Tag Archives: Alzheimer’s

Analysis of health insurance data suggests preventive effect

Type 2 diabetes most commonly occurs in late adulthood, and it has long been known that it can affect the patient’s mental health: Patients have a greater risk of developing dementia than non-diabetics. However, how does antidiabetic medication influence this risk? Researchers have investigated this issue in a new study based on data from the years 2004 to 2010 provided by the German public health insurance company AOK. These data set comprises information about diseases and medication related to more than 145,000 men and women aged 60 and over.

The analysis confirmed previous findings that diabetics have an increased risk of developing dementia. However, it was also found that this risk can significantly be modified by pioglitazone. This drug is taken as tablets. It is applied in short-term as well as in long-term treatment of diabetes as long as the body is still capable of producing its own insulin.

“Treatment with pioglitazone showed a remarkable side benefit. It was able to significantly decrease the risk of dementia,” says co-author Gabriele Doblhammer. “The longer the treatment, the lower the risk.” Risk reduction was most noticeable when the drug was administered for at least two years. Diabetics given this treatment developed dementia less often than non-diabetics. “The risk of developing dementia was around 47 percent lower than in non-diabetics, i.e. only about half as large.”, she said.

Protection against nerve cell damage

Pioglitazone improves the effect of the body’s own insulin. Moreover, laboratory tests have long indicated that it also protects the nerve cells. The current results are therefore no surprise to neuroscientist Michael Heneka. “Pioglitazone is an anti-inflammatory drug that also inhibits the deposition of harmful proteins in the brain,” he says.

However, Heneka emphasizes that the exact mechanisms are not yet understood: “Our study suggests that pioglitazone has a preventive effect. This happens when the drug is taken before symptoms of dementia manifest. Thus, it protects in particular against Alzheimer’s, the most common form of dementia. The causes for this, whether pioglitazone only has this protective effect in diabetics or if it would also work in non-diabetics – all these questions have yet to be answered. The next logical step would therefore be clinical studies. These studies would specifically investigate the effect of pioglitazone and other antidiabetics on dementia.

Source: Eurekalert

Two studies in the May 19 issue of JAMA analyze the prevalence of the plaque amyloid among adults of varying ages, with and without dementia, and its association with cognitive impairment.

The earliest recognizable pathological event in Alzheimer’s Disease (AD) is cerebral amyloid-beta aggregation (protein fragments that clump together to form plaque).This pathology may be present up to 20 years before the onset of dementia.

Therefore, estimates of the prevalence of amyloid pathology in persons without dementia are needed to better understand the development of AD and to facilitate the design of AD prevention studies. Initiation of treatment for AD in the pre-dementia phase, when neuronal damage is still limited, may be crucial to have clinical benefit.

Led by Pieter Jelle Visser at VU University Medical Center in Amsterdam and Maastricht University, The Netherlands, these two studies compiled amyloid PET and cerebrospinal fluid (CSF) biomarker data from thousands of participants, and represent the largest data sets to date on how commonly amyloid builds up in people’s brains.

One meta-analysis looked at the prevalence of amyloid in cognitively normal people, and concluded that amyloid creeps into the brain 20 to 30 years before dementia can be diagnosed. This was particularly true for people who carry an ApoE4 allele; indeed, they developed amyloid at a younger age.

In the second study, the researchers compared amyloid prevalence among people clinically diagnosed with AD or other dementias, including dementia with Lewy bodies, frontotemporal dementia, and corticobasal syndrome. They found that the prevalence of brain amyloid in people diagnosed with most non-AD dementias was higher with increasing age. They concluded that older people may be likelier to have multiple pathologies, or to have been misdiagnosed. The data may help researchers set inclusion criteria for clinical trials, or make better diagnoses.

“The observation that key risk factors for AD-type dementia are also risk factors for amyloid positivity in cognitively normal persons provides further evidence for the hypothesis that amyloid positivity in these individuals reflects early AD,” the researchers wrote. “Our study also indicates that development of AD pathology can start as early as age 30 years, depending on the APOE genotype. Comparison with prevalence and lifetime risk estimates of AD-type dementia suggests a 20- to 30-year interval between amyloid positivity and dementia, implying that there is a large window of opportunity to start preventive treatments.”

However, the authors point out that follow-up studies need to be conducted since not all people with amyloid pathology develop dementia in their lifetime, and not all people with a clinical diagnosis of Alzheimer’s dementia have amyloid pathology.

“Because of the uncertainty about whether and when an amyloid-positive individual without dementia will develop dementia, amyloid positivity in these individuals should not be equated with impending clinical dementia but rather be seen as a risk state,” they wrote. “Our prevalence rates can be used as an inexpensive and noninvasive approach to select persons at risk for amyloid positivity.”

The Innovative Medicines Initiative 2 (IMI 2) indicative topic text for Call 5 is now available, with heavy emphasis on Alzheimer’s Disease. The following topics are under consideration for inclusion in the call:

Patient perspective elicitation on benefits and risks of medicinal products from development through the entire life cycle, for integration into benefit risk assessments by regulators and health technology assessment bodies
Diabetic kidney disease biomarkers (DKD-BM)
Inflammation and Alzheimer’s disease (AD): modulating microglia function – focussing on TREM2 and CD33
Understanding the role of amyloid biomarkers in the current and future diagnosis and management of patients across the spectrum of cognitive impairment (from pre-dementia to dementia)
Evolving models of patient engagement and access for earlier identification of Alzheimer’s disease: phased expansion study
Apolipoprotein E (ApoE) biology to validated Alzheimer’s disease targets

Note: All information regarding future IMI Call topics is indicative and subject to change. Final information about future IMI Calls will be communicated after approval by the IMI Governing Board.

The National Institutes of Health, USA has released recommendations that provide a framework for a bold and transformative Alzheimer’s disease research agenda.

Developed at the February 2015 Alzheimer’s Disease Research Summit 2015: Path to Treatment and Prevention, the highly anticipated recommendations provide the wider Alzheimer’s research community with a strategy for speeding the development of effective interventions for Alzheimer’s and related dementias.

These recommendations call for a change in how the academic, biopharmaceutical and government sectors participating in Alzheimer’s research and therapy generate, share and use knowledge to propel the development of critically needed therapies.

In their latest brain imaging study on women at risk for Alzheimer’s disease, York University researchers have found deterioration in the pathways that serve to communicate signals between different brain regions needed for performing everyday activities such as driving a car or using a computer.

“We observed a relationship between the levels of deterioration in the brain wiring and their performance on our task that required simultaneous thinking and moving; what we see here is a result of communication failure,” explains Professor Lauren Sergio in the School of Kinesiology & Health Science.

In an interview, Sergio in whose lab the study was conducted, says the findings also suggest that their computerized, easily-administered task that the study participants performed, can be used to test those at risk for Alzheimer’s disease to flag early warning signs. “The test is a clinically feasible substitute to the more involved braining imaging tasks that people don’t, or can’t, have done routinely.”

The study, Diffusion Tensor Imaging Correlates of Cognitive-Motor Decline in Normal Aging and Increased Alzheimer’s Disease Risk, recently published in the Journal of Alzheimer’s Disease, was conducted on 30 female participants of whom 10 were in their mid-20s. The rest were in their 50s or older, with half of them at high risk for Alzheimer’s disease.

“We decided to focus this study on women, as there is higher prevalence in this group, and also women who carry the ApoE4 gene are more vulnerable to the degradation of white matter,” notes PhD candidate Kara Hawkins who led the study, adding that the genetic risk factor for Alzheimer’s disease was one of the traits tested for in the current study.

“We scanned the brains of the participants, aiming to see if the impaired cognitive-motor performance in the high risk group was related to brain alterations over and above standard aging changes,” Hawkins adds.

According to the researchers, the big question ahead is ‘what can be done to prevent a decline in function of a person’s brain showing signs of communication problems.’ And the answer they are exploring is in finding ways to use these thinking and moving tasks in a proactive way, as part of a game-like cognitive-motor integration training method

Source: News-Medical.net

GAP, initiated by the New York Academy of Sciences and Global CEO Initiative, is moving one step closer to reaching its goal of establishing a global, trial-ready platform for Alzheimer’s disease.

The Global Alzheimer’s Platform (GAP) and the Innovative Medicines Initiative (IMI) announced today that they will sign a Memorandum of Understanding (MOU) to accelerate Alzheimer’s drug development by building a global, standing, trial-ready platform for Alzheimer’s drug development.

The collaboration represents a significant commitment to work together to recruit patients for clinical trials, to create a high-performing clinical trial system, and to develop a standing adaptive protocol to test new molecules quickly, and move those with promise into later stage development.

Source: New York Academy of Sciences

Three leading research funders from the UK and North America have joined forces to launch a new global initiative called MEND or, MEchanisms of cellular death in NeuroDegeneration, with a fund of $1.25 million USD for targeted research into brain diseases that cause dementia, such as Alzheimer’s.

Alzheimer’s Research UK, the Alzheimer’s Association based in the U.S. and the Weston Brain Institute in Canada, whose participation in MEND is funded by Selfridges, announce the collaboration in response to the G7 health leaders’ commitment to collectively and significantly increase funding for dementia research, as announced at their December 2013 summit. G7 health leaders met in Bethesda, Maryland (U.S.A), last week to review progress on their goal to identify a cure or disease-modifying treatment by 2025.

MEND is open to applications from scientists around the globe, and researchers will be encouraged to collaborate on projects, sharing knowledge and resources in order to speed up progress. It’s hoped the scheme will also help answer fundamental questions about the similarities and differences between different diseases, such as whether the underlying mechanisms that cause cell death differ from one disease to another, and why each disease affects different types.

Source: Medical News.net

According to a recent study from a team of researchers at Tel Aviv University, a mutation in a specific neuroprotective protein called ADNP has different expressions between males and females. This research adds new insights to what is currently known about the etiology of autism and Alzheimer’s disease. The results are published in the journal Translational Psychiatry.

Recent evidence suggests that ADNP has a neuroprotective effect in patients with autism spectrum disorder (ASD), and has also been found to be decreased in the serum of patients with Alzheimer’s disease (AD)

In the study entitled “Activity-dependent neuroprotective protein (ADNP) exhibits striking sexual dichotomy impacting on autistic and Alzheimer’s pathologies”, the research team found that the ADNP exhibits different activities in males and females, which implies that there are gender differences in the risk of developing certain diseases. While it has already been established that autism affects more males, and that Alzheimer’s disease tends to affect more females, these specific gender disparities remain minimally understood.

In a recent news release, Tel Aviv University’s Prof. Illana Gozes said, “If we understand how ADNP, an activity-related neuroprotective protein which is a major regulatory gene, acts differently in males and females, we can try to optimize drugs for potential future therapeutics to treat both autism and Alzheimer’s disease.”

Prof. Gozes and colleagues investigated gender differences in behavioral responses in mice with ADNP-altered and normal mice, to different cognitive challenges and social situations. The researchers observed learning and memory differences between female and male mice, especially in the hippocampus. The results indicate differences in ADNP expressions, which can result in ADNP-controlled autism and in genes that elevate one’s risk for Alzheimer’s disease.

“ADNP may be new to the world of autism, but I have been studying it for 15 years,” said Prof. Gozes. “Its gender-dependent expression changes male and female chemical tendencies toward different neurological disorders. Male and female mice may look the same and their brains may look the same, but they are not. When the expression of ADNP is different, it may cause different behaviors and different cognitive abilities. This study emphasizes the need to analyze men and women separately in clinical trials to find cures for diseases because they may respond differently.”

Source: Alzheimer’s News Today

Some cases of Alzheimer’s disease progress quickly, mimicking prion-based Creutzfeldt-Jakob disease (CJD). Many people with this form of Alzheimer’s are misdiagnosed, because clinicians have no reliable way to distinguish between the two disorders.

In the January 5 JAMA Neurology, researchers led by Isabelle Quadrio at Hospices Civils de Lyon, Bron, France, propose using levels of total prion protein (t-PrP) in cerebrospinal fluid (CSF) to differentiate CJD from AD. The authors found that people with prion disease had lower CSF levels of this protein than AD patients did. In a study of 209 patients with either disorder, t-PrP classified patients much more accurately than the currently accepted biomarker, 14-3-3 protein, they report. When they combined t-PrP with CSF tau, they correctly identified 96 percent of patients with atypical, fast-progressing AD in this study, as compared with 57 percent using 14-3-3 alone.

Source: AlzForum

In a pilot study, researchers at the Department of Psychiatry and Psychotherapy of the University Medical Center of Johannes Gutenberg University Mainz (JGU) have recently gained new insights into how it may in future be possible to treat patients with the currently most common form of dementia – Alzheimer’s disease.

It seems that a drug that is actually approved for treatment of the dermal disorder psoriasis stimulates the activity of the enzyme ADAM10 in the brain of Alzheimer’s patients. There is already good evidence from basic research that this enzyme should be capable of suppressing Alzheimer’s disease-related effects such as impaired cerebral function and that it thus might improve learning and memory capacity in patients.

The results of the related study have recently been published in the journal Neurology.

Source: Heathcanal