Journal of Alzheimer's Disease - Volume 42, issue s4

Authors: Thal, Dietmar Rudolf | Attems, Johannes | Ewers, Michael

Article Type: Research Article

Abstract: Primary pathologies including amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT) develop many years before the onset of dementia symptoms in Alzheimer's disease (AD). Age-related small vessel disease (SVD) is common in elderly subjects and may contribute to the clinical syndrome of AD. Each type of pathology shows a specific spatio-temporal sequence of spreading in the brain. Here, we review neuropathological and neuroimaging findings (PET tracers of Aβ and NFT, MRI markers of SVD) to assess whether staging of these primary pathologies is useful to predict clinical symptoms in AD. On the basis of neuropathological data, early stages of Aβ plaque …and NFT pathology distribution occur in preclinical AD, but advanced stages with spreading into further brain regions are associated with dementia symptoms. Amyloid PET presumably detects Aβ in advanced neuropathological Aβ stages, and increased global amyloid PET uptake is associated with clinical worsening in non-demented subjects. Tau PET may provide additional predictive value by detecting NFT in the allocortex. There is weak evidence that SVD is related to amyloid or NFT pathology. Global volume of MRI-assessed white matter hyperintensities (WMH) contribute in addition to biomarker levels of Aβ to predict cognitive decline. Regional differences of the effect of WMH on cognition have been demonstrated but are not yet established as a biomarker in AD. In conclusion, biomarkers for amyloid and tau pathology allow a distinction between early and advanced stages of AD, but a subgroup of pathologically identified preclinical AD cases is not identified by the currently available biomarkers. Show more

Keywords: Alzheimer's disease, amyloid-β, biomarker, diagnosis, early detection, magnetic resonance imaging, neurofibrillary tangles, plaques, positron emission tomography, small vessel disease

DOI: 10.3233/JAD-141461

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S421-S429, 2014

Authors: de la Torre, Jack C.

Article Type: Review Article

Abstract: The incidence rate in Alzheimer's disease (AD) is expected to quadruple worldwide by 2050. To limit this impending socio-medical calamity, a fulcrum change from how AD is presently managed is crucial. The present approach has not averted the stress of AD on medical resources nor reduced the already cost-strained government health care programs. Since substantial evidence indicates that sporadic AD is directly associated with vascular risk factors, a strategic plan is proposed to target this association and markedly reduce the onset of AD. This plan would establish in-house heart-brain clinics devoted to identifying, detecting, and preventing the progression of vascular …risk factors that predispose to cognitive impairment and development of AD. The heart-brain clinics would be staffed with a multidisciplinary group of neurologists, psychologists, neuroradiologists, cardiovascular specialists, and technical personnel Their goal would be to apply and interpret non-invasive, cost-effective multidiagnostic testing of heart and brain function in outpatient asymptomatic and symptomatic patients at risk of dementia. Multidiagnostic testing would permit better risk stratification, medical decision-making, and a tailored intervention of patients at-risk of dementia than the present monotherapeutic approach. Personalized intervention, moreover, should achieve better patient compliance and outcome through periodic follow-up visits to the clinics where the medical plan of action could be monitored and modified as needed. Multidisciplinary heart-brain clinics will be costly at first but eventually should become cost-effective while providing an invaluable medical service to an aging population and possibly extending years of full-health lived in those at risk of dementia. Show more

Keywords: Alzheimer's disease, cognitive impairment, detection, heart-brain clinics, multidiagnostic testing, prevention, vascular risk factors

DOI: 10.3233/JAD-141560

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S431-S442, 2014

Authors: van Buchem, Mark A. | Biessels, Geert Jan | Brunner la Rocca, Hans Peter | de Craen, Anton J.M. | van der Flier, Wiesje M. | Ikram, M. Arfan | Kappelle, L. Jaap | Koudstaal, Peter J. | Mooijaart, Simon P. | Niessen, Wiro | van Oostenbrugge, Robert | de Roos, Albert | van Rossum, Albert C. | Daemen, Mat J.A.P.

Article Type: Review Article

Abstract: While both cardiac dysfunction and progressive loss of cognitive functioning are prominent features of an aging population, surprisingly few studies have addressed the link between heart and brain function. This is probably due to the monodisciplinary approach to these problems by cardiologists, neurologists, and geriatricians. Recent data indicate that autoregulation of cerebral flow cannot always protect the brain from hypoperfusion when cardiac output is reduced or atherosclerosis is prominent. This suggests a close link between cardiac function and large vessel atherosclerosis on the one hand and brain perfusion and cognitive functioning on the other. In a national research program, we …will test the hypothesis that impaired hemodynamic status of both heart and brain is an important and potentially reversible cause of vascular cognitive impairment (VCI) offering promising opportunities for treatment. Using a multidisciplinary approach, we will address the following questions: 1) To what extent do hemodynamic changes contribute to VCI? 2) What are the mechanisms involved? 3) Does improvement of the hemodynamic status lead to improvement of cognitive dysfunction? To this end we will perform clinical studies in elderly patients with clinically manifest VCI, carotid occlusive disease, or heart failure and evaluate their cardiac and large vascular function, atherosclerotic load, and cerebral perfusion with a comprehensive magnetic resonance imaging protocol and thoroughly test their cognitive function. We will also analyze epidemiological data from the Rotterdam Study. Show more

Keywords: Atherosclerosis, heart, magnetic resonance imaging, vascular cognitive impairment

DOI: 10.3233/JAD-141542

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S443-S451, 2014

Authors: Poggesi, Anna | Salvadori, Emilia | Valenti, Raffaella | Nannucci, Serena | Ciolli, Laura | Pescini, Francesca | Pasi, Marco | Fierini, Fabio | Donnini, Ida | Marini, Sandro | Chiti, Guido | Rinnoci, Valentina | Inzitari, Domenico | Pantoni, Leonardo

Article Type: Research Article

Abstract: Background and objective: Services dedicated to patients with cognitive and behavioral consequences of cerebrovascular diseases are not well established. In this paper, we report on the general organization of such a service (the Florence VAS-COG Clinic) after 9 years of activity, updating a previous work related to the first 5 years. Methods: The Florence VAS-COG clinic, started in 2006, is an outpatient service dedicated to the assessment and follow-up of patients with cerebrovascular diseases and related cognitive, psychiatric, and behavioral disturbances. The staff involved in the clinic is composed of certified neurologists, one neuropsychologist, and neurology residents. The …diagnostic protocol includes detailed personal and family history, general and neurologic examinations, and functional, neuropsychological, and neuroimaging assessment. After this work-up, comprehensive diagnoses are made. Results: From January 2006 to March 2014, 600 patients (mean age 67.3 years ± 13.9; 52% females) have been evaluated in the clinic. Cognitive impairment, including mild cognitive impairment and dementia, mainly of vascular origin, was the most common (36.4%) diagnostic category, followed by suspected or confirmed familial micro-angiopathy (35.8%). Compared to the first years of activity, we are now facing the need of augmenting the number of visits due to increasing request and to better implement the multidisciplinarity of the team. Efforts are currently directed towards the definition of management protocols in pharmacological and non-pharmacological strategies. Conclusions: The establishment of a VAS-COG clinic represents an important step for the appreciation of the patient clinical needs and for the implementation of screening, diagnostic, and treatment options in the field of the neuropsychiatric consequences of cerebrovascular diseases. Show more

Keywords: Dementia, mild cognitive impairment, outpatient clinic, post-stroke aphasia, post-stroke depression, small vessel disease, stroke, vascular cognitive impairment

DOI: 10.3233/JAD-141569

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S453-S461, 2014

Authors: Anstey, Kaarin J. | Eramudugolla, Ranmalee | Dixon, Roger A.

Article Type: Review Article

Abstract: The development and integration of risk assessment and clinical risk management for Alzheimer's disease (AD) and dementia is a rapidly emerging field of research and practice. At present, risk management is the only available approach with potential for a large impact on the projected rates of dementia, given population aging. This review describes six available risk assessment tools, including those developed specifically for AD and those for dementia. These tools differ along several important dimensions, including whether they (a) include clinical measures, (b) require a clinician's ratings, (c) are predominantly self-report, (d) are independently validated, and (e) are available online. …A narrative review of recently identified risk factors not included in these instruments is included, indicating future directions for risk assessment. Finally, consideration is given to the prioritization of risk advice according to the ease of risk modification and the potential for synergies among risk factors. Show more

Keywords: Alzheimer's disease, cognitive decline, prevention, risk assessment, risk factor

DOI: 10.3233/JAD-141248

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S463-S473, 2014

Authors: Polidori, Maria Cristina

Article Type: Review Article

Abstract: Malnutrition-, obesity-, and Alzheimer's disease (AD)-related burden to patients and society are among the main public health challenges of our time in both developed and developing countries. Poor nutrition as part of an unhealthy lifestyle is one of the modifiable risk factors for AD, and its improvement has been the recent focus of several interventional and epidemiologic studies. There is an impressive body of evidence supporting the beneficial role of balanced nutrition in lowering the risk of dementia, but despite worldwide dementia epidemics, lack of information still leads to (too) late diagnosis and (symptomatic) interventions. The aim of this work …is to critically summarize knowledge on the preventive effects of natural nutrition against AD onset and to present a multidimensional and individualized approach aimed at delaying AD onset in community dwellers with subjective and mild cognitive complaints. Show more

Keywords: Alzheimer's disease, antioxidant, clinical trial, counseling, mild cognitive impairment, natural nutrition, oxidative stress

DOI: 10.3233/JAD-141539

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S475-S482, 2014

Authors: Hampstead, Benjamin M. | Mosti, Caterina B. | Swirsky-Sacchetti, Thomas

Article Type: Review Article

Abstract: Projections indicate that the prevalence of Alzheimer's disease (AD) and other dementias will increase two to three fold in the coming decades. As a result, there has been considerable interest in identifying methods that maintain or enhance cognitive functioning in these older adults. Existing pharmacological agents are limited in this respect and disease-modifying agents are years away from being available. Cognitively based interventions (i.e., cognitive training, cognitive rehabilitation) hold particular promise for maximizing patients' functioning, are relatively inexpensive, and have virtually no side effects. Everyday life is complex and multifaceted, which means that a personalized approach is essential for maximizing …and prolonging functioning in each patient. Unfortunately, little is known about the factors contributing to such an approach. The current review first identifies several lifestyle factors that have been shown to be neuroprotective as well as risk factors that may ultimately contribute to the efficacy of different cognitive intervention techniques. There is a critical need to understand the conditions under which individual techniques are effective; an issue examined through characteristic examples across the AD spectrum. While limited at this time, there is some evidence of the long-term benefits of cognitive intervention. We conclude by describing several critical areas of investigation and proposing a clinically oriented framework for both furthering cognitive intervention research and providing patient-centered care. Show more

Keywords: Aging, biomarker, cognitive rehabilitation, cognitive training, learning, memory, mild cognitive impairment

DOI: 10.3233/JAD-141476

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S483-S493, 2014

Authors: Wang, Ze

Article Type: Review Article

Abstract: Searching for biomarkers sensitive to early Alzheimer's disease (AD) and its progression has been a research priority for two decades. MRI has been increasingly used for this endeavor because of its capability of detecting both structural and functional brain patterns without injecting external contrast agent or radioactive tracers. Recent work has shown sensitivity of hippocampal volume and regional cerebral blood flow for differentiating prodromal AD from normal controls as well as AD. This review provides a summary for the existing literature describing the applications of either or both modalities in early AD studies as well as disease progression assessment. The …various findings in the reviewed studies lead to a conclusion of assessing hippocampal volume and arterial spin labeling cerebral blood flow as potential markers for disease detection, and progression monitoring though longitudinal studies are still lacking to fully examine their sensitivity and specificity. Show more

Keywords: Arterial spin labeling, cerebral blood flow, diagnosis, grey matter volume, hippocampus, imaging

DOI: 10.3233/JAD-141419

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S495-S502, 2014

Authors: Zeki Al Hazzouri, Adina | Yaffe, Kristine

Article Type: Review Article

Abstract: Cognitive decline and dementia are a major cause of disability and mortality among older adults. Cross-sectional evidence from observational studies suggests that greater arterial stiffness is associated with worse cognitive performance. These associations have been observed on measures of global cognition and across multiple domains of cognition. Epidemiologic evidence on the association between arterial stiffness and rate of cognitive decline has been less definitive, and very few studies have investigated the risk of developing dementia. This review summarizes the current research on arterial stiffness and cognition, issues around measurement, and the effect that potential intervention might have on the course …of cognitive aging. The evidence on pharmacological and non-pharmacological (exercise, nutrition, etc.) interventions in older adults with arterial stiffness is promising. Yet there are no studies or trials that directly evaluate how interventions of arterial stiffness reduce or prevent cognitive impairment and risk of developing dementia. More research is needed to elucidate the causal link between arterial stiffness and cognitive decline and dementia, and to identify whether potential interventions to prevent or reduce arterial stiffness may benefit cognitive health of the elderly. Show more

Keywords: Aging, arterial stiffness, cognitive decline, dementia, epidemiology

DOI: 10.3233/JAD-141563

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S503-S514, 2014

Authors: Rodríguez-Gómez, Octavio | Palacio-Lacambra, M. Eugenia | Palasí, Antoni | Ruiz-Laza, Agustín | Boada-Rovira, Mercè

Article Type: Review Article

Abstract: The incidence of dementia is rapidly increasing in developed countries due to social and demographic changes. This trend is expected to worsen in the coming decades, with the number of cases possibly even tripling in the next 25 years. Therefore Alzheimer's disease (AD) prevention is becoming a global health priority. Our knowledge of the pathophysiological process leading to the development of pathological brain lesions that characterize AD has increased exponentially in recent years. However, the phenotypic expression of AD not only depends on the development of senile plaques and neurofibrillary tangles but other factors also play a role. Thus, over …the last few decades, epidemiological studies have revealed several risk factors for developing AD, such as vascular or lifestyle related factors. Having the current knowledge on AD, two different strategies have been developed for the prevention of AD: one is based on primary prevention by acting on modifiable risk factors, the other is a pathophysiology-driven approach aimed to identify individuals in a preclinical stage of the disease and treating them with drugs purporting to act on molecular targets of the amyloid cascade. Several promising trials with these approaches are currently ongoing and results are expected in the next few years. The intrinsic limitations in the design of preventive trials should be overcome through a global effort involving healthy population, healthcare professionals, governments, industry, and scientific institutions. This exertion will be more than compensated if we can make AD a preventable disease. Show more

Keywords: Alzheimer's disease, anti-amyloid therapy, multidomain approach, preclinical Alzheimer's disease, preventive clinical trials, primary prevention, secondary prevention, vascular risk factors

DOI: 10.3233/JAD-141479

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S515-S523, 2014