scholarly journals Multimodal Preventive Trial for Alzheimer’s Disease: MIND-ADmini Pilot Trial Study Design and Progress

Author(s):  
S. Sindi ◽  
C. Thunborg ◽  
A. Rosenberg ◽  
P. Andersen ◽  
S. Andrieu ◽  
...  

Background: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer’s disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. Objectives: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. Methods: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. Results: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. Conclusions: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).

2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tadeja Gracner ◽  
Patricia W. Stone ◽  
Mansi Agarwal ◽  
Mark Sorbero ◽  
Susan L Mitchell ◽  
...  

Abstract Background Though work has been done studying nursing home (NH) residents with either advanced Alzheimer’s disease (AD) or Alzheimer’s disease related dementia (ADRD), none have distinguished between them; even though their clinical features affecting survival are different. In this study, we compared mortality risk factors and survival between NH residents with advanced AD and those with advanced ADRD. Methods This is a retrospective observational study, in which we examined a sample of 34,493 U.S. NH residents aged 65 and over in the Minimum Data Set (2011–2013). Incident assessment of advanced disease was defined as the first MDS assessment with severe cognitive impairment (Cognitive Functional Score equals to 4) and diagnoses of AD or ADRD. Demographics, functional limitations, and comorbidities were evaluated as mortality risk factors using Cox models. Survival was characterized with Kaplan-Maier functions. Results Of those with advanced cognitive impairment, 35 % had AD and 65 % ADRD. At the incident assessment of advanced disease, those with AD had better health compared to those with ADRD. Mortality risk factors were similar between groups (shortness of breath, difficulties eating, substantial weight-loss, diabetes mellitus, heart failure, chronic obstructive pulmonary disease, and pneumonia; all p < 0.01). However, stroke and difficulty with transfer (for women) were significant mortality risk factors only for those with advanced AD. Urinary tract infection, and hypertension (for women) only were mortality risk factors for those with advanced ADRD. Median survival was significantly shorter for the advanced ADRD group (194 days) compared to the advanced AD group (300 days). Conclusions There were distinct mortality and survival patterns of NH residents with advanced AD and ADRD. This may help with care planning decisions regarding therapeutic and palliative care.


2020 ◽  
Vol 29 (8) ◽  
pp. 460-469 ◽  
Author(s):  
Kevin Hope

A multidisciplinary advisory group of health professionals involved in dementia care assessed the current evidence base regarding modifiable risk factors (MRFs) for early Alzheimer's disease and mild cognitive impairment. Based on evidence from the published literature and clinical experience, MRFs in four areas were identified where there is evidence to support interventions that may help delay cognitive decline or reduce the risk of developing Alzheimer's disease: medical (eg cardiovascular risk factors), psychosocial (eg depression, anxiety, social isolation), lifestyle (eg lack of physical activity, smoking) and nutrition (eg poor diet, lack of micronutrients). Practical guidance on how health professionals, but in particular nurses, may actively seek to address these MRFs in clinical practice was also developed. Nurses are at the forefront of patient care and, as such, are ideally placed to offer advice to patients that may proactively help mitigate the risks of cognitive decline and the development of Alzheimer's disease.


2001 ◽  
Vol 86 (3) ◽  
pp. 313-321 ◽  
Author(s):  
M. González-Gross ◽  
Ascensión Marcos ◽  
Klaus Pietrzik

As the number of older people is growing rapidly worldwide and the fact that elderly people are also apparently living longer, dementia, the most common cause of cognitive impairment is getting to be a greater public health problem. Nutrition plays a role in the ageing process, but there is still a lack of knowledge about nutrition-related risk factors in cognitive impairment. Research in this area has been intensive during the last decade, and results indicate that subclinical deficiency in essential nutrients (antioxidants such as vitamins C, E and β-carotene, vitamin B12, vitamin B6, folate) and nutrition-related disorders, as hypercholesterolaemia, hypertriacylglycerolaemia, hypertension, and diabetes could be some of the nutrition-related risk factors, which can be present for a long time before cognitive impairment becomes evident. Large-scale clinical trials in high-risk populations are needed to determine whether lowering blood homocysteine levels reduces the risk of cognitive impairment and may delay the clinical onset of dementia and perhaps of Alzheimer's disease. A curative treatment of cognitive impairment, especially Alzheimer's disease, is currently impossible. Actual drug therapy, if started early enough, may slow down the progression of the disease. Longitudinal studies are required in order to establish the possible link of nutrient intake – nutritional status with cognitive impairment, and if it is possible, in fact, to inhibit or delay the onset of dementia.


2016 ◽  
Vol 37 (5) ◽  
pp. 545-569 ◽  
Author(s):  
Karen I. Fredriksen-Goldsen ◽  
Sarah Jen ◽  
Amanda E. B. Bryan ◽  
Jayn Goldsen

Cognitive impairment, Alzheimer’s disease, and other dementias are important health concerns for older adults. As a marginalized and growing segment of the older adult population, lesbian, gay, bisexual, and transgender (LGBT) older adults face distinct risk factors related to cognitive impairment and dementias, including social isolation, discrimination, barriers to health care access, limited availability of and support for caregivers, and higher rates of certain chronic illnesses. We examine cognitive impairment and dementias among LGBT older adults, describe their unique risk factors, and outline key competencies for health care and human service providers to ensure culturally relevant care for LGBT older adults experiencing cognitive impairment, Alzheimer’s disease, or other dementias, as well as their caregivers, families, and communities. Implications include developing an awareness of the context of LGBT older adults’ lives and relationships, the importance of early detection and support, and the development of policies and practices that promote community-level advocacy and education.


2013 ◽  
Vol 26 (1) ◽  
pp. 7-7 ◽  
Author(s):  
Nicola T. Lautenschlager

With the global aging of our societies and predicted increase of cognitive impairment and dementia, it is no surprise that there is an increasing interest in the research community, but also among clinicians and the general population to learn more about how to focus on modifiable protective factors and how to avoid modifiable risk factors. A recent review of systematic reviews and meta-analyses on significant risk factors for Alzheimer's disease (AD) highlighted the importance of diabetes, hypertension, obesity, smoking, depression, cognitive inactivity, and physical inactivity (Barnes and Yaffe, 2011). For physical inactivity, for example, the authors reported that up to one million cases of AD could be prevented globally if a physical inactivity could be reduced by 25%. However, we should not forget about the various stages of prevention, and especially in the field of psychogeriatrics should also ask what preventative measures might be effective for older adults who have already experienced cognitive impairment. So we could focus on a secondary prevention approach for individuals with mild cognitive impairment (MCI) or on a tertiary preventative approach for patients with dementia. The number of randomized controlled trials (RCT) investigating the effectiveness of physical activity on cognition is limited for healthy participants and those with MCI, but is even more sparse for those with dementia. Even with the limited number of studies it often is difficult to compare RCTs due to the huge variation in inclusion and exclusion criteria, methodology, instruments used and outcomes, intervention and duration of interventions, and observations.


2021 ◽  
Vol 15 ◽  
Author(s):  
Angeles Vinuesa ◽  
Carlos Pomilio ◽  
Amal Gregosa ◽  
Melisa Bentivegna ◽  
Jessica Presa ◽  
...  

Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer’s disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wietse A. Wiels ◽  
Mandy M. J. Wittens ◽  
Dieter Zeeuws ◽  
Chris Baeken ◽  
Sebastiaan Engelborghs

Background: The interaction between neuropsychiatric symptoms, mild cognitive impairment (MCI), and dementia is complex and remains to be elucidated. An additive or multiplicative effect of neuropsychiatric symptoms such as apathy or depression on cognitive decline has been suggested. Unraveling these interactions may allow the development of better prevention and treatment strategies. In the absence of available treatments for neurodegeneration, a timely and adequate identification of neuropsychiatric symptom changes in cognitive decline is highly relevant and can help identify treatment targets.Methods: An existing memory clinic-based research database of 476 individuals with MCI and 978 individuals with dementia due to Alzheimer's disease (AD) was reanalyzed. Neuropsychiatric symptoms were assessed in a prospective fashion using a battery of neuropsychiatric assessment scales: Middelheim Frontality Score, Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD), Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia (CSDD), and Geriatric Depression Scale (30 items). We subtyped subjects suffering from dementia as mild, moderate, or severe according to their Mini-Mental State Examination (MMSE) score and compared neuropsychiatric scores across these groups. A group of 126 subjects suffering from AD with a significant cerebrovascular component was examined separately as well. We compared the prevalence, nature, and severity of neuropsychiatric symptoms between subgroups of patients with MCI and dementia due to AD in a cross-sectional analysis.Results: Affective and sleep-related symptoms are common in MCI and remain constant in prevalence and severity across dementia groups. Depressive symptoms as assessed by the CSDD further increase in severe dementia. Most other neuropsychiatric symptoms (such as agitation and activity disturbances) progress in parallel with severity of cognitive decline. There are no significant differences in neuropsychiatric symptoms when comparing “pure” AD to AD with a significant vascular component.Conclusion: Neuropsychiatric symptoms such as frontal lobe symptoms, psychosis, agitation, aggression, and activity disturbances increase as dementia progresses. Affective symptoms such as anxiety and depressive symptoms, however, are more frequent in MCI than mild dementia but otherwise remain stable throughout the cognitive spectrum, except for an increase in CSDD score in severe dementia. There is no difference in neuropsychiatric symptoms when comparing mixed dementia (defined here as AD + significant cerebrovascular disease) to pure AD.


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