Logmar, mean: 0,015 (sd:0,05), were examined with swept source OCT. Macula OCT was performed three times in both eyes and the different retinal layers were evaluated. RESULTS: Fifty-eight children were screened for inclusion. Fifty-five children were included in the study, 24 boys and 31 girls. Mean age was 8.9 years. Results from right eyes was analysed. The mean average thickness of macular ganglion cell layer thickness, retinal nerve fibre layer/ganglion cell layer boundary to inner plexiform layer/inner nuclear layer boundary, was 68.0 µm (sd:4.0, range:58-77). There was no correlation with sex or age. Fifty-three children manage to complete two, and 41 children three acceptable measurement and the mean coefficient of variation was low. CONCLUSION: The ganglion cell layer thickness differs according to which OCT device that is used, and the population examined. This makes normative data essential to accurately interpret results. Swept source OCT of the macula have excellent repeatability and the examination well tolerated in most children making it an investigation useful for diagnosing and following diseases in the optic pathways.

Initial Training for Mental Health Peer Support Workers: Systematized Review and International Delphi Consultation.

BACKGROUND: Initial training is essential for the mental health peer support worker (PSW) role. Training needs to incorporate recent advances in digital peer support and the increase of peer support work roles internationally. There is a lack of evidence on training topics that are important for initial peer support work training and on which training topics can be provided on the internet. OBJECTIVE: The objective of this study is to establish consensus levels about the content of initial training for mental health PSWs and the extent to which each identified topic can be delivered over the internet. METHODS: A systematized review was conducted to identify a preliminary list of training topics from existing training manuals. Three rounds of Delphi consultation were then conducted to establish the importance and web-based deliverability of each topic. In round 1, participants were asked to rate the training topics for importance, and the topic list was refined. In rounds 2 and 3, participants were asked to rate each topic for importance and the extent to which they could be delivered over the internet. RESULTS: The systematized review identified 32 training manuals from 14 countries: Argentina, Australia, Brazil, Canada, Chile, Germany, Ireland, the Netherlands, Norway, Scotland, Sweden, Uganda, the United Kingdom, and the United States. These were synthesized to develop a preliminary list of 18 topics. The Delphi consultation involved 110 participants (49 PSWs, 36 managers, and 25 researchers) from 21 countries (14 high-income, 5 middle-income, and 2 low-income countries). After the Delphi consultation (round 1: n=110; round 2: n=89; and round 3: n=82), 20 training topics (18 universal and 2 context-specific) were identified. There was a strong consensus about the importance of five topics: lived experience as an asset, ethics, PSW well-being, and PSW role focus on recovery and communication, with a moderate consensus for all other topics apart from the knowledge of mental health. There was no clear pattern of differences among PSW, manager, and researcher ratings of importance or between responses from participants in countries with different resource levels. All training topics were identified with a strong consensus as being deliverable through blended web-based and face-to-face training (rating 1) or fully deliverable on the internet with moderation (rating 2), with none identified as only deliverable through face-to-face teaching (rating 0) or deliverable fully on the web as a stand-alone course without moderation (rating 3). CONCLUSIONS: The 20 training topics identified can be recommended for inclusion in the curriculum of initial training programs for PSWs. Further research on web-based delivery of initial training is needed to understand the role of web-based moderation and whether web-based training better prepares recipients to deliver web-based peer support.

Distribution of cerebral microbleeds in the East and West: Individual participant meta-analysis.

OBJECTIVE: We investigated differences in the anatomical distribution of cerebral microbleeds (CMBs) on MRI, hypothesized to indicate the type of underlying cerebral small vessel disease (SVD), between Eastern and Western general populations. METHODS: We analyzed data from 11 studies identified by a PubMed search between 1996 and April 2014 according to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data. Study quality measures indicated low or medium risk of bias. We included stroke-free participants from populations aged between 55 and 75 years, categorized by geographic location (Eastern or Western). We categorized CMB distribution (strictly lobar, deep and/or infratentorial [D/I], or mixed [i.e., CMBs located in both lobar and D/I regions]). We tested the hypothesis that Eastern and Western populations have different anatomical distributions of CMBs using multivariable mixed effects logistic regression analyses adjusted for age, sex, and hypertension and clustering by institution. RESULTS: Among 8,595 stroke-free individuals (mean age [SD] 66.7 [5.6] years; 48% male; 42% from a Western population), 624 (7.3%) had CMBs (strictly lobar in 3.1%; D/I or mixed in 4.2%). In multivariable mixed effects models, Eastern populations had higher odds of D/I or mixed CMBs (adjusted odds ratio 2.78, 95% confidence interval [CI] 1.77-4.35) compared to Western populations. Eastern populations had a higher number of D/I or mixed CMBs (adjusted prevalence ratio 2.83, 95% CI 1.27-6.31). CONCLUSIONS: Eastern and Western general populations have different anatomical distributions of CMBs, suggesting differences in the spectrum of predominant underlying SVDs, with potential implications for SVD diagnosis and treatment.

Baseline White Matter Hyperintensities and Hippocampal Volume are Associated With Conversion From Normal Cognition to Mild Cognitive Impairment in the Framingham Offspring Study.

INTRODUCTION: We examined associations between magnetic resonance imaging (MRI) markers of cerebrovascular disease and neurodegeneration with mild cognitive impairment (MCI) diagnosis at baseline and conversion from normal cognition to MCI at follow-up. METHODS: Framingham Offspring participants underwent brain MRI and neuropsychological assessment at baseline (n=1049) and follow-up (n=561). Participants were classified at baseline and at follow-up as cognitively normal or MCI using sensitive neuropsychological criteria. White matter hyperintensity (WMH) volume, covert brain infarcts, hippocampal volume, and total cerebral brain volume were quantified. RESULTS: Baseline measures of WMH and hippocampal volume were associated with MCI status cross-sectionally and also with conversion from normal cognition to MCI at 6.5-year follow-up. Annualized change rates in total cerebral brain volume and hippocampal volume were associated with conversion from normal cognition to MCI to follow-up. DISCUSSION: Baseline WMH and hippocampal volume are markers that are both associated with conversion from normal cognition to MCI, highlighting the role of both vascular lesions and neurodegeneration in MCI.

Practical risk score for 5-, 10-, and 20-year prediction of dementia in elderly persons: Framingham Heart Study.

INTRODUCTION: With a rapidly aging population, general practitioners are confronting the challenge of how to determine those who are at greatest risk for dementia and potentially need more specialized follow-up to mitigate symptoms early in its course. We created a practical dementia risk score and provided individualized estimates of future dementia risk. METHODS: Using the Framingham Heart Study data, we built our prediction model using Cox proportional hazard models and developed a point system for the risk score and risk estimates. RESULTS: The score system used total points ranging from -1 to 31 and stratifies individuals into different levels of risk. We estimated 5-, 10-, and 20-year dementia risk prediction and incorporated these into the points system. DISCUSSION: This risk score system provides a practical tool because all included predictors are easy to assess by practitioners. It can be used to estimate future probabilities of dementia for individuals.

Association of descending thoracic aortic plaque with brain atrophy and white matter hyperintensities: The Framingham Heart Study.

BACKGROUND AND AIMS: Aortic atherosclerosis is an aggregate marker of vascular risk factor exposure and has been associated with intracranial atherosclerosis and stroke. We hypothesized that atherosclerosis of the descending aorta (DAo) could be a risk marker for brain aging and injury. METHODS: We evaluated 1527 participants (mean age 59.9 years, 53.5% women) in the Framingham Offspring cohort who underwent both aortic and brain MRI. Participants were free of clinical stroke, dementia, or other neurological illness at the time of axial MRI of the thoracic and abdominal DAo and subsequent brain MRI. We related the prevalence and burden of aortic plaque to total cerebral brain volume (TCBV) and white matter hyperintensity volume (WMHV). An additional analysis compared incidence of stroke or TIA in participants with and without DAo plaques. RESULTS: Presence of thoracic DAo plaque (8%) was associated with decreased TCBV in sex-pooled analysis (-0.77, SE 0.25, p = 0.002, equivalent to 4.5 years of aging) and with increased WMHV only in men (0.26, SE 0.12, p = 0.032, equivalent to 6.5 years aging). We observed similar associations of DAo plaque burden with TCBV and WMHV. There were 43 strokes and 11 TIAs in prospective follow-up (median 7 years). Presence of DAo plaque was not associated with subsequent stroke or TIA. CONCLUSIONS: In this cross-sectional community-based study, we found DAo plaque is associated with accelerated brain aging. These data underscore the potential implications of incidentally identified subclinical aortic atherosclerosis and question whether targeted intervention in these high risk individuals can modulate cognitive decline.

Overweight, Obesity, and Survival After Stroke in the Framingham Heart Study.

BACKGROUND: We investigated how body weight affects survival after stroke, leveraging the availability of multiple prestroke body mass index (BMI) measurements and using a nested case-control design in a community-based sample. METHODS AND RESULTS: We compared all-cause mortality in participants stratified by prestroke weight. Separate analyses were performed for ischemic stroke and all stroke and for age-, sex-, and BMI category-matched stroke-free controls. Participants were grouped into BMI categories and followed for up to 10 years. Differences in survival were tested for interaction by case status. In sensitivity analysis, to exclude those with prestroke weight loss, we restricted the reference group to participants with 2 consistently normal BMI measurements within 10 years before stroke/matching. There were 782 stroke cases (age 71±9, 51% female participants, 87% ischemic stroke) and 2346 controls (age 72±9, 51% female participants). Overweight participants with ischemic stroke had a lower mortality compared with those with normal weight (hazard ratio [HR]=0.70, 95%CI 0.55-0.90, P=0.005). The association of reduced mortality with BMI ≥25, compared with normal-weight BMI 18.5 to <25, was pronounced among ischemic stroke cases but diminished with inclusion of hemorrhagic strokes (case-control interaction P=0.051 and P=0.130, respectively). Compared with participants with stable normal weight, moderately increased weight was protective after ischemic stroke (overweight HR=0.72, 95%CI 0.53-0.99, P=0.041). CONCLUSIONS: Overweight and mildly obese participants had better 10-year survival after ischemic stroke compared with normal-weight participants, even after excluding persons with recent prestroke weight loss. There may be unknown protective factors associated with a moderately increased body weight before stroke.

Cerebral Microbleeds as Predictors of Mortality: The Framingham Heart Study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMB) represent a common magnetic resonance imaging marker of cerebral small vessel disease, increasingly recognized as a subclinical marker of stroke and dementia risk. CMB detection may reflect the cumulative effect of vascular risk burden and be a marker of higher mortality. We investigated the relation of CMB to risk of death in community dwelling participants free of stroke and dementia. METHODS: We evaluated 1963 Framingham Original and Offspring Cohort participants (mean age 67 years; 54% women) with available brain magnetic resonance imaging and mortality data. Using Cox proportional hazards models, we related CMB to all-cause, cardiovascular, and stroke-related mortality. RESULTS: Participants with CMB (8.9%) had higher prevalence of cardiovascular risk factors and use of preventive medications. During a mean follow-up of 7.2±2.6 years, we observed 296 deaths. In age- and sex-adjusted analysis, CMB were associated with increased all-cause mortality (hazards ratio, 1.39; 95% confidence interval 1.03-1.88), a relation that was no longer significant after adjustment for cardiovascular risk and preventive medication use (hazards ratio, 1.15; 95% confidence interval, 0.82-1.63). CONCLUSIONS: CMBs may represent the deleterious effect of cardiovascular risk factors in the cerebral vasculature. Although their presence was associated with increased all-cause mortality, the effect was no longer present after accounting for vascular risk factors and preventive treatment use. Further studies are required to clarify the role of cardiovascular preventive therapies for prevention of mortality in persons with incidental detection of CMB.

Revised Framingham Stroke Risk Profile to Reflect Temporal Trends.

BACKGROUND: Age-adjusted stroke incidence has decreased over the past 50 years, likely as a result of changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham Stroke Risk Profile (FSRP) might better predict current risks in the FHS (Framingham Heart Study) and other cohorts. We compared the accuracy of the standard (old) and of a revised (new) version of the FSRP in predicting the risk of all-stroke and ischemic stroke and validated this new FSRP in 2 external cohorts, the 3C (3 Cities) and REGARDS (Reasons for Geographic and Racial Differences in Stroke) studies. METHODS: We computed the old FSRP as originally described and a new model that used the most recent epoch-specific risk factor prevalence and hazard ratios for individuals ≥55 years of age and for the subsample ≥65 years of age (to match the age range in REGARDS and 3C studies, respectively) and compared the efficacy of these models in predicting 5- and 10-year stroke risks. RESULTS: The new FSRP was a better predictor of current stroke risks in all 3 samples than the old FSRP (calibration χ2 of new/old FSRP: in men: 64.0/12.1, 59.4/30.6, and 20.7/12.5; in women: 42.5/4.1, 115.4/90.3, and 9.8/6.5 in FHS, REGARDS, and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared with blacks. CONCLUSIONS: A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors.

Stroke as the Initial Manifestation of Atrial Fibrillation: The Framingham Heart Study.

BACKGROUND AND PURPOSE: To prevent strokes that may occur as the first manifestation of atrial fibrillation (AF), screening programs have been proposed to identify patients with undiagnosed AF who may be eligible for treatment with anticoagulation. However, the frequency with which patients with AF present with stroke as the initial manifestation of the arrhythmia is unknown. METHODS: We estimated the frequency with which AF may present as a stroke in 1809 community-based Framingham Heart Study participants with first-detected AF and without previous strokes, by tabulating the frequencies of strokes occurring on the same day, within 30 days before, 90 days before, and 365 days before first-detected AF. Using previously reported AF incidence rates, we estimated the incidence of strokes that may represent the initial manifestation of AF. RESULTS: We observed 87 strokes that occurred ≤1 year before AF detection, corresponding to 1.7% on the same day, 3.4% within 30 days before, 3.7% within 90 days before, and 4.8% ≤1 year before AF detection. We estimated that strokes may present as the initial manifestation of AF at a rate of 2 to 5 per 10 000 person-years, in both men and women. CONCLUSIONS: We observed that stroke is an uncommon but measureable presenting feature of AF. Our data imply that emphasizing cost-effectiveness of population-wide AF-screening efforts will be important given the relative infrequency with which stroke represents the initial manifestation of AF.

Effects of white matter integrity and brain volumes on late life depression in the Framingham Heart Study.

BACKGROUND: It is unclear whether brain white matter hyperintensities (WMHI) causes or is a result of late life depression. We used the Framingham Heart Study offspring to examine whether indices of brain aging are related to incident depression in the elderly. METHODS: The Center for Epidemiologic Studies Depression Scale (CES-D) was administered along with a brain MRI scan at baseline and was re-administered (n = 1212) at an average 6.6 + 0.6 year follow-up. The outcomes (i) change in CES-D scores from baseline; (ii) depression defined as CES-D ≥16; (iii) severe depression defined as CES-D ≥21; and (iv) CES-D cutoff scores and/or on antidepressant were used. RESULTS: Among those who did not have depression at baseline, 9.1% (n = 110) developed depression, 4.0% (n = 48) developed severe depressive symptoms, and 11.1% (n = 135) were put on antidepressants. When depressive symptoms only was the outcome, we found that baseline WMHI was positively associated with change in CES-D scores and that those with an extensive WMHI at baseline had a high risk of developing severe depressive symptoms; the relationship was strengthened in the absence of cardiovascular diseases. In contrast, when depressive symptoms or taking antidepressant was the outcome, larger total cerebral brain volume and temporal lobe brain volume, but not WMHI, were negatively associated with the development of depression. CONCLUSIONS: Brain WMHI is a probable risk factor for vascular depression in the elderly. The depression outcomes with and without antidepressant were related to different brain pathologies. Copyright © 2016 John Wiley & Sons, Ltd.

Pulse Pressure Is Associated With Early Brain Atrophy and Cognitive Decline: Modifying Effects of APOE-ε4.

We investigated whether midlife pulse pressure is associated with brain atrophy and cognitive decline, and whether the association was modified by apolipoprotein-E ε4 (APOE-ε4) and hypertension. Participants (549 stroke-free and dementia-free Framingham Offspring Cohort Study participants, age range=55.0 to 64.9 y) underwent baseline neuropsychological and magnetic resonance imaging (subset, n=454) evaluations with 5- to 7-year follow-up. Regression analyses investigated associations between baseline pulse pressure (systolic-diastolic pressure) and cognition, total cerebral volume and temporal horn ventricular volume (as an index of smaller hippocampal volume) at follow-up, and longitudinal change in these measures. Interactions with APOE-ε4 and hypertension were assessed. Covariates included age, sex, education, assessment interval, and interim stroke. In the total sample, baseline pulse pressure was associated with worse executive ability, lower total cerebral volume, and greater temporal horn ventricular volume 5 to 7 years later, and longitudinal decline in executive ability and increase in temporal horn ventricular volume. Among APOE-ε4 carriers only, baseline pulse pressure was associated with longitudinal decline in visuospatial organization. Findings indicate arterial stiffening, indexed by pulse pressure, may play a role in early cognitive decline and brain atrophy in mid to late life, particularly among APOE-ε4 carriers.

Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study.

OBJECTIVE: We related a panel of inflammatory biomarkers to risk of incident ischemic stroke (IIS) in a community-dwelling sample. METHODS: Stroke-free Framingham offspring attending examination cycle 7 (1998-2001) had 15 circulating inflammatory biomarkers measured. Cox proportional hazard models were used to calculate the hazard ratios (HRs) of IIS per SD increment of each biomarker. Model 1 included age and sex. Model 2 additionally adjusted for systolic blood pressure, hypertension treatment, current smoking, diabetes, cardiovascular disease, and atrial fibrillation. The continuous net reclassification improvement was used to assess the improvement in IIS risk prediction of statistically significant biomarkers from our main analysis over traditional stroke risk factors. RESULTS: In 3,224 participants (mean age 61 ± 9 years, 54% women), 98 experienced IIS (mean follow-up of 9.8 [±2.2] years). In model 1, ln-C-reactive protein (ln-CRP) (HR 1.28, 95% confidence interval [CI] 1.04-1.56), ln-tumor necrosis factor receptor 2 (ln-TNFR2) (HR 1.33, 95% CI 1.09-1.63), ln-total homocysteine (ln-tHcy) (HR 1.32, 95% CI 1.11-1.58), and vascular endothelial growth factor (VEGF) (HR 1.25, 95% CI 1.07-1.46) were associated with risk of IIS. All associations, except for ln-CRP, remained significant in model 2 (ln-TNFR2: HR 1.24, 95% CI 1.02-1.51; ln-tHcy: HR 1.20, 95% CI 1.01-1.43; and VEGF: HR 1.21, 95% CI 1.04-1.42). The addition of these 4 biomarkers to the clinical Framingham Stroke Risk Profile score improved stroke risk prediction (net reclassification improvement: 0.34, 0.12-0.57; p < 0.05). CONCLUSIONS: Higher levels of 4 biomarkers-CRP, tHcy, TNFR2, and VEGF-increased risk of IIS and improved the predictive ability of the Framingham Stroke Risk Profile score. Further research is warranted to explore their role as potential therapeutic targets.

Population Normative Data for the CERAD Word List and Victoria Stroop Test in Younger- and Middle-Aged Adults: Cross-Sectional Analyses from the Framingham Heart Study.

BACKGROUND/STUDY CONTEXT: To provide baseline normative data on tests of verbal memory and executive function for nondemented younger- and middle-aged adults. METHODS: The Consortium to Establish a Registry for Alzheimer's Disease word list memory task (CERAD-WL) and Victoria Stroop Test (VST) were administered to 3362 Framingham Heart Study (FHS) volunteer participants aged 24-78 years. Analyses of the effects of age, gender, and education were conducted. Normative data on traditional measures and error responses are reported for each test. RESULTS: Traditional measures were significantly associated with both age and education in this cohort. Error responses also evidenced significant age and education effects. CONCLUSION: These data provide a normative comparison for assessment of verbal memory and executive functioning capabilities in younger- and middle-aged adults and may be utilized as a tool for preclinical studies of disease in this population.

Interaction Between Midlife Blood Glucose and APOE Genotype Predicts Later Alzheimer's Disease Pathology.

Elevated blood glucose and the apolipoprotein (APOE) ɛ4 allele have both been associated with increased dementia risk; however, the neuropathological mechanisms underlying these associations remain unclear. We examined the impact of APOE genotype and midlife blood glucose on post-mortem vascular and Alzheimer's disease (AD) neuropathology. Ninety-four participants from the Framingham Heart Study without diagnosed diabetes underwent health examination at midlife and brain autopsy at death. Histopathological measures of vascular and AD neuropathology were obtained and analyzed. Results demonstrated that, among APOE ɛ4 carriers, elevated blood glucose was associated with more severe AD pathology. There was no such relationship with vascular pathology. In a relatively healthy sample with low vascular risk burden, midlife elevated blood glucose was associated with greater AD pathology among APOE ɛ4 carriers. A better understanding of interactive effects of APOE genotype and vascular risk on neuropathology has implications for identification of individuals at risk for decline and long-term preventive treatment.

Association between atrial fibrillation and volumetric magnetic resonance imaging brain measures: Framingham Offspring Study.

BACKGROUND: The increased risk of stroke and cognitive impairment associated with atrial fibrillation (AF) is well documented. However, there is a paucity of research investigating the relations between AF and brain morphology. OBJECTIVE: The purpose of this study was to investigate the association between AF and brain volume measures on magnetic resonance imaging (MRI). METHODS: The study sample included stroke- and dementia-free participants who attended the Framingham Heart Study offspring cohort 7th examination cycle (1999-2005) and underwent contemporaneous MRI. We examined the association between prevalent AF and brain volume measures (total cerebral volume, frontal lobe volume, temporal lobe volume, temporal horn volume, hippocampal volume, and white matter hyperintensity volume) with linear regression. We first adjusted models for age and sex, and then for vascular risk factors and APOE4. RESULTS: We studied 2144 individuals (mean age 61.8 ± 9.3 years; 54% women); 73 participants (3.4%) had prevalent AF at the time of MRI. In age- and sex-adjusted models, AF was inversely associated with total cerebral brain volume, frontal brain volume, and temporal brain volume. After further adjustment for vascular risk factors and APOE4, AF remained associated with frontal brain volume. CONCLUSION: After accounting for vascular risk factor burden, prevalent AF was associated with lobar indexes of vascular brain aging but not with expected white matter changes.

Neck Circumference, Brain Imaging Measures, and Neuropsychological Testing Measures.

BACKGROUND: Perivascular fat may have direct effects on local vascularity. Neck fat is associated with carotid intimal thickness, a predictor of brain aging outcomes. This study investigated whether neck circumference, an estimation of neck fat, has unique associations with brain aging outcomes. METHODS: The study sample (n = 2082, 53.5% women, mean age 60.9 years) was derived from Framingham Heart Study participants with brain magnetic resonance imaging (MRI) and neuropsychological (NP) test measures. Multivariable-adjusted regressions examined cross-sectional associations of neck circumference with brain MRI and NP test measures. Models were also constructed with waist circumference and body mass index (BMI) as exposures. RESULTS: A 1 standard deviation (2.8 cm [women]; 2.9 cm [men]) increment in neck circumference was associated with lower total cerebral brain volume (ß = -.22, P = .0006) and lower frontal brain volume (ß = -.55, P < .0001). However, a similar association was observed for both waist circumference and BMI. There were no associations between neck circumference and NP test measures after full covariate adjustment. CONCLUSIONS: There were no unique associations between neck circumference and brain MRI or NP measures. Consistent with prior observations, all adiposity measures showed associations with more adverse brain MRI and NP measures, suggesting a global association of generalized adiposity.

Neuropsychological Criteria for Mild Cognitive Impairment and Dementia Risk in the Framingham Heart Study.

OBJECTIVES: To refine mild cognitive impairment (MCI) diagnostic criteria, we examined progression to dementia using two approaches to identifying MCI. METHODS: A total of 1203 Framingham Heart Study participants were classified at baseline as cognitively normal or MCI (overall and four MCI subtypes) via conventional Petersen/Winblad criteria (single cognitive test impaired per domain, >1.5 SD below expectations) or Jak/Bondi criteria (two tests impaired per domain, >1 SD below norms). Cox proportional hazards models were constructed to examine the association between each MCI definition and incident dementia. RESULTS: The Petersen/Winblad criteria classified 34% of participants as having MCI while the Jak/Bondi criteria classified 24% as MCI. Over a mean follow-up of 9.7 years, 58 participants (5%) developed incident dementia. Both MCI criteria were associated with incident dementia [Petersen/Winblad: hazards ratio (HR) = 2.64; p-value=.0002; Jak/Bondi: HR=3.30; p-value <.0001]. When both MCI definitions were included in the same model, only the Jak/Bondi definition remained statistically significantly associated with incident dementia (HR=2.47; p-value=.008). Multi-domain amnestic and single domain non-amnestic MCI subtypes were significantly associated with incident dementia for both diagnostic approaches (all p-values <.01). CONCLUSIONS: The Jak/Bondi MCI criteria had a similar association with dementia as the conventional Petersen/Winblad MCI criteria, despite classifying ~30% fewer participants as having MCI. Further exploration of alternative methods to conventional MCI diagnostic criteria is warranted. (JINS, 2016, 22, 937-943).

Carotid Atherosclerosis and Cerebral Microbleeds: The Framingham Heart Study.

BACKGROUND: Carotid atherosclerosis is associated with subclinical ischemic cerebrovascular disease, but its role in hemorrhage-prone small vessel disease-represented by cerebral microbleed (CMB)-is unclear, although vascular risk factors underlie both conditions. We hypothesized that persons with carotid atherosclerosis would have higher risk of CMB, particularly in deep regions. METHODS AND RESULTS: We studied 1243 participants in the Framingham Offspring Study (aged 56.9±8.8 years; 53% women) with carotid ultrasound available on 2 occasions (1995-1998 and 2005-2008) prior to brain magnetic resonance imaging. Using multivariable logistic regression, we related baseline carotid stenosis, baseline intima-media thickness, and site-specific carotid intima-media thickness progression (at internal and common carotid locations) to the prevalence and location (lobar or deep plus mixed) of CMB. In addition, we assessed effect modification by lipid levels and use of statin and antithrombotic medications. Carotid stenosis ≥25% (a marker of cerebrovascular atherosclerosis) was associated with presence of CMB overall (Odds Ratio 2.20, 95% CI 1.10-4.40) and at deep and mixed locations (odds ratio 3.60, 95% CI 1.23-10.5). Baseline carotid intima-media thickness was not associated with CMB. Progression of common carotid artery intima-media thickness among persons on hypertension treatment was associated with lower risk of deep and mixed CMB (odds ratio per SD 0.41, 95% CI 0.18-0.96). CONCLUSIONS: Cumulative vascular risk factor exposure may increase the risk of CMB, especially in deep regions. The apparent paradoxical association of carotid intima-media thickness progression with lower risk of CMB may reflect benefits of intensive vascular risk factor treatment among persons with higher cardiovascular risk and deserves further investigation. If replicated, the results may have potential implications for assessment of preventive and therapeutic interventions for subclinical cerebral hemorrhage.

Lifelong Reading Disorder and Mild Cognitive Impairment: Implications for Diagnosis.

Although neuropsychological tests are commonly used in the evaluation of possible mild cognitive impairment (MCI), poor test scores may be indicative of factors other than neurological compromise. The current study assessed the role of lifelong reading disorder on MCI classification. Community dwelling older adults with a suspected developmental reading disorder were identified by inference based on reading test performance. Individuals with a suspected reading disorder were significantly more likely to perform at a level consistent with MCI on several commonly used neuropsychological tests. The findings suggest a relationship between a history of reading disorder and MCI classification.