Cardiovascular Risk Factors and Risk of Alzheimer Disease and Mortality: A Latent Class Approach

BackgroundCardiovascular risk factors co‐occur with one another, and little is known about the extent of their clustering and risk of Alzheimer disease (AD). We identify groups of cardiovascular risk factors in cognitively normal individuals and investigate between‐group differences in incident AD and death.Methods and ResultsCognitively normal individuals were recruited from the National Alzheimer's Coordinator Center. A latent class analysis was conducted with hypertension, hypercholesterolemia, heart condition, stroke, smoking history, diabetes, and high body mass index. Between‐group differences in the incidence of AD, mortality, and mortality‐adjusted AD were investigated. This study included 12 412 cognitively normal individuals (average follow‐up, 65 months). Three groups were identified: (1) low probabilities of cardiovascular risk factors (reference; N=5398 [43%]), (2) hypertension and hypercholesterolemia (vascular‐dominant; N=5721 [46%]), and (3) hypertension, hypercholesterolemia, diabetes, and high body mass index (vascular‐metabolic; N=1293 [10%]). Both vascular groups were significantly older, had more men, were slightly less educated, and were slightly more cognitively impaired than the reference group (all P<0.05). However, only the vascular‐metabolic group had a significantly younger age of death compared with the reference group (84.3 versus 88.7 years, P<0.001). Only the vascular‐dominant group had a greater incidence of AD (odds ratio [OR], 1.30; P<0.001) compared with the reference group. Mortality was greater in the vascular‐dominant (OR, 3.26; P<0.001) and vascular‐metabolic groups (OR, 1.84; P=0.02). Mortality‐adjusted AD was greater in the vascular‐dominant (OR, 1.54; P=0.02) and vascular‐metabolic groups (OR, 1.46; P=0.04).ConclusionsThree distinct cardiovascular risk factor groups were identified in cognitively normal elderly individuals. Only the vascular‐dominant group was associated with a greater incidence of AD. Selective mortality may contribute to the attenuated association between the vascular‐metabolic group and incident AD.publishedVersio

Agitation in cognitive disorders: Progress in the International Psychogeriatric Association consensus clinical and research definition

Background: The International Psychogeriatric Association (IPA) published a provisional consensus definition of agitation in cognitive disorders in 2015. As proposed by the original work group, we summarize the use and validation of criteria in order to remove "provisional" from the definition. Methods: This report summarizes information from the academic literature, research resources, clinical guidelines, expert surveys, and patient and family advocates on the experience of use of the IPA definition. The information was reviewed by a working group of topic experts to create a finalized definition. Results: We present a final definition which closely resembles the provisional definition with modifications to address special circumstances. We also summarize the development of tools for diagnosis and assessment of agitation and propose strategies for dissemination and integration into precision diagnosis and agitation interventions. Conclusion: The IPA definition of agitation captures a common and important entity that is recognized by many stakeholders. Dissemination of the definition will permit broader detection and can advance research and best practices for care of patients with agitation.publishedVersio

Perspectives on ethnic and racial disparities in Alzheimer\u27s disease and related dementias: Update and areas of immediate need

Alzheimer\u27s disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer\u27s Association International Society to Advance Alzheimer\u27s Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise “state-of-the-science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations. © 2018 The Author

Centre- versus home-based exercise among people with mci and mild dementia: study protocol for a randomized parallel-group trial

Abstract Background Worldwide, almost 50million people lived with dementia in 2016. A cure or disease modifying pharmaceutical treatment for dementia remains elusive so alternative therapies are of critical importance. Mounting evidence supports exercise in the prevention and therapy of dementia. However, the cognitive, physical, and psychological challenges common to dementia along with a poor understanding and accommodation of dementia in the community are major barriers to exercise. Consequently, effective delivery options need to be identified. The primary objective of this study is to compare the effectiveness of center-based (CB) exercise versus home-based (HB) exercise for achievement of physical activity guidelines among people with MCI or mild dementia. Methods This is a randomized parallel-group trial comparing the effects of CB and HB exercise adherence among community-dwelling adults ≥50 years with a clinical diagnosis of MCI or mild dementia. Participants will be randomized to either CB or HB exercise. The CB group will meet weekly for small group exercise and will be prescribed additional exercise to be completed independently. Participants in the HB group will be given a physical activity prescription to be completed independently in the community. Participants in HB will also be contacted by phone monthly to adjust exercise prescriptions. The primary outcome will be achievement of exercise guidelines (150 min/wk. of moderate activity) assessed using an activity monitor. Secondary objectives will evaluate cost-effectiveness and the influence of individual and environmental factors on the primary outcome. Tertiary outcomes include physical function, cognition, mood, and quality of life. Discussion There is scant research to indicate the most effective way to deliver exercise to people with MCI and mild dementia, which is needed specifically because these groups face significant barriers to exercise. To capitalize on the benefits of exercise, feasible exercise delivery options need to be identified. The results of this study will directly complement ongoing clinical trials and will be essential to implementing exercise recommendations specific to the prevention and therapy of dementia in a feasible and cost-effective manner when they emerge. Trial registration. Clinicatrials.gov; Identifier: NCT02774720 (version updated December 12, 2016)

Treatment effects in multiple cognitive domains in Alzheimer’s disease: a two-year cohort study

Abstract Introduction Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer’s disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort. Methods A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE). Results At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function. Conclusions The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system

Apathy as a Treatment Target in Alzheimer&apos;s Disease: Implications for Clinical Trials

Apathy is one of the most prevalent, stable and persistent neuropsychiatric symptom across the neurocognitive disorders spectrum. Recent advances in understanding of phenomenology, neurobiology and intervention trials highlight apathy as an important target for clinical intervention. We conducted a comprehensive review and critical evaluation of recent advances to determine the evidence-based suggestions for future trial designs. This review focused on 4 key areas: 1) pre-dementia states; 2) assessment; 3) mechanisms/biomarkers and 4) treatment/intervention efficacy. Considerable progress has been made in understanding apathy as a treatment target and appreciating pharmacological and non-pharmacological apathy treatment interventions. Areas requiring greater investigation include: diagnostic procedures, symptom measurement, understanding the biological mechanisms/biomarkers of apathy, and a well formed approach to the development of treatment strategies. A better under- standing of the subdomains and biological mechanisms of apathy will advance apathy as a treatment target for clinical trials. (Am J Geriatr Psychiatry 2022; 30:119-147

Criteria for Psychosis in Major and Mild Neurocognitive Disorders: International Psychogeriatric Association (IPA) Consensus Clinical and Research Definition.

Psychosis is common among individuals with neurocognitive disorders, is difficult to manage, and causes considerable burden and stress to patients and caregivers. Developing effective treatments is a substantial unmet medical need but research has been slowed by the need for updated consensus diagnostic criteria. To address this need, the International Psychogeriatrics Association initiated a process to develop criteria for clinical use, research, and treatment development efforts. The process included clinical, regulatory, and industry stakeholders as well as input from a global network of experts in geriatric psychiatry responding to two surveys (N = 336). Results from the consensus process confirmed that clinicians wanted elaboration of aspects of the definition proposed by Jeste and Finkel in 2000 to ensure that the criteria are applied appropriately. Based on discussions, the survey, and emerging research, criteria were revised to apply to psychosis occurring with all major and mild neurocognitive disorders. Other important changes include providing examples of hallucinations and delusions and clarifying time course, impact, and exclusionary criteria. This definition of psychosis in major and mild neurocognitive disorders can be used to advance many types of research including development of much needed pharmacologic and nonpharmacologic interventions for psychosis in patients with neurocognitive disorders