Journal of Alzheimer's Disease - Volume 32, issue 3

Authors: Richard, Edo | Moll van Charante, Eric P. | van Gool, Willem A.

Article Type: Review Article

Abstract: Epidemiological studies have consistently shown that vascular risk factors including hypertension, diabetes, obesity, hypercholesterolemia, smoking, and lack of physical exercise are associated with an increased risk of cognitive decline and dementia. Neuroradiological and neuropathological studies have confirmed the importance of cerebrovascular lesions in the etiology of late onset dementia. We have reviewed the literature and conclude that up until now randomized controlled clinical trials targeting individual risk factors and assessing cognitive decline or dementia as an outcome have not convincingly shown that treatment of vascular risk factors can actually prevent or postpone cognitive decline and dementia. New studies targeting several …vascular risk factors at the same time and using cognitive decline or dementia as primary outcome might answer the question whether cognitive decline can really be postponed or even prevented. The design of such studies is not straightforward and long follow-up is required. In this review we discuss several pertinent methodological issues that need to be addressed to achieve an optimal design of new randomized controlled trials. Show more

Keywords: Cognitive decline, dementia, multi-component intervention, prevention, randomized controlled trials, vascular risk factors

DOI: 10.3233/JAD-2012-120772

Citation: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 733-740, 2012

Authors: Rojas, Julio C. | Bruchey, Aleksandra K. | Gonzalez-Lima, Francisco

Article Type: Research Article

Abstract: Cerebral hypometabolism characterizes mild cognitive impairment and Alzheimer's disease. Low-level light therapy (LLLT) enhances the metabolic capacity of neurons in culture through photostimulation of cytochrome oxidase, the mitochondrial enzyme that catalyzes oxygen consumption in cellular respiration. Growing evidence supports that neuronal metabolic enhancement by LLLT positively impacts neuronal function in vitro and in vivo. Based on its effects on energy metabolism, it is proposed that LLLT will also affect the cerebral cortex in vivo and modulate higher-order cognitive functions such as memory. In vivo effects of LLLT on brain and behavior are poorly characterized. We tested the hypothesis that in …vivo LLLT facilitates cortical oxygenation and metabolic energy capacity and thereby improves memory retention. Specifically, we tested this hypothesis in rats using fear extinction memory, a form of memory modulated by prefrontal cortex activation. Effects of LLLT on brain metabolism were determined through measurement of prefrontal cortex oxygen concentration with fluorescent quenching oximetry and by quantitative cytochrome oxidase histochemistry. Experiment 1 verified that LLLT increased the rate of oxygen consumption in the prefrontal cortex in vivo. Experiment 2 showed that LLLT-treated rats had an enhanced extinction memory as compared to controls. Experiment 3 showed that LLLT reduced fear renewal and prevented the reemergence of extinguished conditioned fear responses. Experiment 4 showed that LLLT induced hormetic dose-response effects on the metabolic capacity of the prefrontal cortex. These data suggest that LLLT can enhance cortical metabolic capacity and retention of extinction memories, and implicate LLLT as a novel intervention to improve memory. Show more

Keywords: Cytochrome oxidase, fear extinction, memory enhancement, mild cognitive impairment, mitochondrial respiration, neurotherapeutics, photobiomodulation

DOI: 10.3233/JAD-2012-120817

Citation: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 741-752, 2012

Authors: Feldstein, Carlos A.

Article Type: Review Article

Abstract: Epidemiological studies suggest an association between chronic blood pressure (BP) changes and Alzheimer's disease (AD). In particular, there is growing evidence that hypertensive people that do not have their BP adequately treated and controlled in midlife are more likely to develop AD in late-life. It has been hypothesized that cerebrovascular disease is a common pathway which connects hypertension and AD in individuals with apolipoprotein E genotype through brain hypoperfusion and hypoxia. This could accelerate amyloid-β aggregation that disrupts cell-to-cell connectivity and leads to eventual brain neuron loss. Also, high BP contributes to worsen AD by raising oxidative stress and inflammatory …response. Aging-related structural and functional disturbances appear to exacerbate the deleterious effect of chronic hypertension on cerebral blood flow autoregulation. There is evidence suggesting that some antihypertensive drug classes reduce the risk and progression of AD more than others. Further prospective randomized studies comparing different classes of antihypertensive drugs are needed to provide more evidence regarding their effects on AD risk. Hypotension could be a consequence of the incident dementia and conversely deteriorate the outcome of AD by worsening brain hypoperfusion. Frequent home BP monitoring should be carried out in AD patients to detect harmful orthostatic hypotension. Show more

Keywords: Alzheimer's disease, hypertension, hypotension, physiopathology

DOI: 10.3233/JAD-2012-120613

Citation: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 753-763, 2012

Authors: Richard, Florence | Pasquier, Florence

Article Type: Review Article

Abstract: Dementia is a widespread disorder with major medical, economic and societal costs. Controlling vascular conditions could be one way of delaying the progression of Alzheimer's disease (AD). In fact, vascular risk factors are implicated in AD occurrence. However, it has not been clearly determined whether these vascular factors also affect disease progression itself and thus whether controlling vascular conditions can slow this progression. The treatment of vascular risk factors could have an impact on disease progression by slowing the development of the vascular component. In the present article, we review the potential value of managing hypertension, diabetes, hypercholesterolemia or global …vascular risk factors in AD patients. Show more

Keywords: Alzheimer's disease, cerebrovascular disorders, control, disease progression, vascular risk factor

DOI: 10.3233/JAD-2012-121012

Citation: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 765-772, 2012

Authors: Ambrose, Charles T.

Article Type: Research Article

Abstract: Angiogenesis directs development of the brain's microcirculation during antenatal and postnatal development, but its role later in life is less well recognized. I contend that during senescence a reduced cerebral capillary density accounts in part for the vascular cognitive impairment observed in many older persons and possibly for some forms of Alzheimer's disease. I propose that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age. To support this hypothesis I have examined the neurological literature for relevant studies on cerebral capillary density …and neuroangiogenesis throughout the three stages of life and in persons with senile dementias. Finally, I discuss therapeutic approaches employing angiogenic factors for treating vascular cognitive impairment and Alzheimer's disease. Show more

Keywords: Alzheimer's disease, angiogenesis, capillary density, senile dementias, vascular cognitive impairment

DOI: 10.3233/JAD-2012-120067

Citation: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 773-788, 2012

Article Type: Other

DOI: 10.3233/JAD-2012-120677B

Citation: Journal of Alzheimer's Disease, vol. 32, no. 3, pp. 789-791, 2012