Archives for March 2013

Update on Hypertension and Alzheimer’s Disease

Neurol Res. 2006 Sep;28(6):605-11.

Update on hypertension and Alzheimer’s disease

Skoog IGustafson D.


Institute of Neuroscience and Physiology, Section of Psychiatry, Unite of Neuropsychiatric Epidemiology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.


Several studies report that blood pressure is increased in victims of Alzheimer’s disease (AD) decades before the onset of the disease. Years before onset of Alzheimer’s disease, blood pressure start to decrease and continues to decrease during the disease process. High blood pressure has also been related to pathological manifestations of Alzheimer’s disease (senile plaques, neurofibrillary tangles, hippocampal atrophy). The exact mechanism behind these associations is not clear.

Hypertension is also a risk factor for stroke, ischemic white matter lesions, silent infarcts, general atherosclerosis, myocardial infarction and cardiovascular diseases, and often clusters with other vascular risk factors, including diabetes mellitus, obesity and hypercholesterolemia. Also these risk factors have been related to Alzheimer’s disease.

Hypertension may thus cause cerebrovascular disease that may increase the possibility for individuals with AD encephalopathy to express a dementia syndrome. Hypertension may also lead to vessel wall changes in the brain, leading to hypoperfusion, ischemia and hypoxia which may initiate the pathological process of AD. Finally, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated.

Several observational studies have reported that use of antihypertensives decreases risk of AD. Even though hypertension only results in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total number of demented individuals.


National Center for Biotechnology Information


Diet and Alzheimer’s Disease Risk Factors or Prevention

Expert Rev Neurother. 2011 May;11(5):677-708. doi: 10.1586/ern.11.56.

Diet and Alzheimer’s disease risk factors or prevention: the current evidence

Solfrizzi VPanza FFrisardi VSeripa DLogroscino GImbimbo BPPilotto A.


Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Bari, Italy.


Preventing or postponing the onset of Alzheimer’s disease (AD) and delaying or slowing its progression would lead to a consequent improvement of health status and quality of life in older age. Elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI).

Furthermore, at present, epidemiological evidence suggests a possible association between fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA; in particular, n-3 PUFA) and a reduced risk of cognitive decline and dementia. Poorer cognitive function and an increased risk of vascular dementia (VaD) were found to be associated with a lower consumption of milk or dairy products. However, the consumption of whole-fat dairy products may be associated with cognitive decline in the elderly.

Light-to-moderate alcohol use may be associated with a reduced risk of incident dementia and AD, while for VaD, cognitive decline and predementia syndromes, the current evidence is only suggestive of a protective effect. The limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supports a protective role of these macronutrients against cognitive decline, dementia and AD.

Only recently, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micro- and macro-nutrients already separately proposed as potential protective factors against dementia and predementia syndromes.

In fact, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD and a decreased all-cause mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk of AD, but also of predementia syndromes and their progression to overt dementia.

Based on the current evidence concerning these factors, no definitive dietary recommendations are possible. However, following dietary advice for lowering the risk of cardiovascular and metabolic disorders, high levels of consumption of fats from fish, vegetable oils, nonstarchy vegetables, low glycemic index fruits and a diet low in foods with added sugars and with moderate wine intake should be encouraged. Hopefully this will open new opportunities for the prevention and management of dementia and AD.


National Center for Biotechnology Information


Brain Plasticity and Alzheimer’s Disease

(Society for Neuroscience) The discovery that the human brain can produce new cells in adulthood offers just one example of how adaptable the brain is throughout life. With this knowledge, researchers are investigating how normal aging as well as neurodegenerative diseases like Alzheimer’s disease affect that adaptability, and how we can maintain healthy brain function as our brains age. Future research may one day allow scientists to capture the adult brain’s enormous capacity to adapt in order to help prevent or perhaps even reverse memory-robbing Alzheimer’s disease.

The Discovery: The Brain is Adaptable Throughout Life

When scientists discovered that the brain could create new brain cells in adulthood, they introduced a new way of thinking that could one day help treat or delay onset of Alzheimer’s disease (AD). AD is the most common form of cognitive dementia, the loss of higher mental functions like memory.

The image shows the addition of new neurons in the adult  mouse hippocampus — the brain region involved in learning and memory. This birth of  new cells is a major finding in showing how adaptable the brain is, even in adulthood. (Brain cells labeled blue-green are eight weeks old, while cells labeled red are at most four  weeks old.) Credit: Reprinted with permission from Gage, F. and Zhao, C. Laboratory of  Genetics LOG-G; The Salk Institute for Biological Studies. 2007.

New Discovery, New Belief

Researchers in the 1960s were curious to understand more about growth and repair in the adult brain, and conducted a number of experiments with rodents to help illuminate these processes. They made an amazing and unexpected discovery: newly created cells that later transformed into what appeared to be neurons, or brain cells.

The discovery was not initially recognized for the breakthrough it was because most experts thought that the brain finished developing and changing early in life and did not produce more neurons. Additionally, scientists faced the challenge of proving that the newly created cells were neurons.

Further advances came from explorations of learning conducted by researchers lured by birdsong. Years after the initial discoveries, advanced brain imaging techniques helped establish the existence, in adult canaries, of these precursor cells, or stem cells, that reproduced, migrated to other brain areas, and matured into neurons. This process, called neurogenesis, is just one example of how plastic or adaptable the brain is.

Human Discoveries

Further research has proved that the brains of adult humans also undergo neurogenesis, revealing the plasticity of the brain throughout our lives. Scientists located adult human neurogenesis sites in the dentate gyrus of the hippocampus — the brain region involved in learning and memory — and the subventricular zone in the region where fluid that helps protect the brain and spinal cord is made.

Indeed, scientists worldwide, working in many different specialties, have found that the human brain is highly plastic, possessing the ability not only to create new neurons, but to modify networks of neurons to better cope with new circumstances.

These collective discoveries may pave the way for further understanding of how old age and conditions like AD affect plasticity, and may help researchers find ways to preserve it.

New Application: Enhancing the Brain’s Plasticity

Once scientists realized the adult brain’s enormous capacity for plasticity, they could study the effects of aging and Alzheimer’s disease on that capability and explore ways to maintain healthy brain function.

Left: These three-dimensional projections of brain positron emission tomography scans (outer brain surface) show amyloid plaques and tau tangles labeled by a chemical marker — the first developed to tag physical evidence of Alzheimer’s disease (AD) in living people. The control image is from an older person without AD. Warmer colors (red, yellow)indicate higher levels of plaques and tangles. Credit: Reprinted from Lancet Neurology, 7, G. Small et al., Current and future uses of neuroimaging for cognitively impaired patients, 161–72, © (2008), with permission from Elsevier.

Right: This figure shows the effects of exercise on levels of brain-derived neurotrophic factor (BDNF) in the hippocampus of rats. Growth factors like BDNF help many neurons survive. Levels of the message that makes BDNF are much higher in exercising rats(A) than in sedentary animals (B). Red and yellow denote the highest level of BDNF, while green and blue denote the lowest. Credit: Alzheimer’s Disease Education and Referral Center, a service of the National Institute on Aging.

Declining Plasticity in Old Age and in People with Alzheimer’s Disease

Brain deterioration begins well before old age. Scientists believe that changes in plasticity at brain synapses — the junctions where neurons signal to each other — and the loss of neurons may be responsible for this decline in function.

Interestingly, these changes also precede AD impairments and many harmful precursors of AD, like amyloid beta deposits, tau tangles, ApoE4 proteins, and brain inflammation. These AD hallmarks damage areas of the brain responsible for learning, memory, and cognition by further impairing synapses and contributing to cell death. With AD patients, early neuron loss and changes in synapse function have been observed in the hippocampus and neocortex — the very brain regions involved in language, memory, and other higher cognitive functions.

An Enriched Environment Plays a Role

Researchers have found at least one clear link between brain plasticity and healthy aging: They know that a rich, stimulating environment can enhance and maintain brain plasticity, even in old age and with AD patients. Studies of aged rodents modeled with and without AD show that regular social interaction, exercise, and a healthful diet, as well as cardiovascular exercise, can increase neurogenesis, neuron communication, and hippocampus-related learning, and can decrease levels of amyloid beta deposits. In addition, exercise has been shown to help increase production of proteins and blood vessels that support the growth and survival of cells.

In humans, research has revealed that exercise enhances cognitive function and protects against dementia and neurodegenerative diseases like AD — just one line of discovery that shows promise against these debilitating conditions.

Health Implications: Promise for Treating Alzheimer’s Disease

With new knowledge of how normal aging and conditions like Alzheimer’s disease affect plasticity and how environment can enhance brain function, scientists can investigate the power of plasticity in treating AD.

As Alzheimer’s disease progresses, it kills brain cells mainly in the hippocampus and  cortex, which leads to impairments in learning, memory, and thinking. Harnessing the brain’s capacity to adapt in adulthood may one day help prevent and treat Alzheimer’s disease. Credit: Adapted and reprinted with permission from the Alzheimer’s Association. © 2008 Alzheimer’s Association. All rights reserved.

Maintaining Healthy Brain Function

Targeting areas in the brain that may be more vulnerable to aging and AD, such as the hippocampus, may enhance overall brain function and help slow or stop the natural decline in brain plasticity.

Using strategies to maintain healthy brain function in youth and increasingly in old age may also help delay or prevent decreasing brain plasticity. Cardiovascular exercise and other behavioral changes — such as switching to a more healthful diet — may stave off cognitive decline, keep brain networks flexible, increase neurogenesis, and enhance processes that aid in the growth and survival of both existing and new cells.  

Boosting Brain Plasticity as Treatment

For now, encouraging efforts to enhance brain plasticity at the first sign of neuron dysfunction, before AD impairments develop, may be the best bet in treating or delaying onset of the disease.

For example, brain plasticity exercises may one day help AD patients. These include demanding sensory, cognitive, and motor activities that reengage and strengthen the brain systems involved in learning. Such brain plasticity training has helped normal aging adults improve memory.

Many drug trials also are underway that target the early development of amyloid beta, tau, ApoE4, and brain inflammation to prevent or reverse their negative effects on brain plasticity and cell loss, and ultimately on learning and memory.

Researchers have much more to learn about preserving and enhancing plasticity as a way to defend against memory-robbing conditions that strike in old age. The discovery of adult neurogenesis is spurring significant progress, but only continued research will help scientists harness the adult brain’s enormous capacity for plasticity to prevent or delay the onset of AD, and to treat the more than 4.5 million Americans diagnosed with it.


Copyright © 2011  Society for Neuroscience


Computer Activities, Physical Exercise, Aging, and Mild Cognitive Impairment

Mayo Clin Proc. 2012 May;87(5):437-42. doi: 10.1016/j.mayocp.2011.12.020.

Computer activities, physical exercise, aging, and mild cognitive impairment: a population-based study.

Geda YESilber TCRoberts ROKnopman DSChristianson TJPankratz VSBoeve BFTangalos EGPetersen RC.

Department of Psychiatry and Psychology, Mayo Clinic, Scottsdale, AZ 85259, USA.


To examine the association between computer use, physical exercise, aging, and mild cognitive impairment (MCI).

Patients and Methods

The Mayo Clinic Study of Aging is a population-based study of aging and MCI in Olmsted County, Minnesota. The study sample consists of a random sample of 926 nondemented individuals aged 70 to 93 years who completed self-reported questionnaires on physical exercise, computer use, and caloric intake within 1 year of the date of interview. The study was conducted from April 1, 2006, through November 30, 2008. An expert consensus panel classified each study participant as cognitively normal or having MCI on the basis of published criteria.


Using a multivariable logistic regression model, we examined the impact of the presence during the study period of 2 lifestyle factors (physical exercise and computer use) after adjusting for a third lifestyle factor (caloric intake) on aging and MCI. We also adjusted for age, sex, education, medical comorbidity, and depression. The median daily caloric intake was significantly higher in participants with MCI than in controls (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P=.001). Participants who engaged in both moderate physical exercise and computer use had significantly decreased odds of having MCI (odds ratio [95% confidence interval], 0.36 [0.20-0.68]) compared with the reference group. In the interaction analyses, there was an additive interaction (P=.012) but not multiplicative interaction (P=.780).


In this population-based sample, the presence of both physical exercise and computer use as assessed via survey was associated with decreased odds of having MCI, after adjustment for caloric intake and traditional confounders.


National Center for Biotechnology Information


Efficacy of Donepezil, Rivastigmine, Galantamine, and Memantine in Relation to Severity of Alzheimer’s Disease

J Alzheimers Dis. 2013 Feb 14. [Epub ahead of print]

A Meta-Analysis of the Efficacy of Donepezil, Rivastigmine, Galantamine, and Memantine in Relation to Severity of Alzheimer’s Disease.

Di Santo SG, Prinelli F, Adorni F, Caltagirone C, Musicco M.


Fondazione IRCCS “Santa Lucia”, Roma, Italy.



Randomized clinical trials have evaluated the efficacy of acetylcholinesterase inhibitors (AChE-Is) and memantine across a wide range of Alzheimer’s disease (AD) severity. However, these drugs are prescribed and reimbursed according to precise upper and lower cut off scores of cognitive tests.


To verify whether the efficacy of pharmacological treatment had any dependence on the severity of dementia in AD patients.


Published English-language randomized, placebo-controlled trials evaluating the efficacy of AChE-Is or memantine at any dose, over any length of time, in patients with any severity of dementia due to AD were included.

Cognitive, behavioral, and functional outcomes were extracted from each study and multiple outcomes from the same trial were pooled to obtain a unique indicator of efficacy for cognition, functional impairment, and behavioral and psychological disturbances.

The existence of a relationship between size of the treatment effect and severity of dementia, measured with the Mini-Mental State Examination, was determined using parametric and non-parametric correlation analyses.


Both AChE-Is and memantine had significant effects on cognition. Functional and psycho-behavioral outcomes were reported less frequently but also showed significant efficacy of treatment. High heterogeneity among studies was found within and between the different drugs. The efficacy of all drugs except memantine was independent from dementia severity in all domains. Memantine effect on functional impairment was better in more severe patients.


The modest beneficial effects of anti-dementia drugs on cognition are independent from dementia severity. Memantine is more effective on functional incompetence only in severe patients.


PMID: 23411693 PubMed – as supplied by publisher

National Center for Biotechnology Information


Effects of Music Therapy on Behavioral and Psychological Symptoms of Dementia

Ageing Res Rev. 2013 Mar 16. pii: S1568-1637(13)00013-5. doi: 10.1016/j.arr.2013.02.003. [Epub ahead of print]

Effects of music therapy on behavioral and psychological symptoms of dementia: A systematic review and meta-analysis.

Ueda T, Suzukamo Y, Sato M, Izumi SI.


Department of Physical Medicine and Rehabilitation, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address:


Behavioral and psychological symptoms of dementia (BPSD) are common problems for patients and caregivers. Although music therapy is considered a non-pharmacological intervention for the management of BPSD, its effectiveness remains unclear. This study aimed to investigate the effects of music therapy on BPSD, cognitive function, and activities of daily living in patients with dementia.

A literature search was conducted in the following databases: MEDLINE, CINAHL, PsycINFO, and Igaku Chuo Zasshi. We selected 20 studies, including randomized controlled trials, controlled clinical trials, cohort studies, and controlled trials, and conducted a meta-analysis using standardized mean differences (SMD). The results showed that music therapy had moderate effects on anxiety [SMD, -0.64; 95% confidence interval (CI), -1.05 – -0.24; p=0.002] and small effects on behavioral symptoms (SMD, -0.49; 95% CI, -0.82 – -0.17; p=0.003). In studies of duration >3 months, music therapy had large effects on anxiety (SMD, -0.93; 95% CI, -1.72 – -0.13; p=0.02).

The present systematic review and meta-analysis suggests that music therapy is effective for the management of BPSD.


National Center for Biotechnology Information


Keeping a Dementia Journal

(Alzheimer’s Society) When Chris Young’s father-in-law George was diagnosed with dementia, he kept a journal of his and his wife’s experiences in caring for him. Luke Bishop reports on Chris’ account of how useful this turned out to be

The day after George was told he had Alzheimer’s disease in June 2003, Chris Young started to write a journal to help him confront and cope with the impact of the diagnosis.

Chris, who married George’s daughter Glynis just three weeks after the diagnosis, had kept a personal diary from time to time over the years to record events, experiences and his reactions to them so keeping a journal about George seemed like a natural thing to do.

When George passed away seven years later, Chris had some 130 pages of notes which he titled The clock, the table and the umbrella: a journey with George.

Considered Decisions

Over those years the diary would prove a benefit to Chris and Glynis in making informed and considered decisions about George’s carefinances, legal status and even social life.

Chris explains,

‘As events unfolded, we were inevitably immersed in the totality of decision-making that is a constant part of caring for someone with Alzheimer’s and these were reflected in the journal.

‘From putting in place an enduring power of attorney in order to manage George’s financial affairs on his behalf, to organising as much of a social life as possible to encourage interaction and stimulation.’

This was also the case with finding a suitable care home – and finally a nursing home – which would provide him with a good quality of care, as well as working with the care home manager to keep his care plan up to date.

‘The main thing for us was spending as much time as possible with George to give him constant reassurance that he was still a well-loved member of the family and would never be neglected or abandoned.’

Recurring Subjects

Shortly before his diagnosis George moved from his home in Hemel Hempstead to live closer to Chris and Glynis in Cowes on the Isle of Wight. They made sure to involve George in their lives as much as possible.

The journal was not only a means of recording practical information but Chris would record scraps of conversation with George which, as his abilities to communicate declined, proved useful in helping to interpret what he was trying to say.

‘The journal – in which I tried to capture some of these fragmented conversations – allowed us to keep track of subjects that kept recurring so we could feed them back to him when things got confusing.’

Treasured Memories

More than anything for Chris, the diary was a means of recording treasured though sometimes distressing memories about George, a gregarious man whom he loved not only as a father-in-law, but also as a friend who was lost to Alzheimer’s. Chris made sure to note down the positive experiences he and Glynis had with George and those moments of humour that can punctuate the challenges of caring for someone with dementia.

‘The more you know the person before the fog of the disease descends, the more I believe you can detect the true personality in spite of the fog – and the more you can take hold of their hand and look them in the eye and still see a glimmer of light in spite of all the gloom.

‘Keeping a journal was my way of ensuring that I never lost the crystal clear, vital sense of George’s humanity – his dignity and fulfilment as a complete human being – as a loving husband, father, grandfather, great-grandfather, friend.’

Revisiting Good Things

Although Chris stopped adding to the journal following George’s death in September 2010, he has circulated it among some of his friends. He believes journal-making can provide a practical record as well as an emotionally satisfying outlet and a helpful resource for others who have a loved one with dementia.

Chris says,

‘In years to come I think Glynis and I will go back through the diary to revisit the good things that happened at the time and reassure ourselves that we did everything we could under the circumstances.’

Alzheimer’s Society has a dedicated section of its website where anyone affected by dementia can share stories and poems about their experiences with others. If you would like to contribute your story, visit


All content © 2013 Alzheimer’s Society.


Antioxidants Do Not Protect Against Dementia or Stroke Risk

Neurology. 2013 Mar 5;80(10):904-10. doi: 10.1212/WNL.0b013e3182840c84. Epub 2013 Feb 20.

Total antioxidant capacity of the diet and major neurologic outcomes in older adults.

Devore EE1, Feskens E, Ikram MA, den Heijer T, Vernooij M, van der Lijn F, Hofman A, Niessen WJ, Breteler MM.



To evaluate total antioxidant capacity of the diet, measured by the ferric-reducing antioxidant power (FRAP) assay, in relation to risks of dementia and stroke, as well as key structural brain volumes, in the elderly.


We prospectively studied 5,395 participants in the Rotterdam Study, aged 55 years and older, who were dementia free and provided dietary information at study baseline; 5,285 individuals were also stroke free at baseline, and 462 were dementia and stroke free at the time of an MRI brain scan 5 years after baseline. Dietary data were ascertained using a semiquantitative food-frequency questionnaire, and combined with food-specific FRAP measurements from published tables; this information was aggregated across the diet to obtain “dietary FRAP scores.” Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of dementia and stroke, and multivariable-adjusted linear regression was used to estimate mean differences in structural brain volumes, across tertiles of dietary FRAP scores.


During a median 13.8 years of follow-up, we identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, we observed no associations between dietary FRAP scores and risk of dementia (p trend = 0.3; relative risk = 1.12, 95% confidence interval = 0.91-1.38, comparing the highest vs lowest FRAP tertiles) or risk of stroke (p trend = 0.3; relative risk = 0.91, 95% confidence interval = 0.75-1.11, comparing extreme FRAP tertiles); results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes as well.