Category Archives: Alzheimer’s Disease

Novel Blood Test Shows Promise for Early Diagnosis of Alzheimer’s Disease

August 27, 2020

Alzheimer’s disease (AD) is a debilitating and incurable condition affecting approximately 6 million Americans aged 65 and older. As the number of AD cases in the United States is projected to reach an estimated 14 million by the year 2050, there is a pressing need for effective prevention therapies. Currently, there are limitations in diagnostic testing methods for Alzheimer’s disease; to date, the diagnosis of AD has been largely based on amyloid plaques and tau tangles identified in the brain postmortem.

Emerging evidence from Lund University evaluated the potential profound impact on Alzheimer’s research and care an inexpensive and accessible diagnostic test for the presence of plaques and tangles would have. In the recent study, researchers demonstrate the great promise of a novel blood test in discriminating between persons with and without AD as well as identifying the disease in individuals at known genetic risk as early as 20 years before onset.

The large international study was recently published in the Journal of the American Medical Association (JAMA) and reveals that measurements of phospho-tau217 (p-tau217) could help medical professionals accurately identify symptoms of Alzheimer’s in living patients.

Identifying Alzheimer’s Disease 

Researchers in Arizona, Sweden, and Colombia investigated the discriminative accuracy of plasma phospho-tau217 at differentiating Alzheimer’s disease from other neurodegenerative disorders. To do so, the study’s authors evaluated a new p-tau217 blood test administered in 1,402 cognitively impaired and unimpaired participants. Subjects included 81 participants from Arizona’s Banner Sun Health Research Institute Brain Donation program, 699 patients from the Swedish BioFINDER Study, and 522 Colombian autosomal dominant AD-causing mutation carriers and non-carriers.

P-tau217 Accurately Distinguishes Risk

The cross-sectional study found that plasma p-tau217 discriminated Alzheimer’s disease from other neurodegenerative diseases with significantly more accuracy than established AD plasma- and MRI-based biomarkers.

In the Arizona cohort, the novel blood test successfully discriminated between brain donors with and without the subsequent diagnosis of “intermediate or high likelihood of Alzheimer’s” with 89% accuracy. Meanwhile, in participants with and without a diagnosis of “high likelihood” the assay was 98% accurate. Higher p-tau217 measures were associated with increased brain tangle counts only in participants with present amyloid plaques.

Within the Swedish cohort, the assay discriminated between persons with clinically diagnosed Alzheimer’s and other neurodegenerative diseases with 96% accuracy, similar to tau PET scans and CSF biomarkers and better than several other blood tests and MRI measurements. Further, it distinguished between patients with and without an abnormal tau PET scan with up to 93% accuracy.

Finally, in the Colombian cohort, the blood test was able to distinguish between mutation carriers and non-carriers 20 years before their estimated age of onset of mild cognitive impairment. For all of the analyses performed, p-tau217 was found to outperform p-tau181 – a similar component of tau tangles and blood test – as well as several other studied assays; its performance did not differ significantly from that of key CSF- or PET-based measures.

In recent years, much progress has been made in the development of blood tests for Alzheimer’s disease. Although the plasma p-tau217 was found to discriminate AD from other neurodegenerative disease, additional research is needed to validate these findings in larger and more diverse cohorts in order to both optimize the blood test and determine its potential role in the clinical setting.

”The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer’s,” lead author Oskar Hansson, MD, PhD, told Science Daily.“While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting.”

Ketone-Rich Diets May Reduce Alzheimer’s Disease Risk

February 19, 2020

In the early stages of development, Alzheimer’s disease (AD) causes overactive brain functioning, potentially as a result of the loss of inhibitory – GABAergic – interneurons that control the signaling of other neurons in the circuit. Interneurons require more energy compared with other neurons, which makes them more susceptible to degeneration upon encountering the Alzheimer’s disease protein – amyloid beta. Research has shown the negative impact of amyloid beta interaction , revealing its ability to damage mitochondria by interfering with SIRT3 – a protective protein.

Impaired mitochondrial function and abnormal neuronal network activity are thought to be some of the early signs of the development of Alzheimer’s disease, however, how mitochondrial alterations contribute to the abnormal activity in neural circuits and their connection to AD remains unknown.

SIRT3 in Mice with Alzheimer’s Disease 

In a recent study published in the Journal of Neuroscience, Aiwu Chang, PhD, and her colleagues investigated the function of the mitochondrial protein by genetically reducing the levels of SIRT3 in mouse models of Alzheimer’s disease. Per their findings, mice with low levels of SIRT3 experienced a significantly higher mortality rate, more violent seizures, and increased interneuron death compared with mice from the standard Alzheimer’s disease model as well as the control group. Both male and female mice were observed to die prematurely before 5 months of age.

On the other hand, mice with reduced levels of SIRT3 who consumed a ketone-rich diet experienced fewer seizures and were less likely to die. Consuming the fatty acid also increased levels of SIRT3 in these mice.  “When comparing male mice among different genotypes, SIRT3 haploinsufficiency renders GABAergic interneurons in the cerebral cortex vulnerable to degeneration and associated neuronal network hyperexcitability,” researchers wrote.

In short, SIRT3 proteins work to preserve GABAergic interneurons and protect cerebral circuits against hyperexcitability; this neuroprotective mechanism can potentially be reinforced by dietary ketone intake.

Ketone Consumption for Risk Reduction

The latest findings implicate that the consumption of ketones may be a way of protecting interneurons and delaying the progression of Alzheimer’s disease. By preserving mitochondrial function, SIRT3 protects interneurons against amyloid beta-induced dysfunction ad degeneration in mice with Alzheimer’s disease. According to Dr. Chang and her team, “the neuronal network dysfunction that occurs in Alzheimer’s disease can be partially reversed by physiological, dietary, and pharmacological interventions to increase SIRT3 expression and enhance the functionality of GABAergic interneurons.”

Due to the growing popularity of the ketogenic diet – which can support weight loss, diabetes management, and several other health conditions – there is an increased awareness and availability of ketone-rich foods. Limiting carbohydrate consumptions and incorporating ketone-rich foods such as seafood, low carb vegetables, high-quality meat and poultry, and eggs into the diet may prove to have neuroprotective effects.

The study’s findings implicate the potential benefit of ketone consumption; however, the results need to be verified in human studies before any recommendations can be made. Further research is necessary to determine whether a ketogenic diet in humans may reduce Alzheimer’s disease risk and to what degree.

Can a Healthy Lifestyle Reduce Genetic Risk for Dementia?

February 8, 2020

A combination of genetic and lifestyle factors can play a role in determining an individual’s risk of Alzheimer’s disease and other types of dementia. Although most cases occur in older adults in whom multiple genes influence overall risk, high levels of LDL cholesterol, diabetes, atherosclerosis, and other health factors can further elevate risk. While some risk factors may be difficult to mitigate, others are easily modifiable – for example, weight and lipid management through a combination of lifestyle changes.

A growing body of evidence suggests that individuals who lead a healthy lifestyle – avoid smoking tobacco, engage in regular physical activity, and consume a health diet – have a lower risk of developing dementia. Previous research has investigated the impact of lifestyle factors on many other health conditions such as cardiovascular disease, however, the extent to which these variables can influence dementia risk is unknown. A new study published online in JAMA, uses data from a large population-based cohort to investigate whether adherence to a healthy lifestyle can offset existing genetic risk for dementia.

Association of Lifestyle Habits with Dementia Risk

Led by Ilianna Lourida, PhD from the University of Exeter Medical School, a team of researchers conducted a retrospective cohort study of nearly 200,000 European adults aged 60 and above to investigate whether a healthy lifestyle is associated with a reduced risk of dementia – regardless of genetic factors. At baseline, none of the participants had cognitive impairment or dementia. The main outcome was the incidence of all-cause dementia identified through hospital records.

Researchers calculated a polygenic risk score comprised of common genetic variants linked to Alzheimer’s disease and dementia risk, as well as a weighted healthy lifestyle score – which included smoking status, physical activity levels, dietary patterns, and alcohol consumption.

Healthy Lifestyle May Reduce Dementia Incidence

A total of 196,383 participants with a mean age of 64.1 were followed for a median of 8 years, during which there were 1,769 cases of incident all-cause dementia. Overall, over 68% of the cohort had followed a healthy lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Researchers found that 20% of individuals had high polygenic risk scores, 60% had intermediate-risk scores, and 20% had low-risk scores.

Of those with a high genetic risk, 1.23% developed dementia, compared with 0.63% of participants with low genetic risk. Meanwhile, participants with both a high genetic risk and unfavorable lifestyle developed dementia at a rate of 1.78% compared with 0.56% of participants with low genetic risk and a favorable lifestyle. Researchers found no significant interaction between genetic risk and lifestyle factors. Among individuals with high genetic risk, 1.13% of those leading a healthy lifestyle developed dementia, in comparison with the 1.78% with unfavorable lifestyle.

Risk Reduction

Dr. Lourida and her team found that an unfavorable lifestyle coupled with high genetic risk was significantly associated with a higher risk for developing dementia in older adults without pre-existing cognitive impairment. Meanwhile, a healthy lifestyle was associated with a lower dementia risk even among participants with a high genetic risk. While there was no significant interaction between genetic risk and a healthy lifestyle, a favorable lifestyle was associated with reduced dementia risk regardless of genetic factors.

Overall, the authors found an absolute risk reduction for dementia among the high genetic risk group of 0.65% associated with leading a favorable lifestyle.

The study’s authors acknowledged the trial’s limitations. Firstly, the lifestyle score used in calculations was not independently validated to indicate a high-risk lifestyle outside of trial conditions. Furthermore, there was a possibility of unmeasured confounding and reverse causation. In addition, lifestyle factors were self-reported and some cases of dementia might not have been recorded in medical records or death registers. Nonetheless, the study expands on current knowledge of neurodegenerative diseases and their connection to lifestyle choices.

“This risk reduction implies that, if lifestyle is causal, 1 case of dementia would be prevented for each 121 individuals per 10 years with high genetic risk who improved their lifestyle from unfavorable to favorable,” authors wrote. Aside from the many mental and physical health benefits associated with leading a health-conscious lifestyle, doing so may also contribute to lowering dementia risk by reducing oxidative damage, having anti-thrombotic and anti-inflammatory effects as well as increasing cerebral blood flow. Thus, it is important to encourage patients to follow a favorable lifestyle and support lifestyle interventions when necessary, especially in cases of high genetic risk.