Journal of Alzheimer's Disease - Volume 20, issue 3

Authors: Sofi, Francesco | Macchi, Claudio | Abbate, Rosanna | Gensini, Gian Franco | Casini, Alessandro

Article Type: Review Article

Abstract: Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized by cognitive and memory deterioration, with an increasing prevalence in the industrialized countries and an extraordinary cost of caring for patients. Due to the limited information available on the exact pathophysiology of the disease, over the last years there have been extensive efforts on the identification of possible risk factors, but no conclusive data have been obtained. Some risk factors have been identified but no clear evidence on what is clearly associated with the occurrence and progression of AD are available, and in particular no effective preventive strategies have …been found. One of the most intriguing and appealing lines of investigation is the association between lifestyle habits such as diet and dietary compounds and the occurrence of AD. In this review, we focus on studies that investigated the association between nutrition and AD, paying particular attention to the role of a dietary pattern such as a Mediterranean-like diet on the occurrence of such disease. Studies in support of Mediterranean diet as an optimal diet for prevention of cardiovascular and major chronic diseases has rapidly evolved. A recent meta-analysis from our group, comprising prospective studies that investigated the association between adherence to Mediterranean diet and health status, showed a significant association between a greater adherence to Mediterranean diet and a reduced risk of major chronic degenerative diseases, including AD. Moreover, the Mediterranean diet has been extensively reported to be associated with a favorable health outcome and a better quality of life. Show more

Keywords: Alzheimer's disease, health, Mediterranean diet, nutrition

DOI: 10.3233/JAD-2010-1418

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 795-801, 2010

Authors: Flicker, Leon

Article Type: Review Article

Abstract: There is increasing evidence that some lifestyle factors are linked to the development of Alzheimer's disease. Many of these are potentially modifiable and include smoking, physical activity, education, social engagement, cognitive stimulation, and diet. Modification of most of these factors has other health advantages, increasing the potential benefits of modifying the individual's lifestyle. Unfortunately, most of the current evidence is based on observational data, and where human trials have been performed they have used surrogate outcomes rather than the development of Alzheimer's disease. For many of these modifiable lifestyle factors, such trials may never be performed, and an individual's choice …may need to be based on the available evidence. Show more

Keywords: Alzheimer's disease, lifestyle, older people, prevention

DOI: 10.3233/JAD-2010-091624

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 803-811, 2010

Authors: Jefferson, Angela L.

Article Type: Review Article

Abstract: Heart failure has served as a clinically useful model for understanding how cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to clinical brain injury. This review summarizes more recent data suggesting that subtle cardiac dysfunction or low normal levels of cardiac function, as quantified by cardiac output, are related to cognitive and neuroimaging markers of abnormal brain aging in the absence of heart failure or severe cardiomyopathy. Additional work is required, but such associations suggest that reduced cardiac output may be a risk factor for Alzheimer's disease (AD) …and abnormal brain aging through the propagation or exacerbation of neurovascular processes, microembolism due to thrombosis, and AD neuropathological processes. Such mechanistic pathways are discussed in the context of a theoretical model that posits a direct pathway of injury between cardiac output and abnormal brain aging (i.e., reduced systemic blood flow disrupts cerebral blood flow homeostasis), contributing to clinical brain injury, independent of shared risk factors for both cardiac dysfunction and abnormal brain aging. Show more

Keywords: Alzheimer's disease, cardiac output, cardiovascular disease, cognition

DOI: 10.3233/JAD-2010-100081

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 813-821, 2010

Authors: Tierney, Mary C. | Lermer, Miriam A.

Article Type: Review Article

Abstract: The incidence and prevalence in those over age 65 of neurodegenerative disorders and chronic diseases, which often have deleterious effects on cognition, are rapidly increasing in western societies. Primary care physicians (PCPs) provide the majority of medical treatment for older people and in order to effectively care for their patients with suspected cognitive impairment, they must have tools that will allow them to accurately assess their patient's cognitive function. This knowledge will assist the PCPs in formulating a diagnosis of dementia or cognitive impairment and provide an indication of risk of progression to dementia. It will also assist with monitoring …response to treatment and care decisions, including medication management, capacity judgments, and the need for family involvement. Tests currently used in primary care, such as the Mini-Mental State Examination, do not accurately assess patients with mild cognitive impairments, and other tests more suitable for this purpose require further validation and may be too time-consuming in the primary care setting. A possible solution is the use of patient-administered computerized cognitive testing in the PCP's office. This systematic review identified eleven test batteries and three were judged potentially appropriate for cognitive assessment in the PCP's office. These three varied in their presentation format and the quality of cross-sectional validation studies, and none had longitudinal data for dementia prediction. Thus the existing test batteries show potential for use in primary care but further study is needed to demonstrate their feasibility and effectiveness in this setting. Show more

Keywords: Cognition, computers, mild cognitive impairment, neuropsychological tests, primary care

DOI: 10.3233/JAD-2010-091672

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 823-832, 2010

Authors: Waldstein, Shari R. | Wendell, Carrington Rice

Article Type: Review Article

Abstract: Cardiovascular (CV) diseases and their risk factors negatively impact the brain and neurocognitive function prior to stroke, dementia, or mild cognitive impairment (MCI). Indeed, a progression of neurocognitive and neurobiological impairments may be associated with increasingly severe manifestations of CV risk and disease. In samples ranging from children to elderly, a broad spectrum of CV risk factors, and both subclinical and clinical CV diseases, have been related to decrements in cognitive function and cognitive decline across multiple domains of performance including executive functions, attention, learning and memory, perceptuo-motor speed, and others. In contrast to the MCI literature, the possibility of …distinct subgroups has not been explored. Further, it remains unknown whether neurocognitive performance (or its pattern) per se can predict conversion to MCI and later dementia. We suggest that neurocognitive function may contribute to such prediction in concert with relevant radiological, genetic, biomedical, sociodemographic, and other data. To best do so, future research would benefit from inclusion of a breadth of neurocognitive tests that tap multiple domains of function and have historical sensitivity to vascular and neurodegenerative pathology, in addition to biological or radiological assessment of such pathology. Aggressive efforts at prevention and early intervention with CV risk may play a critical role in the prevention of MCI or dementia. Show more

Keywords: Brain, cardiovascular disease, cardiovascular risk factors, cognitive function, neuropsychology

DOI: 10.3233/JAD-2010-091591

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 833-842, 2010

Authors: Mosconi, Lisa | Berti, Valentina | Glodzik, Lidia | Pupi, Alberto | De Santi, Susan | de Leon, Mony J.

Article Type: Review Article

Abstract: The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring in the preclinical stage of the disease. Early diagnostics is necessary to identify and treat at risk individuals before irreversible neuronal loss occurs. In vivo imaging has long been used to evaluate brain structural and functional abnormalities as predictors of future AD in non-demented persons. Prior to development of amyloid-β (Aβ) tracers for positron emission tomography (PET), the most widely utilized PET tracer in AD was 2-[18F]fluoro-2-Deoxy-D-glucose (FDG) PET. For over 20 years, FDG-PET has been used to …measure cerebral metabolic rates of glucose (CMRglc), a proxy for neuronal activity, in AD. Many studies have shown that CMRglc reductions occur early in AD, correlate with disease progression, and predict histopathological diagnosis. This paper reviews reports of clinical and preclinical CMRglc reductions observed in association with genetic and non-genetic risk factors for AD. We then briefly review brain Aβ PET imaging studies in AD and discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Aβ-PET to improve the early detection of AD. Show more

Keywords: Amyloid-β, cerebral metabolic rate of glucose (CMRglc), normal aging, positron emission tomography, preclinical detection

DOI: 10.3233/JAD-2010-091504

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 843-854, 2010

Authors: Kitagawa, Kazuo

Article Type: Review Article

Abstract: Recent epidemiological studies have shown that hypertension is a significant risk factor for Alzheimer's disease (AD). Cerebral small vessel disease (CSVD) including silent cerebral infarction and white matter lesions could represent hypertensive target organ damage in the brain and may be reliable predictors for incident dementia. However, there have been few measures to classify those patients with CSVD who are at high risk for cognitive decline and dementia. Although cerebral hypoperfusion is central to the vascular hypothesis of AD, there have been no studies linking cerebral blood flow (CBF) and future cognitive decline. Using positron emission tomography, we have demonstrated …a moderate association between CBF under baseline conditions and cognitive decline during a 3-year follow-up study in 27 hypertensive patients (r=0.59, P=0.001). Findings from randomized clinical trials together with our results suggest that the preservation or improvement of CBF by anti-hypertensive treatment might be effective for the prevention of cognitive decline and dementia, especially in hypertensive patients with CSVD. Show more

Keywords: Cerebral blood flow, cerebral small vessel disease, cognitive decline, hypertension, positron emission tomography

DOI: 10.3233/JAD-2010-091324

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 855-859, 2010

Authors: de la Torre, Jack C.

Article Type: Review Article

Abstract: The dramatic rising incidence and costs of Alzheimer's disease (AD) require that research efforts and funding be primarily directed on either finding a cure or applying preventive measures to curb this disorder. A cure for AD appears unlikely when significant cognitive loss has occurred because the neuronal networks that controlled the perturbed cognitive abilities are either dead or irreversibly damaged and replacing them, even if it were technically possible, would not reconstruct the intellectual identity of the host. Prevention of risk factors to sporadic AD is a more realistic stratagem and treatment, when indicated, ideally should begin in cognitively intact …individuals as part of a mass screening effort. Prevention of modifiable risk factors to AD is cost-effective because it reduces hospice or hospital stay, repeated doctor visits, and long-term care. Presently, neurocognitive and neuroimaging tests are used with partial success in identifying persons at higher risk of AD but these tests can not pinpoint either a cause or a specific intervention that could attenuate disease progress. We previously proposed that carotid artery ultrasound +echocardiography together with ankle-brachail index (CAUSE+ABI) as mass screening tests in asymptomatic persons could detect not only cardio-cerebrovascular risk factors to AD, but also identify an indicated intervention. CAUSE+ABI are simple to perform, cost-effective, non-invasive, and reasonably accurate for the intended purpose. Additionally, detection of cardio-cerebrovasacular abnormalities long before expression of cognitive deterioration allows higher success rate with earlier treatment. Evidence-based medicine is recommended for optimizing clinical decision-making in evaluating AD risk factors and their treatment. Show more

Keywords: Alzheimer's disease, Alzheimer's risk factors, cognition, evidence-based medicine, neurodegeneration, prevention, ultrasound screen

DOI: 10.3233/JAD-2010-091579

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 861-870, 2010

Authors: Alsop, David C. | Dai, Weiying | Grossman, Murray | Detre, John A.

Article Type: Review Article

Abstract: Arterial spin labeling (ASL) enables the noninvasive, quantitative imaging of cerebral blood flow using standard magnetic resonance imaging (MRI) equipment. Because it requires no contrast injection, ASL can add resting functional information to MRI studies measuring atrophy and signs of ischemic injury. Key features of ASL technology that may affect studies in Alzheimer's disease are described. The existing literature describing ASL blood flow imaging applied to Alzheimer's disease and related dementia is reviewed, and the potential role of ASL in treatment and prevention studies of early Alzheimer's disease is discussed.

Keywords: Cerebral blood flow, diagnosis, imaging, magnetic resonance imaging, perfusion

DOI: 10.3233/JAD-2010-091699

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 871-880, 2010

Authors: van Rossum, Ineke A. | Vos, Stephanie | Handels, Ron | Visser, Pieter Jelle

Article Type: Review Article

Abstract: Disease modifying drugs for Alzheimer's disease (AD) are likely to be most effective when given in non-demented subjects. In this review we summarized biomarkers in cerebrospinal fluid (CSF) and blood that can predict AD-type dementia in subjects with mild cognitive impairment (MCI). In addition, we investigated whether these markers could reduce sample size and costs if used to select subjects for trials on the prevention of AD in subjects with MCI. A meta-analysis of markers that had been investigated in multiple studies showed that the combination of amyloid-β (Aβ1-42 and tau in CSF had the best predictive accuracy for …AD (odds ratio (OR) 18.1, 95% confidence interval (CI) 9.6–32.4). Aβ1-42 , total tau, and phosphorylated tau in CSF also predicted conversion, but with lower accuracy (OR 7.5 to 8.1). Plasma levels of Aβ1-40 , Aβ1-42 , the ratio Aβ1-42 /Aβ1-40 and homocysteine did not predict outcome. In a fictive trial design, the use of the combination of Aβ1-42 and tau in CSF in the selection of subjects could reduce sample size by 67% and trial costs by 60% compared to a trial in which unselected subjects with MCI would be enrolled. In conclusion, the combination of Aβ1-42 and tau in CSF is useful to select subjects for trials that aim to slow down the progression from MCI to AD-type dementia. Show more

Keywords: Alzheimer's disease, biomarkers, blood, cerebrospinal fluid, cost-benefit, decision analysis, mild cognitive impairment

DOI: 10.3233/JAD-2010-091606

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 881-891, 2010