University experts spot early signs of Alzheimer’s

Early signs of Alzheimer’s disease can be detected years before diagnosis, according to researchers at Birmingham City University.

The study found that sufferers of a specific type of cognitive impairment have an increased loss of cells in certain parts of the brain, which can be vital in detecting which patients will progress to a diagnosis of Alzheimer’s.

A team of researchers from Birmingham City University (UK), in association with colleagues from Lanzhou University (China) and the Alzheimer’s Disease Neuroimaging Initiative, conducted a brain scan analysis over two years, of patients suffering from amnestic mild cognitive impairment (aMCI) – a condition involving the diminishing of cognitive abilities, from which 80% of patients progress to a diagnosis of Alzheimer’s.

Scans showed that the loss of grey matter in the left hemisphere of the brain was particularly widespread and degenerative for those patients at high risk of developing Alzheimer’s, compared with those with no active neurological disorders.

This region of the brain has been associated with language, decision making, expressing personality, executing movement, planning complex cognitive behaviour and moderating social behaviour. 

One of the researchers involved in the study, Professor Mike Jackson, from Birmingham City University, said: “Continuous loss of cells within the regions of the brain highlighted in this study should act as alarm bells for doctors, as they may indicate that the patient is on course to developing Alzheimer’s.”

The brains parahippocampal gyrus, a region which is known to be related to memory encoding and retrieval, was highlighted as an area that should be looked at carefully when examining brain scans to detect early signs of the disease.

Treating Alzheimer’s early is thought to be vital to prevent damage to memory and thinking. Although treatments are available to temporarily ease symptoms, there has been little in the way of success in slowing down the cognitive decline in patients with mild to moderate Alzheimer’s, which has been partly put down to the late timing of the diagnosis.

Experts at Birmingham City University hope that this study will aid other researchers to find an effective clinical treatment to delay the conversion to Alzheimer’s.

Inside the Minds of Murderers

Impulsive murderers much more mentally impaired than those who kill strategically

The minds of murderers who kill impulsively, often out of rage, and those who carefully carry out premeditated crimes differ markedly both psychologically and intellectually, according to a new study by Northwestern Medicine® researcher Robert Hanlon.

“Impulsive murderers were much more mentally impaired, particularly cognitively impaired, in terms of both their intelligence and other cognitive functions,” said Hanlon, senior author of the study and associate professor of clinical psychiatry and clinical neurology at Northwestern University Feinberg School of Medicine.

“The predatory and premeditated murderers did not typically show any major intellectual or cognitive impairments, but many more of them have psychiatric disorders,” he said.

Published online in the journal Criminal Justice and Behavior, the study is the first to examine the neuropsychological and intelligence differences of murderers who kill impulsively versus those who kill as the result of a premeditated strategic plan.

• Compared to impulsive murderers, premeditated murderers are almost twice as likely to have a history of mood disorders or psychotic disorders — 61 percent versus 34 percent.
• Compared to predatory murderers, impulsive murderers are more likely to be developmentally disabled and have cognitive and intellectual impairments — 59 percent versus 36 percent.
• Nearly all of the impulsive murderers have a history of alcohol or drug abuse and/or were intoxicated at the time of the crime — 93 percent versus 76 percent of those who strategized about their crimes.

Based on established criteria, 77 murderers from typical prison populations in Illinois and Missouri were classified into the two groups (affective/impulsive and premeditated/predatory murderers). Hanlon compared their performances on standardized measures of intelligence and neuropsychological tests of memory, attention and executive functions. He spent hours with each individual, administering series of tests to complete an evaluation. Hanlon has spent thousands of hours studying the minds of murderers through his research.

“It’s important to try to learn as much as we can about the thought patterns and the psychopathology, neuropathology and mental disorders that tend to characterize the types of people committing these crimes,” he said. “Ultimately, we may be able to increase our rates of prevention and also assist the courts, particularly helping judges and juries be more informed about the minds and the mental abnormalities of the people who commit these violent crimes.”

(Image: ALAMY)

Alzheimer’s and Low Blood Sugar in Diabetes May Trigger a Vicious Cycle

A new UC San Francisco-led study looks at the close link between diabetes and dementia, which can create a vicious cycle.

Diabetes-associated episodes of low blood sugar may increase the risk of developing dementia, while having dementia or even milder forms of cognitive impairment may increase the risk of experiencing low blood sugar, according to the study published online Monday in JAMA Internal Medicine.

Researchers analyzed data from 783 diabetic participants and found that hospitalization for severe hypoglycemia among the diabetic, elderly participants in the study was associated with a doubled risk of developing dementia later. Similarly, study participants with dementia were twice as likely to experience a severe hypoglycemic event.

The study results suggest some patients risk entering a downward spiral in which hypoglycemia and cognitive impairment fuel one another, leading to worse health, said Kristine Yaffe, MD, senior author and principal investigator for the study, and a UCSF professor of psychiatry, neurology and epidemiology based at the San Francisco Veterans Affair Medical Center.

“Older patients with diabetes may be especially vulnerable to a vicious cycle in which poor diabetes management may lead to cognitive decline and then to even worse diabetes management,” she said.

Cognitive Function a Factor in Managing Diabetes

The researchers analyzed hospital records of patients from Memphis and Pittsburgh, ages 70 to 79 at the time of enrollment, who participated in the federally funded Health, Aging and Body Composition (Health ABC) study, begun in 1997. The UCSF results are based on an average of 12 years of follow-up study. Participants in the Health ABC study periodically underwent tests to measure cognitive function.

Nearly half of participants included in the newly published analysis were black, and the rest were white. None had dementia at the start of the study, and all either had diabetes at the beginning of the study or were diagnosed during the course of the study.

“Individuals with dementia or even those with milder forms of cognitive impairment may be less able to effectively manage complex treatment regimens for diabetes and less able to recognize the symptoms of hypoglycemia and to respond appropriately, increasing their risk of severe hypoglycemia,” Yaffe said. “Physicians should take cognitive function into account in managing diabetes in elderly individuals.”

Certain medications known to carry a higher risk for hypoglycemia — such as insulin secretagogues and certain sulfonylureas — may be inappropriate for older adults with dementia or who are at risk for cognitive impairment, according to Yaffe.

Previous studies in which researchers investigated hypoglycemia and cognitive function have had inconsistent findings. A strength of the current study is that individuals were tracked from baseline over a relatively long time, and the older age of participants may also have been a factor in the highly statistically significant outcome, Yaffe said.

B vitamins could delay dementia

Despite spending billions of dollars on research and development, drug companies have been unable to come up with effective treatments for dementia and Alzheimer’s Disease (AD). Now, A. David Smith at the University of Oxford and his colleagues have discovered that, in some patients experiencing mild cognitive impairment (MCI), a cocktail of high-dose B vitamins could prevent gray matter loss associated with progression to AD. The study appears in the Proceedings of the National Academy of Sciences.

The World Health Organization predicts that between 2010 and 2050 the number of dementia cases will increase from 26 million to 115 million worldwide. Although there is an urgent demand for treatment, pharmaceutical companies have been unable to develop drugs that will delay or cure dementia. So far, approved drugs merely ease symptoms.

Smith and his team wanted to see if B vitamins reduced the risk of AD by lowering total homocysteine (tHcy) levels. There is a positive correlation between high tHcy levels and risk of cognitive impairment and AD.

The researchers studied 156 subjects over 70 in Oxford, England who suffered from MCI. The subjects received either a placebo or a high-dose B vitamin cocktail consisting of 20 milligrams of vitamin B6, 0.5 milligrams of vitamin B12 and 0.8 milligrams of folic acid.

Over a two-year period, subjects in both the experimental and control groups lost gray matter in the medial temporal, lateral temporoparietal and occipital regions and in the anterior and posterior cingulate cortex.

However, those receiving B vitamin treatment experienced significantly less atrophy in regions of the brain most affected in people with AD and people with MCI who go on to develop AD. These include the bilateral hippocampus, the parahippocampal gyrus, the retrosplenial precuneus, the lingual gyrus, the fusiform gyrus and the cerebellum. The placebo group experienced a 3.7 percent loss of gray matter in these regions, compared with a 0.5 percent loss among the experimental group.

When they looked at baseline tHcy levels, Smith and his colleagues found that B-vitamin treatment did not significantly reduce gray matter atrophy among subjects with tHcy levels below the median. The B-vitamin cocktail did have a significant effect on high-tHcy participants: those receiving the cocktail experienced only a 0.6 percent loss of gray matter, while high-tHcy participants in the placebo group experienced a 5.2 percent loss.

The team found a correlation between gray matter loss and worsening of scores on tests that measure cognitive function.

A causal Bayesian network analysis showed that B vitamins lower tHcy levels. This decreases gray matter atrophy, which delays cognitive decline.

Forget about plaque when diagnosing Alzheimer’s Disease

An Australian study has shown that plaque, long considered to be the hallmark of Alzheimer’s disease, is one of the last events to occur in the Alzheimer’s brain. This finding will impact the current debate about how best to diagnose and treat Alzheimer’s disease.

PhD student Amanda Wright and Dr Bryce Vissel from Sydney’s Garvan Institute of Medical Research studied a mouse model of Alzheimer’s disease in order to identify early versus late disease mechanisms and markers.

The data, published online today in the journal PLOS ONE, suggest that plaques occur long after memory loss, so may not be a useful early pathological marker for Alzheimer’s disease.

The Investigators found that significant nerve cell loss and a range of brain pathologies, including inflammation, began at the same time as subtle memory problems appeared, early in the disease process. Plaques occurred much later, well after significant memory loss.

“Ever since Alois Alzheimer first described this disease in 1906, plaque has been regarded as the definitive Alzheimer’s diagnosis,” said project leader Dr Vissel.

“Just last year, the first ever method of plaque detection through positron emission tomography (PET) was introduced into the clinic to assist in the diagnosis of Alzheimer’s disease – precisely because plaque is regarded as the conclusive marker for Alzheimer’s disease. Our study suggests that this method may not be accurate in earlier disease stages.”

Dr Vissel said that many billions of dollars have been spent around the world in trying to develop markers and drugs to block the development of plaque. Several drug trials based on this idea have failed recently.

“Our study supports the increasingly common view that treatment should start much earlier in the disease process. It also suggests that brain inflammation and cell loss may be an earlier indicator of disease pathology than plaque and an alternative target for treatment.”

“In addition, what’s coming out in various studies is that mild cognitive impairment may be another early predictor of Alzheimer’s. This seems to fit perfectly with our findings, which show mild memory loss and behavioural changes at an early stage before plaque appears.”

“I can see that the development of some clever learning and language tests to test for early signs of cognitive impairment will be an important indicator of dementia, when combined with a range of yet to be developed tests.”

(Image: Getty Images)

Study examines change in cognitive function following physical, mental activity in older adults

A randomized controlled trial finds that 12 weeks of physical plus mental activity in inactive older adults with cognitive complaints was associated with significant improvement in cognitive function but there was no difference between intervention and control groups, according to a report published Online First by JAMA Internal Medicine, a JAMA Network publication.

An epidemic of dementia worldwide is anticipated during the next 40 years because of longer life expectancies and demographic changes. Behavioral interventions are a potential strategy to prevent or delay dementia in asymptomatic individuals, but few randomized controlled trials have studied the effects of physical and mental activity together, according to the study background.

"We found that cognitive scores improved significantly over the course of 12 weeks, but there were no significant differences between the intervention and active control groups. These results may suggest that in this study population, the amount of activity is more important than the type of activity, because all groups participated in both mental activity and exercise for [60 minutes/per day, three days/per week] for 12 weeks. Alternatively, the cognitive improvements observed may be due to practice effects," the authors note.

The study by Deborah E. Barnes, Ph.D., M.P.H., of the University of California, San Francisco, and colleagues included 126 inactive, community-dwelling older adults with cognitive complaints. All the individuals engaged in home-based mental activity (1 hour/per day, 3 days/per week) plus class-based physical activity (1 hour/per day, 3 days/per week) for 12 weeks and were assigned to either mental activity intervention (MA-I, intensive computer work); or mental activity control (MA-C, educational DVDs) plus exercise intervention (EX-1, aerobic) or exercise control (EX-C, stretching and toning). The study design meant there were four groups: MA-I/EX-I, MA-I/EX-C, MA-C/EX-1 and MA-C/EX-C.

Global cognitive scores improved significantly over time but did not differ between groups in the comparison between MA-I and MA-C (ignoring exercise), the comparison between EX-I and EX-C (ignoring mental activity), or across all four randomization groups, according to the study results.

"The prevalence of cognitive impairment and dementia are projected to rise dramatically during the next 40 years, and strategies for maintaining cognitive function with age are critically needed. Physical or mental activity alone result in small, domain-specific improvements in cognitive function in older adults; combined interventions may have more global effects," the study concludes.

(Image: Getty Images)

New mechanism for long-term memory formation discovered

UC Irvine neurobiologists have found a novel molecular mechanism that helps trigger the formation of long-term memory. The researchers believe the discovery of this mechanism adds another piece to the puzzle in the ongoing effort to uncover the mysteries of memory and, potentially, certain intellectual disabilities.

In a study led by Marcelo Wood of UC Irvine’s Center for the Neurobiology of Learning & Memory, the team investigated the role of this mechanism – a gene designated Baf53b – in long-term memory formation. Baf53b is one of several proteins making up a molecular complex called nBAF.

Mutations in the proteins of the nBAF complex have been linked to several intellectual disorders, including Coffin-Siris syndrome, Nicolaides-Baraitser syndrome and sporadic autism. One of the key questions the researchers addressed is how mutations in components of the nBAF complex lead to cognitive impairments.

In their study, Wood and his colleagues used mice bred with mutations in Baf53b. While this genetic modification did not affect the mice’s ability to learn, it did notably inhibit long-term memories from forming and severely impaired synaptic function.

“These findings present a whole new way to look at how long-term memories form,” said Wood, associate professor of neurobiology & behavior. “They also provide a mechanism by which mutations in the proteins of the nBAF complex may underlie the development of intellectual disability disorders characterized by significant cognitive impairments.”

How does this mechanism regulate gene expression required for long-term memory formation? Most genes are tightly packaged by a chromatin structure – chromatin being what compacts DNA so that it fits inside the nucleus of a cell. That compaction mechanism represses gene expression. Baf53b, and the nBAF complex, physically open the chromatin structure so specific genes required for long-term memory formation are turned on. The mutated forms of Baf53b did not allow for this necessary gene expression.

“The results from this study reveal a powerful new mechanism that increases our understanding of how genes are regulated for memory formation,” Wood said. “Our next step is to identify the key genes the nBAF complex regulates. With that information, we can begin to understand what can go wrong in intellectual disability disorders, which paves a path toward possible therapeutics.”

Findings appear online today in Nature Neuroscience.