Wellderly Study Suggests Link Between Genes That Protect Against Cognitive Decline and Overall Healthy Aging

An eight-year-long accrual and analysis of the whole genome sequences of healthy elderly people, or “Wellderly,” has revealed a higher-than-normal presence of genetic variants offering protection from cognitive decline, researchers from the Scripps Translational Science Institute (STSI) reported today in the journal Cell.

The initial findings from the Wellderly Study suggest a possible link between long-term cognitive health and protection from chronic diseases, including cancer, heart disease and diabetes, which account for 90 percent of all deaths in the United States and other industrialized nations and more than 75 percent of health care costs.

“The Wellderly, as we’ve defined, are exceptional individuals who live into their ninth decade and beyond without developing a significant chronic medical condition,” said STSI Director Eric Topol, M.D., who is one of the study’s senior authors. “Our findings indicate that protection from cognitive decline is associated, not necessarily cause and effect, with healthspan. Since healthspan is woefully understudied, much more work in large numbers of individuals across all ancestries is desperately needed. For this reason, we have made all the genomic data available to the research community and public to help spawn further research.”

Results of the Wellderly Study were published online today by Cell. The report also will appear in the journal’s May print edition.

STSI is a National Institutes of Health-sponsored site led by Scripps Health in collaboration with The Scripps Research Institute. This innovative research partnership is leading the effort to translate wireless and genetic medical technologies into high-quality, cost-effective treatments and diagnostics for patients.

STSI researchers launched the Wellderly Study in 2007 in hopes of unlocking the genetic secrets behind lifelong health. The ongoing project has enrolled more than 1,400 people from across the country ranging in age from 80 to 105 who have not developed any chronic medical conditions or diseases including cancer, stroke, Alzheimer’s, Parkinson’s disease, diabetes and heart attack.

“This study is exciting because it is the first large one using genetic sequencing to focus on health,” said Stanford University Department of Genetics Chairman Michael Snyder, Ph.D., who was not involved with the research. “Most of the world’s scientists are studying disease, but what we really want to understand is what keeps us healthy. That is what the Wellderly Study is all about.”

John Rawlings, 90, of San Diego is one of the study’s participants. The Indiana native and World War II veteran started playing softball in his 70s and was inducted into the National Senior Softball Hall of Fame in 2009. He also is an avid reader.

“When I turned 90, they said, ‘Let’s have a big party,'” Rawlings said. “I told them, ‘You’d better wait until I turn 100.'”

For the study, researchers sequenced the whole genomes of 600 study participants and compared their DNA with genetic data gathered from 1,507 adults by Inova Translational Medicine Institute as part of a separate study. The ITMI cohort represented the general population. All of the genomes were mapped using the Complete Genomics sequencing platform.

After filtering to control for ethnic differences and blood relatedness, downstream DNA analyses were conducted on the genomes of 511 Wellderly individuals and 686 ITMI individuals. Researchers ended up analyzing 24,205,551 individual gene variants in both groups.

The Wellderly group had a significantly lower genetic risk for Alzheimer’s and coronary artery disease, researchers found. However, no difference was found between the two groups in genetic risk for cancer, stroke or type 2 diabetes, suggesting protective behaviors or other genetic characteristics might be at play among the Wellderly.

“We didn’t find a silver bullet for healthy longevity,” said Ali Torkamani, Ph.D., director of genome informatics at STSI and one of the study’s co-authors. “Instead, we found weaker signals among common as well as rare variant sites, which collectively suggest that protection against cognitive decline contributes to healthy aging.”

Of particular interest was a group of ultra-rare coding variants found among 10 Wellderly individuals in the COL25A1 gene, which encodes for a major component of amyloid plaques found in the brains of Alzheimer’s disease patients. None of the coding variants were found among the ITMI individuals.

“Those gene variants might offer a pathway for the development of new treatments for Alzheimer’s,” Torkamani said.

“For many decades, we have searched for the genetic causes of disease in sick individuals,” noted founding director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai Eric Schadt, Ph.D., who was not involved with the STSI research. “The Wellderly Study presents an attractive alternative by studying those who are well in order to uncover the solutions nature has provided to protect us against disease. The initial discoveries around protective factors for Alzheimer’s disease and coronary artery disease demonstrate the keys the Wellderly may hold in unlocking ways in which we all may live healthier lives.”

Source:

Pull-apart Chocolate Bread

Ingredients

1/3 cup granulated sugar
1/4 cup warm water
2 tsp active dry yeast
3/4 cup milk
1/4 cup butter, melted
2 eggs
2 tsp vanilla
1/4 tsp salt
4-1/2 cups all-purpose flour (approx)
1 cup mini chocolate chips

Chocolate Topping

3 tbsp butter, melted
1/2 cup granulated sugar
2 tbsp cocoa powder

Icing

1/2 cup icing sugar
1 tbsp water

Method

  1. In large bowl, dissolve 1 tsp of the sugar in warm water. Sprinkle in yeast; let stand for about 10 minutes or until frothy.
  2. Whisk in remaining sugar, milk, melted butter, eggs, vanilla and salt. Whisk in 2 cups of the flour. With wooden spoon, stir in enough of the remaining flour, 1/2 cup at a time, to make soft, slightly sticky dough.
  3. Turn out dough onto lightly floured surface; knead for about 10 minutes or until smooth and elastic, adding enough of the remaining flour as necessary. Knead in chocolate chips.
  4. Place in greased bowl, turning to grease all over. Cover with plastic wrap; let rise in warm draft-free place until doubled in bulk, about 1 hour.
  5. Grease 10-inch tube pan; set aside.
  6. Chocolate Topping: Punch down dough. Divide into 24 portions; shape each into ball. Place butter in small bowl. In separate bowl, combine sugar with cocoa powder. Roll balls first in melted butter, then in cocoa mixture. Arrange in prepared pan. Cover with plastic wrap; let rise in warm draft-free place until almost doubled in bulk, about 40 minutes.
  7. Preheat oven to 350ºF.
  8. Bake for 45 minutes or until golden. Let cool in pan on rack for 10 minutes. Remove bread from pan; let cool completely.
  9. Icing: Stir sugar with water until smooth; drizzle over bread. Makes 24 buns.

Makes 24 buns.

Source: Style At Home


Today’s Comic

Korean-style Stewed Pork Ribs

Ingredients

1-1/3 lb pork ribs, cut into 2-inch long pieces
2 tbsp oil
1/3 carrot
20 gingko nuts
2 potatoes
2 green peppers
pine nuts and sliced red dates for garnish

Seasoning

2-1/2 tbsp soy sauce
1-1/2 tbsp sugar
6 tbsp green onion
2 tbsp garlic
2 tbsp ginger juice
2 tbsp rice wine

Method

  1. Score the spareribs on both sides.
  2. Stir-fry the ginko nuts in a lightly salted pan until they turn green color. Then rub off the top-skins.
  3. Heat 2 tbsp oil in a pan, fry the spareribs until brown. Remove excess oil and place the ribs in a pot.
  4. Mix the seasoning ingredients in a bowl. Add half of the mixture and 2 cups water to the ribs and cook them on high heat for 10 minutes.
  5. When the ribs are tender, add the gingko nuts, the carrots and potatoes cut into flower shapes and the remaining seasoning. Toss to combine and cook for 2 more minutes.
  6. Remove the ribs and vegetables to a serving dish and garnish with the sliced red dates and pine nuts.

Source: Healthful Korean Cooking

Mysteries of ‘Good Cholesterol’

Every once in a while, a study comes along that leaves you wondering what you just read and what it really means. Researchers at the University of Cambridge published a new study in the journal Science seems to throw sand on the traditional medical wisdom that says high levels of good cholesterol are beneficial for our hearts. “Twenty years ago, if you had high bad cholesterol and high good cholesterol, doctors said don’t worry about it — one offsets the other,” Scott Wright, M.D., a cardiologist at Mayo Clinic, tells The Huffington Post in a story about the study. “I never really bought that … You can have a heart attack despite having a high level of good cholesterol.”

We asked Dr. Wright to help us sort through what the Cambridge study means. The study found that “some people with naturally high good cholesterol due to a genetic mutation” are actually at an elevated risk for heart disease.

First of all, Dr. Wright tells us, cholesterol is just one of a “large number of risk factors” that play into our chances of heart disease. Then he explained that “about two percent of the patients in that study had high levels of good cholesterol, but that wasn’t helping them, because they lacked a receptor to allow their good cholesterol to dump all of the fats inside of it out of their body.” For the rest of us, though, he says, there is some benefit. “For 98 percent of us, high or elevated levels of good cholesterol are relatively still a good thing. It’s helping reduce our risk a bit.”

The two percent of patients in the study who were not helped have what’s called a SCARB1 gene mutation, which affects “1 out of every 1,700 people.” Those how have it, though, are “at an 80 percent increased risk” for heart disease, according to Huffington Post.

We still needed a little help understanding.

“Here’s how cholesterol works,” Dr. Wright tells us. “Good cholesterol is like your garbage company, and bad cholesterol is like your FedEx and UPS driver – it delivers packages throughout your body. Good cholesterol takes the leftovers from those packages – the garbage, the recyclables, the bad stuff – and dumps it out of your body for you. But for the two percent of people who have this SCARB1 mutation, their garbage trucks don’t empty. And so their cholesterol levels just get higher and higher and they’re then stuck with all of those toxins circulating around in their blood. That’s why it’s so harmful for them.”

Whatever your metaphor of choice, Dr. Wright and The Huffington Post say the “classic nutrition advice” still holds true when it comes to reducing our risk for heart trouble. (Refuse delivery when you hear a knock on the door?) “We can always lower our risk of heart attacks and heart disease by not smoking, losing weight, exercising regularly, keeping our blood pressure normal, keeping our diabetes well managed, eating a low-fat diet, and doing whatever we can to keep our lives as low-stress as possible,” Dr. Wright says. “Those are the tried and true things that all of us can always do to reduce our risk.”

Source: Mayo Clinic

In Pictures: Roasted Beef Rice Bowls for Lunches

Problems Finding Your Way Around May be Earliest Sign of Alzheimer’s Disease

Long before Alzheimer’s disease can be diagnosed clinically, increasing difficulties building cognitive maps of new surroundings may herald the eventual clinical onset of the disorder, finds new research from Washington University in St. Louis.

“These findings suggest that navigational tasks designed to assess a cognitive mapping strategy could represent a powerful new tool for detecting the very earliest Alzheimer’s disease-related changes in cognition,” said senior author Denise Head, associate professor of psychological and brain sciences in Arts & Sciences.

“The spatial navigation task used in this study to assess cognitive map skills was more sensitive at detecting preclinical Alzheimer’s disease than the standard psychometric task of episodic memory,” she said.

Preclinical Alzheimer’s disease denotes the presence of Alzheimer-related changes in the brain that occur prior to the development of symptoms that lead to the diagnosis.

The cognitive findings from this study, published in the April issue of the Journal of Alzheimer’s Disease, are consistent with where in the brain the ill effects of Alzheimer’s disease first surface, as well as with the progression of the disease to other brain regions.

Previous research has shown that navigation problems crop up early in individuals with Alzheimer’s disease. These deficits may be associated with the build up of amyloid plaques and tau tangles and other signs of deterioration and shrinkage in the brain’s prefrontal cortex, hippocampus and caudate.

The hippocampus, which is associated with long-term memory storage, the recognition of new surroundings and the creation of cognitive maps, is well-established as an early target for Alzheimer’s-related damage. Similar damage also turns up in the caudate, which is associated with learning as well as voluntary movement.

“Our observations suggest a progression such that preclinical Alzheimer’s disease is characterized by hippocampal atrophy and associated cognitive mapping difficulties, particularly during the learning phase,” said first author Samantha Allison, a psychology doctoral student at Washington University. “As the disease progresses, cognitive mapping deficits worsen, the caudate becomes involved, and route learning deficits emerge.”

Making a mental map

While these deficits are well documented in patients with early stage Alzheimer’s disease, they have not been well studied in seemingly normal patients who may be progressing toward identifiable early stages of the disease, a status known as preclinical Alzheimer’s disease.

In this study, researchers used a virtual maze navigation experiment to examine whether specific problems with route learning and cognitive map building, which involve the caudate and the hippocampus, respectively, could be detected in preclinical Alzheimer’s. The experiment’s design plays on the fact that humans generally find their way in life using two distinct forms of spatial representation and navigation.

With egocentric navigation, people rely on past knowledge to follow well-worn routes, moving sequentially from one landmark to another until they reach their target destination. In allocentric navigation, people become familiar with their big picture surroundings and create a mental map of existing landmarks, allowing them to plot best available routes and find shortcuts to new destinations.

Participants in this study were separated into three groups based on a test of brain and spinal fluids that can detect biomarkers shown to predict the future development of Alzheimer’s-related plaques and tangles in the brain. People who are clinically normal with these markers are considered to have preclinical Alzheimer’s disease.

This study included 42 clinically normal individuals who lacked the cerebrospinal fluid markers for Alzheimer’s, 13 clinically normal individuals who were positive for these markers and thus had preclinical Alzheimer’s, and 16 individuals with documented behavioral symptoms of early stage Alzheimer’s.

All 71 study participants spent about two hours on a desktop computer being tested on their ability to navigate a virtual maze consisting of a series of interconnected hallways with four wallpaper patterns and 20 landmarks. Participants were tested on two navigation skills: how well they could learn and follow a pre-set route, and how well they could form and use a cognitive map of the environment. Participants were given 20 minutes to either learn a specified route, or to study and explore the maze with a navigation joystick. They were then tested on their ability to recreate the route or find their way to specific landmarks in the environment.

“People with cerebrospinal markers for preclinical Alzheimer’s disease demonstrated significant difficulties only when they had to form a cognitive map of the environment — an allocentric, place-learning navigation process associated with hippocampal function,” Head said. “This same preclinical Alzheimer’s disease group showed little or no impairment on route learning tasks — an egocentric navigation process more closely associated with caudate function.”

When compared with cognitively normal study participants who lacked the cerebrospinal fluid markers of Alzheimer’s, those with preclinical Alzheimer’s disease scored lower on their ability to learn the locations of objects in the environment in relation to each other during the initial study phase.

While these results suggest deficits in the ability to form a cognitive map, preclinical Alzheimer’s disease participants eventually managed to overcome these map-learning deficits, performing almost as well as cognitively normal participants during a subsequent wayfinding navigation task.

“These findings suggest that the wayfinding difficulties experienced by people with preclinical Alzheimer’s disease are in part related to trouble acquiring the environmental information,” Head said. “While they may require additional training to learn new environments, the good news here is that they seem to retain sufficient information to use a cognitive map almost as well as their cognitively normal counterparts.”

A more sensitive diagnostic?

Head cautions that the current study has several limitations, including a relatively small sample size and a lack of direct information about brain regions and networks that have a role in spatial navigation and wayfinding.

However, Allison notes, “We are currently investigating how brain regions impacted early during the course of the disease are related to cognitive mapping deficits in a larger sample of individuals with preclinical Alzheimer’s disease.”

Within the context of these limitations, the current investigation demonstrates significant preclinical Alzheimer’s disease-related deficits in aspects of cognitive mapping with relative preservation in route learning. In contrast, people experiencing memory lapses and other behavioral problems associated with early stage Alzheimer’s disease had clear difficulties both in learning an established route and in finding their own way to new landmarks.

“This pattern is consistent with decrements in hippocampal integrity prior to changes in the caudate,” Head said. “These findings suggest that navigational tasks designed to assess a cognitive mapping strategy could represent a powerful tool for detecting the very earliest Alzheimer’s disease-related changes in cognition.”

Participants in the study came from an ongoing study at Washington University’s Charles F. and Joanne Knight Alzheimer’s Disease Research Center. Scientists have been following participants with and without a family history of the disease, with the aim of identifying Alzheimer’s disease biomarkers most closely associated with the development of full-blown disease years later.

The research team notes that the presence of cerebrospinal fluid markers for preclinical Alzheimer’s does not guarantee that a person will go on to develop full blown Alzheimer’s. “Future research should examine whether cognitive mapping deficits in individuals in preclinical Alzheimer’s are associated with an increased risk of developing symptomatic Alzheimer’s,” they said.

Other study co-authors, both from Washington University School of Medicine, include Anne M. Fagan, professor of neurology, and John C. Morris, MD, director of the Charles F. and Joanne Knight Alzheimer’s Disease Research Center and the Harvey A. and Dorismae Hacker Friedman Distinguished Professor of Neurology.

Source: EurekAlert!


Today’s Comic

Chinese Stir-fry of Chicken and Asparagus

Ingredients

1/2 lb asparagus, cut off ends and cut into sections
1/2 lb chicken breast, cut into thick shreds
3 oz carrot, cut into strips
1 clove garlic, minced

Marinade

1/8 tsp salt
1/2 tsp cornstarch
1/2 tsp wine
dash of ground white pepper

Seasoning

1/4 tsp salt
1/4 tsp sugar,
dash of ground white pepper
1/2 cup chicken broth

Sauce

1 tsp light soy sauce
1/2 tsp sugar
dash of ground white pepper
1/8 tsp sesame oil,
4 tsp cornstarch
2 tbsp chicken broth

Method

  1. Mix marinade ingredients in a bowl. Add marinade to chicken. Mix well and set aside for 10 minutes.
  2. Add seasoning ingredients to a wok. Bring to a boil. Add carrot and asparagus and cook for a while. Remove.
  3. Blanch chicken in hot oil until cooked. Remove and drain off oil.
  4. Saute garlic with 1 tbsp oil in the wok. Drizzle 1 tsp Chinese cooking wine. Return carrot, asparagus and chicken to wok. Add sauce ingredients and stir-fry. Remove to serving platter when the sauce thickens.

Source: Chinese Home Cooking