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

Authors: de la Torre, Jack C.

Article Type: Editorial

DOI: 10.3233/JAD-141800

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S327-S328, 2014

Authors: Stephan, Blossom C.M. | Brayne, Carol

Article Type: Review Article

Abstract: Accurate detection of individuals with cognitive impairment and dementia in addition to identification of those at high risk of future disease is important to guide clinical care, and has research implications regarding clinical trial recruitment and development of dementia preventative strategies. In this narrative review, we describe new proposed criteria for early diagnosis of Alzheimer's disease (AD). We also explore risk factors for dementia and evaluate methods for screening for increased risk of incident disease. We highlight variability in different diagnostic approaches. Additional work needs to be done to validate new methods across different settings (such as population-based, primary care, …and memory clinics), age, and ethnic groups. Having an accurate method to assess for dementia and predict risk in routine clinical care will aid decision making and could ultimately lead to disease prevention. Show more

Keywords: Alzheimer's disease, cognition, dementia, early diagnosis, screening

DOI: 10.3233/JAD-141413

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S329-S338, 2014

Authors: Cheung, Carol Yim-lui | Ong, Yi-Ting | Ikram, M. Kamran | Chen, Christopher | Wong, Tien Yin

Article Type: Review Article

Abstract: Although cerebral small vessel disease has been implicated in the development of Alzheimer's disease (AD), the cerebral microcirculation is difficult to visualize directly in vivo. As the retina and the brain share similar embryological origin, anatomical features and physiological properties with the cerebral small vessels, the retinal vessels thus offer a unique and easily accessible “window” to study the correlates and consequences of cerebral small vessel diseases in vivo. Retinal microvasculature can now be visualized, quantified and monitored non-invasively using state-of-the-art retinal imaging technology. Recent clinic- and population-based studies have demonstrated a link between retinal vascular changes and dementia, in …particular AD, and cerebral small vessel disease. In this review, we summarize the current findings on retinal vascular changes such as retinopathy signs and changes in novel retinal vascular network parameters and retinal vascular caliber with dementia, cognitive dysfunction and cerebral small vessel disease, and discuss possible future research to further evaluate whether retinal vascular imaging might help to elucidate vascular mechanisms contributing to the development of AD and provide additional value in predicting who may be at risk of developing AD. Show more

Keywords: Alzheimer's disease, microcirculation, retina, retinal vascular changes, retinal vasculature, small vessel disease

DOI: 10.3233/JAD-141596

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S339-S352, 2014

Authors: Dufouil, Carole | Seshadri, Sudha | Chêne, Geneviève

Article Type: Research Article

Abstract: There is growing evidence for the importance of cardiovascular risk factors in dementia development, including Alzheimer's disease. As cardiovascular risk profiles vary greatly by gender, with men suffering a greater burden of cardiovascular risk in midlife, this could lead to differences in dementia risk. To explore current evidence on the association between components of the cardiovascular risk profile and dementia risk in women and men, we reviewed all studies reporting the risk of dementia associated with cardiovascular risk factors stratified by gender and found 53 eligible articles out of over 4,000 published since the year 2000. Consistent results were found: …1) for exposures acting specifically in women: Overweight/obesity (harmful) and physical activity (protective), and 2) for exposures acting similarly in women and men: Moderate alcohol (protective) and hypertension, diabetes, and depression (harmful). A modified effect of tobacco or high cholesterol/statin use remained controversial. Available data do not allow us to assess whether selection of men with healthier cardiovascular profile (due to cardiovascular death in midlife) could lead in late life either to a difference in the distribution of risk factors or to a differential effect of these risk factors by gender. We recommend that results on dementia risk factors, especially cardiovascular ones, be reported systematically by gender in all future studies. More generally, as cardiovascular risk profiles evolve over time, more attention needs to be paid to the detection and correction of cardiovascular risk factors, as early as possible in the life course, and as actively in women as in men. Show more

Keywords: Alzheimer's disease, cardiovascular diseases, dementia, prevention, risk factors, women

DOI: 10.3233/JAD-141629

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S353-S363, 2014

Authors: Tomek, Aleš | Urbanová, Barbora | Hort, Jakub

Article Type: Review Article

Abstract: Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by an increasing incidence. One of the pathologic processes that underlie this disorder is impairment of brain microvasculature. Transcranial ultrasound is a non-invasive examination of cerebral blood flow that can be employed as a simple and useful screening tool for assessing the vascular status of brain circulation in preclinical and clinical stages of AD. The objective of this review is to explore the utility of using a transcranial ultrasound to diagnose AD. With transcranial ultrasound, the most frequently studied parameters are cerebral blood flow velocities and pulsatility indices, cerebrovascular reserve capacity, …and cerebral microembolization. On the basis of current knowledge, we recommend using as a transcranial Doppler sonography screening method of choice the assessment of cerebrovascular reserve capacity with breath-holding test. Show more

Keywords: Alzheimer's disease, breath-holding test, cerebrovascular reserve capacity, transcranial doppler sonography, transcranial color coded duplex ultrasonography, minimal cognitive impairment

DOI: 10.3233/JAD-141803

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S365-S374, 2014

Authors: Belleville, Sylvie | Fouquet, Céline | Duchesne, Simon | Collins, D. Louis | Hudon, Carol | the CIMA-Q group: Consortium for the Early Identification of Alzheimer's disease-Quebec

Article Type: Research Article

Abstract: In this paper, we review studies that have investigated whether neuropsychological, neuropsychiatric, and neuroimaging measures predict decline to Alzheimer's disease (AD). Prospective neuropsychological studies indicate that cognitive performance may be an excellent indicator of future progression from mild cognitive impairment (MCI) to AD, particularly when episodic memory is combined with tasks relying on executive control and language tasks. Research on neuropsychiatric symptoms reveal that depression, apathy, anxiety, and sleep disturbances can contribute to predictive models, though their sensitivity is typically lower than that found with cognitive measures. Finally, different structural brain imaging markers reveal excellent predictive accuracy. The paper discusses …issues that will have to be addressed in future studies. First, it will be necessary to increase the evaluation of combined markers, as this may considerably improve predictive accuracy. Second, it will be necessary to move to earlier stages than MCI in order to expand the detection window. Third, processes of compensation and plasticity will have to be better investigated as research moves into earlier stages. The Consortium for the early identification of AD-Quebec (CIMA-Q) is presented as an instance of this approach, and potential batteries of measures are proposed. Show more

Keywords: Alzheimer's disease, cognition, early detection of disease, longitudinal studies, mild cognitive impairment, neuroimaging, neuropsychiatry

DOI: 10.3233/JAD-141470

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S375-S382, 2014

Authors: Mataró, Maria | Soriano-Raya, Juan José | López-Olóriz, Jorge | Miralbell, Júlia | Dacosta-Aguayo, Rosalia

Article Type: Review Article

Abstract: Cerebrovascular disease (CVD) is a major cause of age-related cognitive decline and dementia. The identification of cognitive-related cerebrovascular markers is crucial in the early detection of individuals at high risk of cognitive decline. In vivo markers of CVD can help to characterize the underlying pathology, stage the progression of the disease, as well as identify and monitor candidates who could benefit from preventive interventions. We review the most common cerebrovascular markers of cognitive decline in subclinical individuals. These include neuroimaging, sonographic, and blood markers.

Keywords: Biomarkers, blood markers, cerebrovascular disease, cognitive impairment, MRI markers, sonographic markers

DOI: 10.3233/JAD-141443

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S383-S391, 2014

Authors: Mortamais, Marion | Artero, Sylvaine | Ritchie, Karen

Article Type: Review Article

Abstract: There is growing evidence that vascular health plays a significant role in the etiology of clinical Alzheimer's disease (AD). Understanding the timing of vascular changes in relation to progression from cognitive impairment to AD has become of increasing importance, being both possible pre-clinical markers and potentially modifiable risk factors. White matter hyperintensities (WMH) detected in vivo with magnetic resonance imaging, are commonly used to assess cerebrovascular burden in cognitive impairment and appear to be associated with an increased risk of cognitive decline due to many causes. The present review examines specifically the association between WMH and AD and its related …biomarkers. Overall, current findings across the literature suggest that WMH may predict AD at least a decade before the clinical stage of the disease, independently of biomarkers of AD pathology, thus indicating that vascular factors may constitute important targets for pre-clinical detection and intervention. Show more

Keywords: Alzheimer's disease, biomarker, cerebrovascular disease, magnetic resonance imaging, white matter hyperintensities

DOI: 10.3233/JAD-141473

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S393-S400, 2014

Authors: Scuteri, Angelo | Wang, HongYu

Article Type: Review Article

Abstract: Carotid-femoral pulse wave velocity (PWV), an index of large artery stiffness, is a good proxy of arterial aging and also an independent marker of cardiovascular disease. A consistently growing number of studies has shown a significant inverse association of arterial aging and cognitive function: the greater the PWV, the lower the cognitive performance (and the greater its decline over time)-regardless of heterogeneity in study populations, sample size, and measure of cognitive functions adopted in each study. Therefore the epidemiological evidence and the biological plausibility require adoption of strategies to foster the routine measurement of PWV and cognitive function measurements in …each and every older subject, particularly those at higher cardiovascular risk. Consistently, limited available healthcare resources should be progressively shifted from a sterile differential diagnosis between Alzheimer-type and vascular dementia to interventions aimed to reduce PWV and, thus, to prevent dementia before its onset or to decrease its rate of progression. Show more

Keywords: Arterial aging, arterial stiffness, cognition, dementia, marker, prevention, pulse wave velocity

DOI: 10.3233/JAD-141416

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S401-S410, 2014

Authors: Wierenga, Christina E. | Hays, Chelsea C. | Zlatar, Zvinka Z.

Article Type: Review Article

Abstract: There is growing recognition that cerebral hypoperfusion is related to the pathogenesis of Alzheimer's disease (AD), implicating the measurement of cerebral blood flow (CBF) as a possible biomarker of AD. The ability to identify the earliest and most reliable markers of incipient cognitive decline and clinical symptoms is critical to develop effective preventive strategies and interventions for AD. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) measures CBF by magnetically labeling arterial water and using it as an endogenous tracer. Studies using ASL MRI in humans indicate that CBF changes are present several years before the development of the clinical …symptoms of AD. Moreover, ASL-measured CBF has been shown to distinguish between cognitively normal individuals, adults at risk for AD, and persons diagnosed with AD. Some studies indicate that CBF may even be sensitive for predicting cognitive decline and conversion to mild cognitive impairment and AD over time. Taken together, evidence suggests that the current staging models of AD biomarker pathology should incorporate early changes in CBF as a useful biomarker, possibly present even earlier than amyloid-β accumulation. Though still a research tool, ASL imaging is a promising non-invasive and reliable method with the potential to serve as a future clinical tool for the measurement of CBF in preclinical AD. Show more

Keywords: Alzheimer's disease, arterial spin labeling, cerebral blood flow, cerebrovascular disorders, cognition, mild cognitive impairment, neuroimaging, neurovascular dysfunction, perfusion

DOI: 10.3233/JAD-141467

Citation: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S411-S419, 2014