Tag Archives: Risk Factor

A gene associated with Alzheimer’s disease and recovery after brain injury may show its effects on the brain and thinking skills as early as childhood, according to a study published in Neurology.

Prior studies showed that people with the epsilon(ε)4 variant of the apolipoprotein-E gene are more likely to develop Alzheimer’s disease than people with the other two variants of the gene, ε2 and ε3.

For the study, 1,187 children ages three to 20 years had genetic tests and brain scans and took tests of thinking and memory skills. The children had no brain disorders or other problems that would affect their brain development, such as prenatal drug exposure.

Each person receives one copy of the gene (ε2, ε3 or ε4) from each parent, so there are six possible gene variants: ε2ε2, ε3ε3, ε4ε4, ε2ε3, ε2ε4 and ε3ε4.

The study found that children with any form of the ε4 gene had differences in their brain development compared to children with ε2 and ε3 forms of the gene. The differences were seen in areas of the brain that are often affected by Alzheimer’s disease. In children with the ε2ε4 genotype, the size of the hippocampus, a brain region that plays a role in memory, was approximately 5 percent smaller than the hippocampi in the children with the most common genotype (ε3ε3). Children younger than 8 and with the ε4ε4 genotype typically had lower measures on a brain scan that shows the structural integrity of the hippocampus.

“These findings mirror the smaller volumes and steeper decline of the hippocampus volume in the elderly who have the ε4 gene,” said study author Linda Chang, MD, of the University of Hawaii in Honolulu.

In addition, some of the children with ε4ε4 or ε4ε2 genotype also had lower scores on some of the tests of memory and thinking skills. Specifically, the youngest ε4ε4 children had up to 50 percent lower scores on tests of executive function and working memory, while some of the youngest ε2ε4 children had up to 50 percent lower scores on tests of attention. However, children older than 8 with these two genotypes had similar and normal test scores compared to the other children.

Limitations of the study include that it was cross-sectional, meaning that the information is from one point in time for each child, and that some of the rarer gene variants, such as ε4ε4 and ε2ε4, and age groups did not include many children.

While strokes are known to increase risk for dementia, much less is known about diseases of large and small blood vessels in the brain, separate from stroke, and how they relate to dementia. Diseased blood vessels in the brain itself, which commonly is found in elderly people, may contribute more significantly to Alzheimer’s disease dementia than was previously believed, according to new study results published in The Lancet Neurology.

“Cerebral vessel pathology might be an under-recognized risk factor for Alzheimer’s disease dementia,” the researchers wrote.

The study analyzed medical and pathologic data on 1,143 older individuals who had donated their brains for research upon their deaths, including 478 (42 percent) with Alzheimer’s disease dementia. Analyses of the brains showed that 445 (39 percent) of study participants had moderate to severe atherosclerosis — plaques in the larger arteries at the base of the brain obstructing blood flow — and 401 (35 percent) had brain arteriolosclerosis — in which there is stiffening or hardening of the smaller artery walls.

The study found that the worse the brain vessel diseases, the higher the chance of having dementia, which is usually attributed to Alzheimer’s disease. The increase was 20 to 30 percent for each level of worsening severity. The study also found that atherosclerosis and arteriolosclerosis are associated with lower levels of thinking abilities, including in memory and other thinking skills, and these associations were present in persons with and without dementia.

The study examined which cognitive difficulties are caused by vessel diseases and whether vessel disease and Alzheimer’s are more destructive in tandem than they would be alone. An editorial in The Lancet Neurology that accompanied the study findings noted that while other studies have indicated that proactive measures like eating a selective diet and getting regular exercise might protect people against getting Alzheimer’s, those interventions might actually be acting on non-Alzheimer’s disease processes, such as cerebrovascular disease.

The participants in the study published in Lancet Neurology came from two (RADC) cohort studies, the Religious Orders Study and the Rush Memory and Aging Project, which have followed people older than 65, in their communities, for more than two decades. Participants receive annual health assessments and agree to donate their brains for research upon their deaths. The Lancet Neurology study used clinical data gathered from participants from 1994 to 2015, and pathologic data obtained from examination of the brains donated for autopsy, and used regression analyses to determine the odds of Alzheimer’s dementia and levels of cognitive function, for increasing levels of brain vessel diseases.

Paper: Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study”
Source: Reprinted from materials provided by Rush University Medical Center.

 

Acta Neuropathologica“Inside out: the role of nucleocytoplasmic transport in ALS and FTLD” has been published in Acta Neuropathologica. This research was supported in part by JPND through the STRENGTH and RiMod-FTD projects, selected under the 2012 risk factors call.

Cerebrospinal fluid soluble TREM2 in aging and Alzheimer’s disease” has been published in Alzheimer’s Research & Therapy. This research was supported in part by JPND through the APGeM project, selected in the 2012 risk factors call.

A new paper titled “C9orf72 is differentially expressed in the central nervous system and myeloid cells and consistently reduced in C9orf72, MAPT and GRN mutation carriers” has been published in Acta Neuropathologica Communications. It was partly funded by JPND through the RiMod-FTD project, which was selected for support in the 2012 call for research projects for the identification of genetic, epigenetic and environmental risk and protective factors for neurodegenerative diseases.

Scientists have revealed that protein clumps associated with Alzheimer’s disease are also found in the brains of people who have had a head injury.

Although previous research has shown that these clumps, called amyloid plaques, are present shortly after a brain injury – this study shows the plaques are still present over a decade after the injury.

The findings may help explain why people who have suffered a serious brain injury appear to be at increased risk of dementia. Although extensive research now suggests major head injury increases dementia risk in later life, scientists do not know the biological changes that cause this effect.

In the research, published in the journal Neurology, the team studied nine patients with moderate to severe traumatic brain injuries. Many had sustained these in road traffic accidents, such as being hit by a car, between 11 months to 17 years prior to the study. The patient underwent a brain scan that used a technique that allows scientists to view amyloid plaques. These proteins are thought to be a hallmark of Alzheimer’s disease, and their formation may trigger other changes that lead to the death of brain cells.

The team also scanned the brains of healthy volunteers, and people with Alzheimer’s disease. The patients with head injury were found to have more amyloid plaques than the healthy volunteers, but fewer than those with Alzheimer’s disease.

In the head injury patients, the amyloid plaques were found to be centred mainly in two brain areas: the posterior cingulate cortex – a highly active area in the centre of the brain involved in controlling attention and memory, and the cerebellum – a region at the base of the brain involved in motor control and coordination.

In a second part of the study, the team assessed damage to so-called white matter. This is the ‘wiring’ of the brain, and enables brain cells to communicate with each other. The results showed that amyloid plaque levels in the posterior cingulate cortex were related to the amount of white matter damage, suggesting that injury to the brain’s wiring may be linked to the formation of amyloid plaques.

Source: Imperial College London

Men taking androgen deprivation therapy (ADT) for prostate cancer were almost twice as likely to be diagnosed with Alzheimer’s disease in the years that followed than those who didn’t undergo the therapy, an analysis of medical records from two large hospital systems has shown. Men with the longest durations of ADT were even more likely to be diagnosed with Alzheimer’s disease.

The findings, published in the Journal of Clinical Oncology, do not prove that ADT increases the risk of Alzheimer’s disease. But the authors say they clearly point to that possibility, and are consistent with other evidence that low levels of testosterone may weaken the aging brain’s resistance to Alzheimer’s.

For the study, researchers evaluated two large sets of medical records, one from the Stanford health system and the other from Mt. Sinai Hospital in New York City. The researchers scanned the records of 1.8 million patients from Stanford Health Care, and, through a prior institutional research agreement, 3.7 million patients from Mount Sinai Hospital.

Among this cohort, they identified about 9,000 prostate cancer patients at each institution, 16,888 of whom had non-metastatic prostate cancer. A total of 2,397 had been treated with androgen deprivation therapy. The researchers compared these ADT patients with a control group of non-ADT prostate cancer patients, matched according to age and other factors.

Using two different methods of statistical analysis, the team showed that the ADT group, compared to the control group, had significantly more Alzheimer’s diagnoses in the years following the initiation of androgen-lowering therapy. By the most sophisticated measure, members of the ADT group were about 88 percent more likely to get Alzheimer’s.

Source: Penn Medicine

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 recent studies have investigated the direct links and associations between depression and Parkinson’s Disease

A longitudinal study from Sweden investigated the long-term risk of Parkinson disease (PD) after depression and evaluated potential confounding by shared susceptibility to the two diagnoses.

Published in the journal Neurology, this study demonstrated a time-dependent effect, dose-response pattern for recurrent depression, and lack of evidence for co-aggregation among siblings which together indicate a direct association between depression and subsequent PD. Given that the association was significant for a follow-up period of more than two decades, depression may be a very early pro-dromal symptom of PD, or a causal risk factor.

The effects of anti-depressive treatments for Parkinson’s Disease were also recently reviewed in the journal Parkinsonism & Related Disorders.  The associated meta-analysis in the study demonstrates that pharmacologic treatment with antidepressant medications, specifically the selective serotonin reuptake inhibitors (SSRIs), and behavioral interventions (CBT) significantly improved depression among Parkinson’s disease patients.

The authors examined trials assessing treatment for depression in Parkinson’s disease (dPD) and found that:

  • SSRIs demonstrate significant improvement in depressive symptoms.
  • Cognitive behavioral therapy (CBT) shows a substantial effect in dPD treatment.
  • Evidence of efficacy of both SSRIs and CBT is provided, at least on the short term.

Cohort Study:  Depression and subsequent risk of Parkinson disease – A nationwide cohort study. Gustaffssonn et al., Neurology.  Published online before print May 20, 2015, doi: 10.1212/WNL.0000000000001684

Antidepressive treatments for Parkinson’s disease: A systematic review and meta-analysis
Emily Bomasang-Layno, et al., Parkinsonism & Related Disorders, Available online 16 May 2015