Risk and sex-specific trends of dementia and stroke in Italy Compared to European and high-income countries and the world: global implications.

BACKGROUND: Understanding the increasing trends in Italy may inform new prevention strategies and better treatments. We investigated trends and risk factors of dementia, stroke, and ischemic heart disease (IHD) in Italy with the second-oldest population globally, compared to European and high-income countries and the world. METHODS: We analyzed the Global Burden of Disease Study (GBD) 2019 estimates on incidence and burden (i.e., disability and death combined) of the three conditions in both sexes. We also analyzed the burden attributable to 12 modifiable risk factors and their changes during 1990-2019. RESULTS: In 2019, Italy had 186,108 new dementias (123,885 women) and 94,074 new strokes (53,572 women). Women had 98% higher crude dementia and 24% higher crude stroke burdens than men. The average age-standardized new dementia rate was 114.7 per 100,000 women and 88.4 per 100,000 men, both higher than Western Europe, the European Union, high-income countries, and the world. During 1990-2019, this rate increased in both sexes (4%), despite a decline in stroke (- 45%) and IHD (- 17%) in Italy. Dementia burden attributable to tobacco decreased in both sexes (- 12.7%) during 1990-2019, while high blood glucose and high body mass index combined burden increased (25.4%). Stroke and IHD had similar trends. CONCLUSIONS: While decreases in new strokes and IHDs are encouraging, new approaches to their joint prevention are required to reverse the rising dementia trends, especially among women. Life course approaches to promoting holistic brain health should be implemented at the community, national, and international levels before the growing trends become overwhelming.

Brain health and mental health: Common vascular risk factors and practical implications.

The pandemic dramatized the close links among cognitive, mental, and social health; a change in one reflects others. This realization offers the opportunity to bridge the artificial separation of brain and mental health, as brain disorders have behavioral consequences and behavioral disorders affect the brain. The leading causes of mortality and disability, namely stroke, heart disease, and dementia, share the same risk and protective factors. It is emerging that bipolar disorders, obsessive compulsive disorders, and some depressions share these risk factors, allowing their joint prevention through a holistic life span approach. We need to learn to focus on the whole patient, not simply on a dysfunctional organ or behavior to mitigate or prevent the major neurological and mental disorders by fostering an integrated approach to brain and mental health and addressing the common, treatable risk factors.

Integral brain health: Cerebral/mental/social provisional definitions.

Brain health matters to everyone, we all need to know what it is. The digital age, the knowledge-based society, and expanding virtual worlds require greater cognitive capacity and mental and social resilience to function and to contribute; and yet there are no agreed definitions for brain, mental, or social health. Moreover, no definition encompasses all three or recognizes their integrated, interactive nature. Such a definition would: Help integrate relevant facts lingering behind specialized definitions and jargons. Promote a more holistic approach to patients. Create synergies among disciplines. The new definition would come in three versions: A lay, a scientific, and a customized one depending on the purpose, for example, research, education, policy, and so forth. Buttressed by evolving evidence integrated and update through a Brainpedia, they would focus attention on the greatest investment that individuals and society can make: Integral brain health: Cerebral/mental/social, in a safe, healthy, and supportive environment.

Vitamin B 12 deficiency and hyperhomocysteinaemia in outpatients with stroke or transient ischaemic attack: a cohort study at an academic medical centre.

OBJECTIVE: We sought to assess the current magnitude of the opportunity for secondary stroke prevention with B vitamins. DESIGN: A cohort study. SETTING: The Urgent TIA (Transient Ischaemic Attack) Clinic at an academic medical centre. MAIN OUTCOME MEASURES: We assessed the prevalence of biochemical vitamin B12 deficiency (B12Def, serum B12 <156 pmol/L), hyperhomocysteinaemia (HHcy; plasma total homocysteine [tHcy] >14 µmol/L) and metabolic B12 deficiency (MetB12Def, serum B12 <258 pmol/L and HHcy) between 2002 and 2017, by age group and by stroke subtype. RESULTS: Data were available in 4055 patients. B12Def was present in 8.2% of patients overall; it declined from 10.9% of patients referred before 2009 to 5.4% thereafter (p=0.0001). MetB12Def was present in 10.6% of patients, and HHcy was present in 19.1% of patients. Among the patients aged ≥80 years, MetB12Def was present in 18.1% and HHcy in 35%. Among the 3410 patients whose stroke subtype was determined, HHcy was present in 18.4% of patients: 23.3% of large artery atherosclerosis, 18.1% of cardioembolic, 16.3% of small vessel disease, 10.8% of other unusual aetiologies and 13.6% of undetermined subtypes (p=0.0001). CONCLUSIONS: Despite a decline in our referral area since 2009, B12Def, MetB12Def and HHcy remain common in patients with stroke/TIA. Because these conditions are easily treated and have serious consequences, all patients with stroke/TIA should have their serum B12 and tHcy measured.

Anticoagulation Therapy for Atrial Fibrillation in Patients With Alzheimer's Disease.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

Vitamin D and caudal primary motor cortex: a magnetic resonance spectroscopy study.

BACKGROUND: Vitamin D is involved in brain physiology and lower-extremity function. We investigated spectroscopy in a cohort of older adults to explore the hypothesis that lower vitamin D status was associated with impaired neuronal function in caudal primary motor cortex (cPMC) measured by proton magnetic resonance spectroscopic imaging. METHODS: Twenty Caucasian community-dwellers (mean±standard deviation, 74.6±6.2 years; 35.0% female) from the 'Gait and Brain Study' were included in this analysis. Ratio of N-acetyl-aspartate to creatine (NAA/Cr), a marker of neuronal function, was calculated in cPMC. Participants were categorized according to mean NAA/Cr. Lower vitamin D status was defined as serum 25-hydroxyvitamin D (25OHD) concentration <75 nmol/L. Age, gender, number of comorbidities, vascular risk, cognition, gait performance, vitamin D supplements, undernourishment, cPMC thickness, white matter hyperintensities grade, serum parathyroid hormone concentration, and season of evaluation were used as potential confounders. RESULTS: Compared to participants with high NAA/Cr (n = 11), those with low NAA/Cr (i.e., reduced neuronal function) had lower serum 25OHD concentration (P = 0.044) and more frequently lower vitamin D status (P = 0.038). Lower vitamin D status was cross-sectionally associated with a decrease in NAA/Cr after adjustment for clinical characteristics (ß = -0.41, P = 0.047), neuroimaging measures (ß = -0.47, P = 0.032) and serum measures (ß = -0.45, P = 0.046). CONCLUSIONS: Lower vitamin D status was associated with reduced neuronal function in cPMC. These novel findings need to be replicated in larger and preferably longitudinal cohorts. They contribute to explain the pathophysiology of gait disorders in older adults with lower vitamin D status, and provide a scientific base for vitamin D replacement trials.

Thalamic cramplike pain.

IMPORTANCE: We describe a case of cramplike pain after a left thalamic ischemic stroke, a neglected type of central post-stroke pain and we describe its neuroanatomical correlates. OBSERVATIONS: A 68-year-old right-handed man presented with right arm, leg, and flank cramplike pain noted upon awakening. Neurological examination was normal, with no evidence of objective sensory abnormalities. Because of the nature of the pain and the preserved sensory function, we first did not consider stroke as a potential cause, and suspected that pain was related to the combined effect of intense physical exercising on the right side and the use of statins. Diffusion-weighted magnetic resonance imaging showed an acute ischemic infarction within the left thalamus. By registering high-resolution 3 T T1-weighted and T2-weighted magnetic resonance images to the Talairach atlas, we showed the infarction is within the border between the pulvinar and the ventral posterior medial nuclei. Brodmann's areas 3, 1, 2, 4 and 6 were identified as the cortical correlates of the ischemic lesion by diffusion tensor tractography. CONCLUSIONS AND RELEVANCE: Thalamic cramplike pain should be recognized as a type of central post-stroke pain, probably produced by lesions localized to the border between the ventral posterior and pulvinar nuclei and connected to the ipsilateral primary somatosensory cortex and primary and secondary motor cortices.

Motor cortex and gait in mild cognitive impairment: a magnetic resonance spectroscopy and volumetric imaging study.

Gait disorders are common in the course of dementia, even at the stage of mild cognitive impairment, owing to probable changes in higher levels of motor control. Since motor control message is ultimately supported in the brain by the primary motor cortex and since cortical lesions are frequent in the dementia process, we hypothesized that impairments of the primary motor cortex may explain the early gait disorders observed in mild cognitive impairment. Our purpose was to determine whether the neurochemistry of the primary motor cortex measured with proton magnetic resonance spectroscopy, and its volume, were associated with gait performance while single and dual-tasking in mild cognitive impairment. Twenty community dwellers with mild cognitive impairment, aged 76 years (11) [median (interquartile range)] (30% female) from the 'Gait and Brain Study' were included in this analysis. Gait velocity and stride time variability were measured while single (i.e. walking alone) and dual tasking (i.e. walking while counting backwards by seven) using an electronic walkway (GAITRite System). Ratios of N-acetyl aspartate to creatine and choline to creatine and cortical volume were calculated in the primary motor cortex. Participants were categorized according to median N-acetyl aspartate to creatine and choline to creatine ratios. Age, gender, body mass index, cognition, education level and subcortical vascular burden were used as potential confounders. Participants with low N-acetyl aspartate to creatine (n = 10) had higher (worse) stride time variability while dual tasking than those with high N-acetyl aspartate to creatine (P = 0.007). Those with high choline to creatine had slower (worse) gait velocity while single (P = 0.015) and dual tasking (P = 0.002). Low N-acetyl aspartate to creatine was associated with increased stride time variability while dual tasking (adjusted ß = 5.51, P = 0.031). High choline to creatine was associated with slower gait velocity while single (adjusted ß = -26.56, P = 0.009) and dual tasking (adjusted ß = -41.92, P = 0.022). Cortical volume correlated with faster gait velocity while single (P = 0.029) and dual tasking (P = 0.037), and with decreased stride time variability while single tasking (P = 0.034). Finally, the probability of exhibiting abnormal metabolite ratios in the primary motor cortex was 63% higher among participants with major gait disturbances in dual task. Those with compromised gait velocity in dual task had a 2.05-fold greater risk of having a smaller cortical volume. In conclusion, the neurochemistry and volume of the primary motor cortex were associated with gait performance while single and dual tasking. Stride time variability was mainly sensitive to neuronal function (N-acetyl aspartate to creatine), whereas gait velocity was more affected by inflammatory damage (choline to creatine) and volumetric changes. These findings may contribute to a better understanding of the higher risks of mobility decline and falls in subjects with mild cognitive impairment.

Escalating levels of access to in-hospital care and stroke mortality.

BACKGROUND AND PURPOSE: Organized stroke care is an integrated approach to managing stroke to improve stroke outcomes by ensuring that optimal treatment is offered. However, limited information is available comparing different levels of organized care. Our aim was to determine whether escalating levels of organized care can improve stroke outcomes. METHODS: Cohort study including patients with acute ischemic stroke between July 2003 and March 2005 in the Registry of the Canadian Stroke Network (RCSN). The RCSN is the largest clinical database of patients with acute stroke patients seen at selected acute care hospitals in Canada. As stroke unit admission does not automatically imply receipt of comprehensive care, we created the organized care index to represent different levels of access to organized care ranging from 0 to 3 as determined by the presence of occupational therapy/physiotherapy, stroke team assessment, and admission to a stroke unit. The primary end point was early stroke mortality. Secondary end points include 30-day and 1-year mortality. RESULTS: Overall, 3631 ischemic stroke patients were admitted to 11 hospitals. Seven day stroke mortality was 6.9% (249/3631), 30-day stroke mortality was 12.6% (457/3631), and 1-year stroke mortality was 23.6% (856/3631). Risk-adjusted 7-day mortality was 2.0%, 3.2%, 7.8%, and 22.5% for organized care index of 3, 2, 1, and 0. Higher level of care was associated with lower adjusted mortality (for organized care index 3, OR 0.03, 95% CI 0.02 to 0.07 for 7-day mortality; OR 0.09, 95% CI 0.05 to 0.17 for 30-day mortality; and OR 0.40, 95% CI 0.25 to 0.64 for 1-year mortality). CONCLUSIONS: Higher level of access to care was associated with lower stroke mortality rates. Establishing a well-organized and multidisciplinary system of stroke care will help improve the quality of service delivered and reduce the burden of stroke.