Change in cardiovascular health and rate of cognitive decline in older adults: a 15-year population-based study.

BACKGROUND: Previous research on associations between cardiovascular health, measured at a single timepoint, and rate of age-related cognitive decline shows divergent findings dependent on the participants' age and the health metric studied. The aim of this study was to add to the knowledge in this field by investigating whether change in cardiovascular health, assessed with Life's Simple 7 (LS7) score, is associated with rate of cognitive change in young-old and old-old adults. METHODS: The study included 1022 participants aged ≥ 60 years from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, and perceptual speed) across up to 15 years. LS7, composed of seven cardiovascular health metrics (smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure), was assessed at baseline and at the 6-year follow-up. Change in LS7 was calculated as the difference between baseline and 6 years (range - 5 to 8 points) and categorised into worse (-5 to -2 points), stable (-1 to 1 points), and improved (2 to 8 points). Change in cognitive performance as a function of LS7 change categories was estimated using linear mixed-effects models. RESULTS: Participants were classified as stable (67.1%), improved (21.0%), or worse (11.8%) according to changes in LS7 score. Both the worse and improved categories were associated with faster cognitive decline. Age-stratified analyses revealed that worsening of LS7 was clearly associated with faster cognitive decline in the old-old (≥ 78 years), whereas improvement tended be associated with faster cognitive decline in the young-old (< 78 years) group. CONCLUSIONS: Change in cardiovascular health in old age may lead to accelerated cognitive decline, particularly in late senescence. These results suggest that it is important to monitor and maintain cardiovascular health status in very old adults.

Cardiovascular health and rate of cognitive decline in preclinical dementia: A 12-year population-based study.

OBJECTIVE: We investigated whether vascular risk factors (VRFs), assessed with Life's Simple 7 (LS7), are associated with the rate of cognitive decline in the years preceding a dementia diagnosis. METHOD: This study included 1,449 stroke-free participants aged ≥60 years from the Swedish National Study on Aging and Care in Kungsholmen, who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, perceptual speed) across 12 years. The LS7 score, assessed at baseline, included smoking, diet, physical activity, body mass index, plasma glucose, total cholesterol, and blood pressure. Preclinical dementia was defined as being dementia-free at baseline and diagnosed with dementia during follow-up. Level and change in cognitive performance as a function of LS7 category (poor vs. intermediate to optimal) and future dementia status were estimated using linear mixed-effect models. RESULTS: Participants who later developed dementia had, on average, a poorer LS7 score compared to those who remained dementia-free. For individuals aged 60-72 years, poor diet was associated with accelerated decline in perceptual speed (ß = -0.05, 95% CI [-0.08, -0.02]), and a poor glucose score was associated with faster rates of verbal fluency (ß = -0.019, 95% CI [-0.09, -0.01]) and global cognitive (ß = -0.028, 95% CI [-0.06, 0.00]) decline in the preclinical dementia group. CONCLUSIONS: VRFs exacerbate rate of cognitive decline in the years preceding a dementia diagnosis. This effect was most pronounced in young-old age and primarily driven by diet and glucose. The effect of VRFs may be especially detrimental for cognitive decline trajectories of individuals with impending dementia. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission.

PURPOSE: Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA). METHODS: FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level. RESULTS: Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912). CONCLUSION: Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.

Sex differences in brain atrophy in dementia with Lewy bodies.

INTRODUCTION: Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS: We included 436 patients from the European-DLB consortium and the Mayo Clinic. Sex differences and sex-by-age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males). RESULTS: We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex-by-age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION: We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. HIGHLIGHTS: Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

Precision medicine in neurodegeneration: the IHI-PROMINENT project.

Neurodegenerative diseases are one of the most important contributors to morbidity and mortality in the elderly. In Europe, over 14 million people are currently living with dementia, at a cost of over 400 billion EUR annually. Recent advances in diagnostics and approval for new pharmaceutical treatments for Alzheimer's disease (AD), the most common etiology of dementia, heralds the beginning of precision medicine in this field. However, their implementation will challenge an already over-burdened healthcare systems. There is a need for innovative digital solutions that can drive the related clinical pathways and optimize and personalize care delivery. Public-private partnerships are ideal vehicles to tackle these challenges. Here we describe the Innovative Health Initiative (IHI) public-private partnership project PROMINENT that has been initiated by connecting leading dementia researchers, medical professionals, dementia patients and their care partners with the latest innovative health technologies using a precision medicine based digital platform. The project builds upon the knowledge and already implemented digital tools from several collaborative initiatives that address new models for early detection, diagnosis, and monitoring of AD and other neurodegenerative disorders. The project aims to provide support to improvement efforts to each aspect of the care pathway including diagnosis, prognosis, treatment, and data collection for real world evidence and cost effectiveness studies. Ultimately the PROMINENT project is expected to lead to cost-effective care and improved health outcomes.

Adopting transfer learning for neuroimaging: a comparative analysis with a custom 3D convolution neural network model.

BACKGROUND: In recent years, neuroimaging with deep learning (DL) algorithms have made remarkable advances in the diagnosis of neurodegenerative disorders. However, applying DL in different medical domains is usually challenged by lack of labeled data. To address this challenge, transfer learning (TL) has been applied to use state-of-the-art convolution neural networks pre-trained on natural images. Yet, there are differences in characteristics between medical and natural images, also image classification and targeted medical diagnosis tasks. The purpose of this study is to investigate the performance of specialized and TL in the classification of neurodegenerative disorders using 3D volumes of 18F-FDG-PET brain scans. RESULTS: Results show that TL models are suboptimal for classification of neurodegenerative disorders, especially when the objective is to separate more than two disorders. Additionally, specialized CNN model provides better interpretations of predicted diagnosis. CONCLUSIONS: TL can indeed lead to superior performance on binary classification in timely and data efficient manner, yet for detecting more than a single disorder, TL models do not perform well. Additionally, custom 3D model performs comparably to TL models for binary classification, and interestingly perform better for diagnosis of multiple disorders. The results confirm the superiority of the custom 3D-CNN in providing better explainable model compared to TL adopted ones.

Stable cerebrospinal fluid neurogranin and ß-site amyloid precursor protein cleaving enzyme 1 levels differentiate predementia Alzheimer's disease patients.

Cerebrospinal fluid (CSF) ß-site amyloid precursor protein cleaving enzyme 1 (BACE1), neurogranin and the neurogranin/BACE1 ratio are proposed markers for Alzheimer's disease. BACE1 is also a drug target. However, CSF levels may differ between early-stage amyloid plaque formation (A) and later stage downstream tau-tangle pathology (T) and neurodegeneration (N) and may be expressed as an A/T/N stage (e.g. A+/T-/N or A+/T+/N+). Whether BACE1 and neurogranin levels are persistent traits or change with disease progression is unknown. The aim of this study was to investigate whether CSF neurogranin and BACE1 concentrations differ between A/T/N stages, whether these change over time and correlate with memory decline. This may have implications for patient selection in future trials. We used CSF markers to determine A/T/N stage using amyloid beta42/40 ratio, p-tau181 and total-tau respectively in predementia Alzheimer's disease cases (n = 176) [including cases that progressed to dementia (n = 10)] and controls (n = 74) from the Norwegian Dementia Disease Initiation cohort. We selected cases at the presumed early (A+/T-/N-, n = 86) and late stages (A+/T+/N+, n = 90) of the Alzheimer's disease continuum and controlled with normal markers (A-/T-/N-, n = 74). A subset of subjects in all A/T/N groups underwent repeat CSF sampling at approximately 2-year intervals up to 6 years from baseline. Using linear mixed models, longitudinal measurements of CSF BACE1 and neurogranin levels in A+/T-/N- and A+/T+/N+ as compared to A-/T-/N- healthy controls were performed. Next, we measured changes in CSF BACE1 and neurogranin levels in cases that progressed from A-/T-/N- to A+/T-/N- (n = 12), from A+/T-/N- to A+/T or N+ (n = 12), remained stable A+/T-/N- (n = 26), remained stable A+/T+/N+ (n = 28) compared with controls remaining stable A-/T-/N- (n = 33). Lastly, associations between these markers and memory decline were assessed. Compared with A-/T-/N- healthy controls, neurogranin was unaltered in A+/T-/N- (n.s.) but higher in A+/T+/N+ (P < 0.0001). In contrast, BACE1 was lower in A+/T-/N- (P < 0.05) and higher in A+/T+/N+ (P < 0.0001). The neurogranin/BACE1 ratio was increased in both A+/T-/N- (P < 0.05) and A+/T+/N+ (P < 0.0001) groups as compared to A-/T-/N- healthy controls and was more strongly associated with memory decline (b = -0.29, P = 0.0006) than neurogranin (b = -0.20, P = 0.002) and BACE1 (b = -0.13, P = 0.046). Neurogranin and BACE1 level differences remained stable over time not only within A/T/N groups but also in patients progressing to more pathological A/T/N stages (e.g. progressing from A+/T-/N- to A + T or N+) and in cases progressing to dementia. Our results suggest that neurogranin and BACE1 levels may differentiate pathomechanistic Alzheimer's disease subgroups, putatively with different options for treatment.

Adverse effects of levodopa/carbidopa intrajejunal gel treatment: A single-center long-term follow-up study.

OBJECTIVES: Levodopa/carbidopa intrajejunal gel (LCIG) is an effective therapeutic strategy to overcome levodopa-induced motor complications in advanced Parkinson's disease (PD). However, it requires invasive percutaneous endoscopic gastrojejunostomy (PEG-J) and may be associated with serious adverse effects (AE). In this study, we aimed to evaluate long-term AEs related to LCIG treatment in a large homogenous cohort of advanced PD patients. METHODS: One hundred three consecutive PD patients were regularly monitored for LCIG-related, PEG-J-related, and device-related AEs up to 14 years. Incidence of AEs was studied in time applying a time-to-event analysis and Cox proportional hazard model with age, disease duration, gender, and recurrent AE as covariates. Health-related quality of life (HRQoL) was estimated at each visit and compared to HRQoL before the LCIG treatment. RESULTS: Among 296 AEs noted, 48.8% were LCIG-related, 32.4% PEG-J-related, and 19.6% device-related. While most of the studied AEs steadily accumulated throughout the follow-up period, 24.3% of the patients (95% CI 10.1%-36.3%) experienced PEG-J-related AE already within the first days after the PEG-J insertion. Cox model revealed that older patients had higher probability of psychosis, PEG-J- and device-related AEs (p < .05, p < .05, and p = .02) and suggested increased recurrence risk in those with early PEG-J and device-related AEs. Despite relatively high incidence of AEs, HRQoL significantly increased in the follow-up period (p < .0001). CONCLUSION: AEs related to LCIG treatment are common. Therefore, careful patient selection and monitoring throughout the treatment is recommended, especially in those with early side effects. Nevertheless, LCIG significantly improves HRQoL in advanced PD patients on a long term.

Continuous Dopaminergic Stimulation Improves Cortical Maladaptive Changes in Advanced Parkinson's Disease.

BACKGROUND: With the progression of Parkinson's disease (PD), pulsatile treatment with oral levodopa causes maladaptive changes within basal ganglia-thalamo-cortical circuits, which are clinically expressed as motor fluctuations and dyskinesias. At the level of the motor cortex, these changes may be detected using transcranial magnetic stimulation (TMS), as abnormal corticospinal and intracortical excitability and absent response to plasticity protocols. OBJECTIVE: We investigated the effect of continuous dopaminergic stimulation on cortical maladaptive changes related to oral levodopa treatment. METHODS: Twenty patients with advanced PD were tested using TMS within 1 week before and again 6 months after the introduction of levodopa-carbidopa intestinal gel. We measured resting and active motor thresholds, input/output curve, short interval intracortical inhibition curve, cortical silent period, and response to intermittent theta burst stimulation. Patients were clinically assessed with Part III and Part IV of the Movement Disorders Society Unified Parkinson's Disease Rating Scale. RESULTS: Six months after the introduction of levodopa-carbidopa intestinal gel, motor fluctuations scores (P = 0.001) and dyskinesias scores (P < 0.001) were reduced. Resting and active motor threshold (P = 0.012 and P = 0.015) and x-intercept of input/output curve (P = 0.005) were also decreased, while short-interval intracortical inhibition and response to intermittent theta bust stimulation were improved (P = 0.026 and P = 0.031, respectively). Changes in these parameters correlated with clinical improvement. CONCLUSIONS: In patients with advanced PD, switching from intermittent to continuous levodopa delivery increased corticospinal excitability and improved deficient intracortical inhibition and abnormal motor cortex plasticity, along with amelioration of motor fluctuations and dyskinesias. Continuous dopaminergic stimulation ameliorates maladaptive changes inflicted by chronic pulsatile dopaminergic stimulation. © 2022 International Parkinson and Movement Disorder Society.

Association of Plasma p-tau181 and p-tau231 Concentrations With Cognitive Decline in Patients With Probable Dementia With Lewy Bodies.

Importance: Plasma phosphorylated tau (p-tau) has proven to be an accurate biomarker for Alzheimer disease (AD) pathologic characteristics, offering a less expensive and less invasive alternative to cerebrospinal fluid (CSF) and positron emission tomography biomarkers for amyloid-ß and tau. Alzheimer disease comorbid pathologic characteristics are common and are associated with more rapid cognitive decline in patients with dementia with Lewy bodies (DLB); therefore, it is anticipated that plasma p-tau concentrations may have utility in assessing cognitive impairment in individuals with this disorder. Objective: To measure the concentrations of plasma p-tau (p-tau181 and p-tau231) and evaluate their associations with cognitive decline in individuals with probable DLB. Design, Setting, and Participants: This multicenter longitudinal cohort study included participants from the European-DLB (E-DLB) Consortium cohort enrolled at 10 centers with harmonized diagnostic procedures from January 1, 2002, to December 31, 2020, with up to 5 years of follow-up. A total of 1122 participants with plasma samples were available. Participants with acute delirium or terminal illness and patients with other previous major psychiatric or neurologic disorders were excluded, leaving a cohort of 987 clinically diagnosed participants with probable DLB (n = 371), Parkinson disease (n = 204), AD (n = 207), as well as healthy controls (HCs) (n = 205). Main Outcomes and Measures: The main outcome was plasma p-tau181 and p-tau231 levels measured with in-house single molecule array assays. The Mini-Mental State Examination (MMSE) was used to measure cognition. Results: Among this cohort of 987 patients (512 men [51.9%]; mean [SD] age, 70.0 [8.8] years), patients with DLB did not differ significantly regarding age, sex, or years of education from those in the AD group, but the DLB group was older than the HC group and included more men than the AD and HC groups. Baseline concentrations of plasma p-tau181 and p-tau231 in patients with DLB were significantly higher than those in the HC group but lower than in the AD group and similar to the Parkinson disease group. Higher plasma concentrations of both p-tau markers were found in a subgroup of patients with DLB with abnormal CSF amyloid-ß42 levels compared with those with normal levels (difference in the groups in p-tau181, -3.61 pg/mL; 95% CI, -5.43 to -1.79 pg/mL; P = .049; difference in the groups in p-tau231, -2.51 pg/mL; 95% CI, -3.63 to -1.39 pg/mL; P = .02). There was no difference between p-tau181 level and p-tau231 level across confirmed AD pathologic characteristcs based on reduced Aß42 level in CSF in individuals with DLB. In DLB, a significant association was found between higher plasma p-tau181 and p-tau231 levels and lower MMSE scores at baseline (for p-tau181, -0.092 MMSE points; 95% CI, -0.12 to -0.06 MMSE points; P = .001; for p-tau231, -0.16 MMSE points; 95% CI, -0.21 to -0.12 MMSE points; P < .001), as well as more rapid MMSE decline over time. Plasma p-tau181 level was associated with a decrease of -0.094 MMSE points per year (95% CI, -0.144 to -0.052 MMSE points; P = .02), whereas plasma p-tau231 level was associated with an annual decrease of -0.130 MMSE points (95% CI, -0.201 to -0.071 MMSE points; P = .02), after adjusting for sex and age. Conclusions and Relevance: This study suggests that plasma p-tau181 and p-tau231 levels may be used as cost-effective and accessible biomarkers to assess cognitive decline in individuals with DLB.

Complementary pre-screening strategies to uncover hidden prodromal and mild Alzheimer's disease: Results from the MOPEAD project.

INTRODUCTION: The Models of Patient Engagement for Alzheimer's Disease (MOPEAD) project was conceived to explore innovative complementary strategies to uncover hidden prodromal and mild Alzheimer's disease (AD) dementia cases and to raise awareness both in the general public and among health professionals about the importance of early diagnosis. METHODS: Four different strategies or RUNs were used: (a) a web-based (WB) prescreening tool, (2) an open house initiative (OHI), (3) a primary care-based protocol for early detection of cognitive decline (PC), and (4) a tertiary care-based pre-screening at diabetologist clinics (DC). RESULTS: A total of 1129 patients at high risk of having prodromal AD or dementia were identified of 2847 pre-screened individuals (39.7%). The corresponding proportion for the different initiatives were 36.8% (WB), 35.6% (OHI), 44.4% (PC), and 58.3% (DC). CONCLUSION: These four complementary pre-screening strategies were useful for identifying individuals at high risk of having prodromal or mild AD.

A 3D deep learning model to predict the diagnosis of dementia with Lewy bodies, Alzheimer's disease, and mild cognitive impairment using brain 18F-FDG PET.

PURPOSE: The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimer's disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimer's disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare model's performance to that of multiple expert nuclear medicine physicians' readers. MATERIALS AND METHODS: Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimer's disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The model's performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. RESULTS: The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6-100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7-100) in AD, 71.4% (51.6-91.2) in MCI-AD, and 94.7% (90-99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. CONCLUSION: Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.

Pharmacological Medical Treatment of Epilepsy in Patients with Dementia: A Systematic Review.

BACKGROUND: Patients with dementia have an increased risk of developing epilepsy, especially in patients with vascular dementia and Alzheimer's disease. In selecting the optimal anti- epileptic drug (AED), the possible side effects such as drowsiness and worsening of cognitive function should be taken into consideration, together with co-morbidities and type of epilepsy. OBJECTIVE: The current systematic review investigates the efficacy, tolerability, and changes in cognitive function after administration of AED in patients with dementia and epilepsy. METHODS: We searched six databases, including MEDLINE and CENTRAL, checked reference lists, contacted experts, and searched Google Scholar to identify studies reporting randomized trials. Studies identified were independently screened, data extracted, and quality appraised by two researchers. A narrative synthesis was used to report findings. RESULTS: We included one study with 95 patients with Alzheimer's disease randomized to either levetiracetam, lamotrigine, or phenobarbital. No significant differences were found for efficacy, but patients receiving levetiracetam showed an improvement in mini-mental state examination scores and had fewer adverse events. CONCLUSION: High-quality evidence in the form of randomized controlled trials to guide clinicians in choosing an AED in patients with dementia and concomitant epilepsy remains scarce. However, levetiracetam has previously been shown to possibly improve cognition in patients with both mild cognitive impairment and Alzheimer's disease, is better tolerated in the elderly population, and has no clinically relevant interaction with either cholinesterase inhibitors or NMDA receptor antagonists.

The Relationship Between Cardiovascular Health and Rate of Cognitive Decline in Young-Old and Old-Old Adults: A Population-Based Study.

BACKGROUND: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure. OBJECTIVE: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals. METHODS: This cohort study included 1,950 participants aged≥60 years (M = 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function of LS7 categories were estimated using linear mixed-effects models. RESULTS: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (ß= 0.21, 95%CI 0.12-0.29), verbal fluency (ß= 0.08, 0.00-0.16), and global cognition (ß= 0.06, 0.00-0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (< 78 years) group. For the specific metrics, diverging patterns were observed for young-old and old-old individuals. CONCLUSION: Meeting the LS7 criteria for ideal cardiovascular health in younger old age is associated with slower rate of cognitive decline. However, the LS7 criteria may have a different meaning for cognitive function in very old adults.

Identifying relevant outcomes in the progression of Alzheimer's disease; what do patients and care partners want to know about prognosis?

BACKGROUND: Prognostic studies in the context of Alzheimer's disease (AD) mainly predicted time to dementia. However, it is questionable whether onset of dementia is the most relevant outcome along the AD disease trajectory from the perspective of patients and their care partners. Therefore, we aimed to identify the most relevant outcomes from the viewpoint of patients and care partners. METHODS: We used a two-step, mixed-methods approach. As a first step we conducted four focus groups in the Netherlands to elicit a comprehensive list of outcomes considered important by patients (n = 12) and care partners (n = 14) in the prognosis of AD. The focus groups resulted in a list of 59 items, divided into five categories. Next, in an online European survey, we asked participants (n = 232; 99 patients, 133 care partners) to rate the importance of all 59 items (5-point Likert scale). As participants were likely to rate a large number of outcomes as "important" (4) or "very important" (5), we subsequently asked them to select the three items they considered most important. RESULTS: The top-10 lists of items most frequently mentioned as "most important" by patients and care partners were merged into one core outcome list, comprising 13 items. Both patients and care partners selected outcomes from the category "cognition" most often, followed by items in the categories "functioning and dependency" and "physical health." No items from the category "behavior and neuropsychiatry" and "social environment" ended up in our core list of relevant outcomes. CONCLUSION: We identified a core list of outcomes relevant to patients and care partner, and found that prognostic information related to cognitive decline, dependency, and physical health are considered most relevant by both patients and their care partners.

A Cost-Consequence Analysis of Different Screening Procedures in Alzheimer's Disease: Results from the MOPEAD Project.

BACKGROUND: For care planning and support, under-detection and late diagnosis of Alzheimer's disease (AD) is a great challenge. Models of Patient-Engagement for Alzheimer's Disease (MOPEAD) is an EU-funded project aiming at testing different strategies to improve this situation. OBJECTIVE: To make a cost-consequence analysis of MOPEAD. METHODS: Four screening strategies were tested in five countries (Germany, the Netherlands, Slovenia, Spain, and Sweden): 1) a web-approach; 2) Open-House initiative; 3) in primary care; and 4) by diabetes specialists. Persons-at-risk of AD in all strategies were offered referral to a hospital-based specialist. The primary health-economic outcome was the cost per true-positive case (TP) of AD from the screened population. RESULTS: Of 2,847 screened persons, 1,121 screened positive (39%), 402 were evaluated at memory clinics (14%), and 236 got an AD diagnosis (8%). The cost per TP of those screened was €3,115 with the web-approach, €2,722 with the Open-House, €1,530 in primary care, and €1,190 by diabetes specialists. Sensitivity analyses that more likely reflect the real-world situation confirmed the results. The number-needed-to-screen was 30 with the web-approach, 8 with the Open-House and primary care, and 6 with the diabetes specialists.There were country differences in terms of screening rates, referrals to memory clinics, staff-types involved, and costs per TP. CONCLUSION: In primary care and by the diabetes specialist, the costs per TP/screened population were lowest, but the capacity of such settings to identify cases with AD-risk must be discussed. Hence new diagnostic strategies such as web-solutions and Open-House initiatives may be valuable after modifications.

General practitioners' attitude toward early and pre-dementia diagnosis of AD in five European countries-A MOPEAD project survey.

INTRODUCTION: General practitioners (GPs) play a key role in early identification of dementia, yet diagnosis is often missed or delayed in primary care. As part of the multinational Models of Patient Engagement for Alzheimer's Disease project, we assess GPs' attitude toward early and pre-dementia diagnosis of AD and explore barriers to early diagnosis. METHODS: Our survey covered general attitude toward early diagnosis, diagnostic procedures, resources, and opinion on present and future treatment options across five European countries. RESULTS: In total 343 GPs completed the survey; 74% of GPs indicated that an early diagnosis is valuable. There were country-specific differences in GPs' perceptions of reimbursement and time available for the patient. If a drug were available to slow down the progression of AD, 59% of the GPs would change their implementation of early diagnosis. DISCUSSION: Our findings provide insight into GPs' attitudes by exploring differences in perception and management of early diagnosis.

Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project.

INTRODUCTION: We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. METHODS: Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). RESULTS: Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). DISCUSSION: These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.

Central nystagmus in progressive supranuclear palsy: A neglected clinical feature?

BACKGROUND: Progressive supranuclear palsy (PSP) features parkinsonism characterized by early postural instability, falls and prominent eye movement abnormalities that consist of saccadic slowing, followed by gaze limitation. Nystagmus is not considered typical for PSP, being more commonly associated with multiple system atrophy. OBJECTIVES: To describe the prevalence and phenomenology of nystagmus in patients with PSP. METHODS: 42 patients with probable PSP underwent detailed clinical eye movement examination. Patients with nystagmus performed video-nystagmography. T-test, Chi-Square test and Wilcoxon signed-rank test were used to test differences in demographic data, disease duration and PSP subtype between patients with and without nystagmus, and for analysis of video-nystagmographic data. RESULTS: Among 42 patients with PSP, we identified 15 patients (35,7%) with gaze-evoked nystagmus, predominantly horizontal. Clinically, 10/15 patients had symmetrical or asymmetrical gaze - evoked nystagmus (Type 1), while 5/15 patients had dissociated gaze-evoked nystagmus related to internuclear ophthalmoplegia (Type 2). Nystagmus and eye movement abnormalities were further characterized by video-nystagmography. There was no significant difference in age, disease duration or PSP subtypes between patients with and without nystagmus. CONCLUSION: Central nystagmus is present in more than a third of patients with progressive supranuclear palsy. It may present as symmetrical or asymmetrical gaze-evoked nystagmus or as dissociated gaze-evoked nystagmus related to internuclear ophthalmoplegia and probably arises from neurodegeneration of the neural integrator. Nystagmus in PSP has been a hitherto under-described feature and its presence should not deter clinicians from a diagnosis of PSP.

Biomarker counseling, disclosure of diagnosis and follow-up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey.

OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. METHODS: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. RESULTS: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. CONCLUSIONS: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.