Half of Alzheimer’s cases misdiagnosed

This blog post by Dr. Sanjay Gupta (of CNN) is about the low diagnostic accuracy rate of Alzheimer’s Disease. Over 400 brain autopsies were done on Japanese-American men. “Only about half of those who had a diagnosis of Alzheimer’s before death had the brain plaques that signal the disease. The dementia in the other half appeared to have been caused by abnormal protein deposits (known as Lewy bodies), stroke-related tissue death (microinfarcts), cell damage, or some combination thereof.”

Why is an accurate diagnosis important? “Ruling out other forms of dementia may help relatives plan for future care and determine their own risk for Alzheimer’s, for instance. Accurately diagnosing Alzheimer’s is even more critical for research on potential treatments.”

As many of you know, I’m a proponent of brain donation. If anyone wants help making these arrangements, I’m happy to volunteer my time to do this. It can never be too early to make these arrangements. A gentleman with a clinical diagnosis of Dementia with Lewy Bodies died this week. His wife and I made the brain donation arrangements nearly two years ago! She was very thankful that she didn’t have to stress over these arrangements when her husband’s death became imminent or after he died. All went according to plan.

I’ve copied the short blog post below and a link to it. This news article was posted today to an LBD-related online support group.

http://pagingdrgupta.blogs.cnn.com/2011 … diagnosed/

Paging Dr. Gupta: Blog by Dr. Sanjay Gupta
CNN Health
February 23rd, 2011

Half of Alzheimer’s cases misdiagnosed

Roughly half of the people who are told they have Alzheimer’s disease may in fact have other forms of dementia that produce similar symptoms, according to a new study.

Doctors have known for some time that the confusion and memory loss caused by the brain lesions associated with Alzheimer’s can also be caused by other types of brain changes, such as tissue damage stemming from strokes. The study suggests that it may be even harder than previously thought to identify the source of dementia while a patient is still alive, says lead researcher Lon White, M.D.

“There are at least five different kinds of important lesions which can produce a picture that looks like Alzheimer’s,” says White, a professor of geriatric medicine at the University of Hawaii in Honolulu. “Each of those five kinds of lesions is apparently driven by its own pathologic process, and having one doesn’t protect you from having others. All are independent and all are increasing with age.”

White and his colleagues performed brain autopsies—the only surefire way of diagnosing Alzheimer’s—on more than 400 elderly Japanese-American men. Only about half of those who had a diagnosis of Alzheimer’s before death had the brain plaques that signal the disease. The dementia in the other half appeared to have been caused by abnormal protein deposits (known as Lewy bodies), stroke-related tissue death (microinfarcts), cell damage, or some combination thereof.

The researchers have since completed another 400 or so autopsies with similar results, and will present their findings in April at the annual meeting of the American Academy of Neurology. Unlike studies published in medical journals, these findings are still preliminary and have yet to be thoroughly vetted by other experts in the field.

An Alzheimer’s misdiagnosis doesn’t have immediate consequences for the patient because no treatments exist that can stop the steady progression of the disease. And the drugs that, in some people, help slow Alzheimer’s or make it more tolerable appear to work for other types of dementia, White says.

Patients and their families can nevertheless benefit from an early and accurate diagnosis. Ruling out other forms of dementia may help relatives plan for future care and determine their own risk for Alzheimer’s, for instance.

Accurately diagnosing Alzheimer’s is even more critical for research on potential treatments. Without knowing precisely who has Alzheimer’s, pharmaceutical companies that have been developing new drugs “are not going to be able to see a true assessment of how effective their drug is,” White says.

Some promising advances in diagnosis have been made recently. A study published last year found that spinal fluid tests can predict Alzheimer’s with a high degree of accuracy, and the Food and Drug Administration is currently weighing the approval of a brain scan that uses dye to highlight the plaques characteristic of Alzheimer’s. The reliability of these methods needs to be confirmed, however.

“Everybody knows we need to do a better job of diagnosing,” says Maria Carrillo, Ph.D., the senior director of medical and scientific relations at the Alzheimer’s Association, a research and advocacy organization based in Chicago. “We are all trying to make that diagnosis better, earlier, faster. All of those things are currently under way in terms of research study.”

How disordered proteins spread

This news article, written for laypeople, is about how disordered proteins spread from neuron to neuron in Huntington’s Disease, and probably in other diseases as well (such as PD, AD, PSP, and CBD). What seems to be new here is a confirmation that the misfolded protein spends part of its time outside neurons as this “opens up the possibility for therapeutics.”

http://news.stanford.edu/news/2011/febr … 21811.html

Stanford Report
February 18, 2011
Stanford researchers study how disordered proteins spread from cell to cell, potentially spreading neurodegenerative disease

Misfolded proteins can get into cells and form large aggregates by recruiting normal proteins. These aggregates are associated with neurodegenerative diseases. Stanford biology Professor Ron Kopito has found that the protein linked to Huntington’s can spread from one cell to another. His research may explain how these diseases spread through our brains, an understanding that might lead to the development of drugs to target the misfolded proteins.

By Sandeep Ravindran

One bad apple is all it takes to spoil the barrel. And one misfolded protein may be all that’s necessary to corrupt other proteins, forming large aggregations linked to several incurable neurodegenerative diseases such as Huntington’s, Parkinson’s and Alzheimer’s.

Stanford biology Professor Ron Kopito has shown that the mutant, misfolded protein responsible for Huntington’s disease can move from cell to cell, recruiting normal proteins and forming aggregations in each cell it visits.

Knowing that this protein spends part of its time outside cells “opens up the possibility for therapeutics,” he said. Kopito studies how such misfolded proteins get across a cell’s membrane and into its cytoplasm, where they can interact with normal proteins. He is also investigating how these proteins move between neuronal cells.

The ability of these proteins to move from one cell to another could explain the way Huntington’s disease spreads through the brain after starting in a specific region. Similar mechanisms may be involved in the progress of Parkinson’s and Alzheimer’s through the brain.

Kopito discussed his research Friday at the annual meeting of the American Association for the Advancement of Science in Washington, D.C.

Not all bad

Not all misfolded proteins are bad. The dogma used to be that all our proteins formed neat, well-folded structures, packed together in complexes with a large number of other proteins, Kopito said. But over the past 20 years, researchers have found that as much as 30 percent of our proteins never fold into stable structures. And even ordered proteins appear to have some disordered parts.

Disordered proteins are important for normal cellular functions. Unlike regular proteins, they interact with only one partner at a time. But they are much more dynamic, capable of several quick interactions with many different proteins. This makes them ideal for a lot of the standard communication that happens within a cell for its normal functioning, Kopito said.

But if some of our proteins are always disordered, how do our cells tell which proteins need to be properly folded, and which don’t? “It’s a big mystery,” said Kopito, and one that he’s studying. This question has implications for how people develop neurodegenerative diseases, all of which appear to be age-related.

Huntington’s disease is caused by a specific mutated protein. But the body makes this mutant protein all a person’s life, so why does that person get the disease in later adulthood? Kopito said it’s because the body’s protective mechanisms stop doing their job as we get older. He said his lab hopes to determine what these mechanisms are.

A bad influence

But it’s clear what happens when these mechanisms stop working – misfolded proteins start recruiting normal versions of the same protein and form large aggregations. The presence of these aggregations in neurons has been closely linked with several neurodegenerative diseases.

Kopito found that the mutant protein associated with Huntington’s disease can leave one cell and enter another one, stirring up trouble in each new cell as it progresses down the line. The spread of the misfolded protein may explain how Huntington’s progresses through the brain.

This disease, like Parkinson’s and Alzheimer’s, starts in one area of the brain and spreads to the rest of it. This is also similar to the spread of prions, the self-replicating proteins implicated in mad cow disease and, in humans, Creutzfeldt-Jakob disease. As the misfolded protein reaches more parts of the brain, it could be responsible for the progressive worsening of these diseases.

Now that we know that these misfolded proteins spend part of their time outside of cells, traveling from one cell to another, new drugs could target them there, Kopito said. This could help prevent or at least block the progression of these diseases.

Kopito is currently working to figure out how misfolded proteins get past cell membranes into cells in the first place. It is only once in the cell’s cytoplasm that these proteins can recruit others. So these studies could help find ways to keep these mischief-makers away from the normal proteins.

He is also collaborating with biology Professor Liqun Luo to track these proteins between cells in the well-mapped fruit fly nervous system. In the future, Kopito said he hopes to link his cell biology work to disease pathology in order to understand the role misfolded proteins play in human disease.

Sandeep Ravindran is a science-writing intern at the Stanford News Service.

Tau Induced Memory Loss in Alzheimer’s is Reversible

The Alzheimer’s Reading Room has a nice summary of German research published last week that appears to show “that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off” in mice with a human tau gene. This suggests that the progression of Alzheimer’s Disease may be reversible. Here’s the summary:

http://www.alzheimersreadingroom.com/20 … imers.html

The really important discovery here, however, is that the progression of Alzheimer’s disease can be reversed in principle – at least at an early stage of the illness before too many neurons have been destroyed…

Tau Induced Memory Loss in Alzheimer’s is Reversible
Friday, February 18, 2011
Alzheimer’s Reading Room

Amyloid-beta and tau protein deposits in the brain are characteristic features of Alzheimer disease. The effect on the hippocampus, the area of the brain that plays a central role in learning and memory, is particularly severe. However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off.

Researchers from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part.

The scientists are now testing active substances to prevent the formation of tau deposits in mice. This may help to reverse memory loss in the early stages of Alzheimer disease – in part, at least. Journal of Neuroscience, February 16, 2011.

Whereas aggregated amyloid-beta protein forms insoluble clumps between the neurons, the tau protein accumulates inside them. Tau protein stabilises the tube-shaped fibers of the cytoskeleton, known as microtubules, which provide the “rails” for cellular transport.

In Alzheimer disease, excess phosphate groups cause the tau protein to malfunction and form clumps (the ‘neurofibrillary tangles’). As a result, nutrient transport breaks down and the neurons and their synapses die off. This process is accompanied by the initial stage of memory loss.

Together with colleagues from Leuven, Hamburg and Erlangen, Eva and Eckhard Mandelkow’s team from the Max Planck Research Unit for Structural Molecular Biology generated regulatable transgenic mice with two different human tau gene variants that can be switched on and off again: one group was given a form of the protein that cannot become entangled (anti-aggregant), and a second was provided with the code for the strongly aggregating protein variant (pro-aggregant). The mice with the first form developed no Alzheimer symptoms; the rodents that were given the pro-aggregant tau developed the disease.

The scientists measured the mice’s memory loss with the help of a swimming test: the healthy mice quickly learn how to find a life-saving platform located under the surface of the water in a water basin.

In contrast, the transgenic animals, which have the additional pro-aggregant tau gene paddle aimlessly around the basin until they accidentally stumble on the platform; they require over four times more time to do this than their healthy counterparts.

However, if the mutated toxic tau gene is switched off again, the mice learn to reach “dry land” with ease just a few weeks later. As a control, the mice with the anti-aggregant form of tau have no defects in learning, just as normal non-transgenic mice.

Surprising tissue results

Tissue tests showed that, as expected, no tau clumps had formed in the brains of the first group of mice expressing anti-aggregant tau.

In the second group – the mice suffering from Alzheimer’s – co-aggregates from human tau and “mouse tau” were formed – against expectations, because tau protein from mice does not usually aggregate.

“Even more astonishingly, weeks after the additional gene had been switched off, the aggregated human tau had dissolved again. However, the ‘mouse tau’ remained clumped. Despite this, the mice were able to learn and remember again,” says Eckhard Mandelkow. More precise tests revealed that new synapses had actually formed in their brains.

The scientists concluded from this that mutated or pathological tau can alter healthy tau. It appears that pro-aggregant tau can act similar to a crystal nucleus – once it has started to clump up, it drags neighboring “healthy” tau into the clumps as well. This is what makes the process so toxic to the neurons.

“The really important discovery here, however, is that the progression of Alzheimer’s disease can be reversed in principle – at least at an early stage of the illness before too many neurons have been destroyed,” explains Eva Mandelkow who, together with her husband, will be awarded the Potamkin Prize 2011 for Alzheimer’s disease research, which is sponsored by the American Academy of Neurology.

The aggregation of tau proteins, however, cannot simply be switched off in humans the way it can in the transgenic mice. Nevertheless, special substances exist that could dissolve the tau aggregates. By screening 200,000 substances, the Hamburg researchers have already identified several classes of active substances that could re-convert the tau aggregates into soluble tau. These are now being tested on animals.
___________________________________
Original work:
Tau-induced Defects in Synaptic Plasticity, Learning and Memory are reversible in Transgenic Mice after Switching off the Toxic Tau Mutant
Astrid Sydow, Ann Van der Jeugd, Fang Zheng, Tariq Ahmed, Detlef Balschun, Olga Petrova, Dagmar Drexler, Lepu Zhou, Gabriele Rune, Eckhard Mandelkow, Rudi D’Hooge, Christian Alzheimer, Eva-Maria Mandelkow
Journal of Neuroscience, February 16, 2011

“Dealing with Drooling” (Neurology Now article)

There’s a good article in the latest issue of Neurology Now magazine on the treatment of drooling in neurological disorders. Dr. Robert Miller (a neurologist at Stanford and at the ALS center at CPMC San Francisco) is quoted in the article as saying: “We tend to think that since some of these [neurologic] conditions are incurable, they’re also untreatable. That’s a big mistake. We have many treatments—for the breathing issues, the nutritional issues, treatments that slow the progression of disease, and yes, treatments for drooling.”

The article mentions the medication glycopyrrolate (brand name=Robinul). Generally speaking, caution should be exercised when giving an anticholinergic medication such as Robinul to someone to dementia (as there may already be a lack of acetylcholine in the brain of someone with dementia).

Neurology Now is a magazine written for laypeople. Subscriptions to the bimonthly publication are available at no charge; see:
http://journals.lww.com/neurologynow/Pa … vices.aspx

Robin

http://journals.lww.com/neurologynow/Fu … id.15.aspx

EYE ON THERAPY
Dealing with Drooling
Getting rid of excess saliva goes high-tech.
by Amy Paturel, MS, MPH

Neurology Now
February/March 2011; Volume 7(1); Pp 38,40

When 61-year-old Deborah Clark first experienced trouble swallowing, she didn’t think much of it. But six months later, when she began having symptoms like slurred speech and difficulty projecting her voice, she visited a neurologist. Diagnosed with amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s disease) in February 2008, Clark quickly discovered how integral the muscles in her mouth were to her quality of life. Not only did she have difficulty speaking, but she also experienced excess saliva pooling in her mouth. At its worst, Clark found herself changing clothes up to four times a day because she had drooled down the front of her shirt.

“I was reluctant to be in public or around strangers—especially when a meal was involved,” says Clark. “People were always offering me tissues to control the drooling. It was embarrassing.”

Drooling, or sialorrhea, can be a major problem for people with neurologic conditions ranging from Parkinson’s disease and cerebral palsy to certain types of stroke and ALS. People with these conditions may not have the brain control to coordinate muscle movements in the face and mouth.

“Any condition that affects the muscles and nerves of the bulbar area (the swallowing mechanism) could cause increased drooling,” says Steven Bachrach, M.D., co-director of the Cerebral Palsy Program for Alfred I. duPont Hospital for Children in Wilmington, DE. And if you’re not swallowing your saliva, it tends to pool and accumulate in the mouth, and then it starts overflowing.

Beyond the obvious social implications of incessant drooling, the overflow of saliva in the mouth can irritate tissues around the lips and even cause aspiration pneumonia, a serious condition where people breathe fluid (or other foreign materials) from the mouth into the lungs. But with recent advances in everything from oral medication to botulinum toxin injections, people have more options than ever to control sialorrhea.

SWALLOWING THERAPY
Speech and swallowing therapy is a great option for people who are mildly impaired and highly motivated to control their drooling. Most neurologists will advise patients to investigate this approach before considering invasive procedures. Through a series of sessions, therapists teach patients a variety of techniques to improve the safety of swallowing and minimize the risks of aspiration.

“There’s a lot that a swallowing therapist can do in this area,” says Robert Miller, M.D., professor of neurology at Stanford University and director of the Forbes Norris ALS Research Center at the California Pacific Medical Center in San Francisco. “If you tuck in your chin when you’re swallowing, for example, you’ll open up the airway, making it easier for fluid and food to go down.”

Even just becoming more aware of when and how you swallow can be effective. With regular training, people can learn to swallow more efficiently and get rid of excess saliva. Unfortunately, none of these techniques actually dries up the spit. If that’s your goal, medications or surgery are your best bets.

MEDICATION
When less invasive methods have failed, the next approach is medication, usually anti-cholinergic medications. This class of drugs is used for everything from seasickness to overactive bladder. But with dry mouth as one of the main side effects, anti-cholinergics have become a useful tool to control drooling. In fact, studies investigating glycopyrrolate (the most commonly prescribed medication for drooling) consistently find the drug reduces drooling for up to 95 percent of patients who try it.

“One of the biggest challenges was that glycopyrrolate was only available in tablet form, so it was hard to adjust the dose to very small amounts,” says Dr. Bachrach. But in January 2011, the Food and Drug Administration approved a liquid form of the drug, which will make it easier to take and easier to dose.

When Clark started taking glycopyrrolate, her drooling improved within a matter of days. Initially she took one tablet three times a day, but eventually she needed four tablets daily to experience the same effects. Over time, even four tablets didn’t reduce her drooling to an acceptable level.

“Even if the drugs do work initially, receptors on the cells and within the salivary glands change, so patients may end up requiring higher and higher doses to get the same result—and then they get side effects,” says Scott Brietzke, M.D., M.P.H., director of pediatric otolaryngology at the Walter Reed Army Medical Center in Washington D.C. While dry mouth is the most common side effect, some people also experience constipation, urinary retention, and cognitive side effects such as confusion and memory impairment.

If the anti-cholinergics stop working—or the side effects are intolerable—some physicians prescribe amitriptyline, an anti-depressant that dries up saliva. A bonus: amitriptyline improves sleep, which is often disrupted in patients with ALS, multiple sclerosis, and other neurologic disorders.

INJECTIONS
If meds can’t control drooling, botulinum toxin is another option. Using an ultrasound-guided approach, the physician injects the drug into the major salivary glands to paralyze the muscles that normally squeeze out saliva. In one study of 131 patients, published in the medical journal Archives of Otolaryngology Head and Neck Surgery in 2010, botulinum toxin injections in the submandibular glands (the two glands located in the lower jaw that produce most of the saliva) reduced drooling and improved quality of life among patients who received injections. Two months after the injections, nearly 50 percent of patients experienced significant improvement, with effects beginning to taper off at the eight-month mark.

Clark started with just two shots into the salivary glands on either side of her face. Within a week, her drooling had dissipated more than it had with glycopyrrolate alone, and the effects lasted for three months. On the heels of this success, Clark’s physician gradually increased her dose to a total of six shots (three on each side).

“With six shots, the results were much more dramatic,” says Clark. “I have very little drooling and the only side effect is dry mouth, which is easier to deal with than drooling.” After the last round of botulinum toxin, Clark discontinued the glycopyrrolate without any noticeable difference.

Studies suggest that combined injections in both the parotid glands (which are located in the cheeks) and submandibular glands are slightly more effective than injections into the submandibular glands alone. And after repeated injections, there have been some reports that the salivary glands actually stop working, resulting in a permanent reduction in drooling. “You can’t count on that,” says Dr. Bachrach, “but it does happen in some patients.”

For other people, though, botulinum toxin is just a trial procedure to determine whether surgery will be effective. “Botulinum toxin deactivates those major glands, so we can see if that helps the patient with either the social problem or aspiration,” says Dr. Brietzke. “If there’s significant improvement, then we can consider a potentially irreversible procedure, such as tying off the ducts or removing the glands.”

SURGERY
Surgical treatment for drooling may be even more effective than injections, without subjecting people to recurrent treatments. Studies show that people who have surgery are generally happy with the results. Unfortunately, there are a variety of approaches and little consensus about which ones work best. The most straightforward procedure involves the submandibular glands: Rerouting the ducts from these glands to the back of the mouth makes it easier to swallow saliva. Alternatively, surgeons can reroute the ducts from the parotid glands or remove the submandibular glands altogether.

“The evidence we have suggests that intra-oral procedures (like tying off the four ducts in the mouth) may not be as successful,” says Dr. Brietzke. According to a study he co-authored in Archives of Otolaryngology Head and Neck Surgery in 2009, removal of the submandibular glands and parotid duct rerouting appear to have the highest success rates at 87.8 percent while the success rates for tying off the four ducts varied wildly from 31 to 100 percent.

“The biggest downside is that surgery is not reversible,” says Dr. Bachrach. “Once you’ve tied off the ducts, or removed the glands altogether, you can’t undo that.” So while you can go from drooling to dry, you can’t go back. And dry mouth has its own set of complications.

Even so, treating symptoms like drooling still gets short shrift from some health care providers.

“We tend to think that since some of these [neurologic] conditions are incurable, they’re also untreatable,” says Dr. Miller. “That’s a big mistake. We have many treatments—for the breathing issues, the nutritional issues, treatments that slow the progression of disease, and yes, treatments for drooling.”

For Clark, that treatment has been invaluable. Today, she no longer carries a napkin with her at all times, she doesn’t shy away from social events, even with strangers, and her shirt stays dry throughout the day. “I’m very happy with the results,” she says.

Story in O Magazine about woman with Lewy body dementia

LBD folks –

Apparently the March 2011 issue of O Magazine (O for Oprah) has an article titled “Before I Forget” by Beth Macy about a woman with Lewy Body Dementia.  I haven’t seen the article yet; it’s wonderful that LBD is getting some attention in the popular press.  But I am aware of Beth Macy’s writings in her blog “Intrepid Paper Girl” about this woman, Lynn Forbish.  Beth beautiful writes on the topic of caregiving on rare occasions.

Beth Macy is a writer at the Roanoke Times newspaper.  At a party Beth went to several years ago, a recently retired copy editor from the same newspaper came up to her and said “I have dementia — in case you didn’t know!”  Beth didn’t know.  The retired copy editor, Lynn Forbish, had been diagnosed at 63 with Lewy Body Dementia.  “Sometimes I can’t remember whether to hook my bra in the front or the back,” Lynn told Beth.  Beth writes that “in losing her memory, [Lynn] had regained part of herself.”

I’ve copied below the story Beth wrote in 2007 about Lynn for the Roanoke Times.  Lynn was mad that former co-workers didn’t visit her any more.  Lynn joked that she’d like to send them a Christmas card that read:  “I have dementia, not f—-g herpes!”

Robin

http://www.roanoke.com/health/wb/wb/xp-115806

Dementia causes one to lose her edge
Once, Lynn Forbish was sharp, witty, mercilessly precise. Now a fast-moving form of dementia has changed her life, and in some unexpected ways.
By Beth Macy
The Roanoke Times
Sunday, May 06, 2007

For someone whose livelihood depended on her mastery of language, it troubled Lynn Forbish when she’d struggle to extract an everyday word from memory — “cafeteria,” say — only to have “mess hall” pop out instead.

Later, as the fuzzy thinking worsened, it was her bra that gave her fits: Did the damn thing hook in the front or the back? Just whose idea was it for women to wear these things anyway?

A year ago when she was diagnosed with Lewy body dementia, Lynn could still articulate what it felt like to lose her mind. In the straight-up way of a veteran journalist who knows better than to pussyfoot around the truth, she’d look you in the eye and say:

“I retired because I have dementia … in case you didn’t know!”

She would still correct you if you used “farther” instead of “further” — a holdover from the decades she spent manning newspaper copy desks.

She could still describe the scores of celebrities she’d interviewed in her prime, down to the details on Liberace’s rings.

Those abilities are gone now. In many ways, so is the old Lynn.

She’s been replaced by a softer version of herself — one who no longer teaches her grandchildren four-letter words. One who relies on her son and daughter-in-law to handle her finances, take her to the doctor and cut the meat on her dinner plate.

At 64, the new Lynn has found something the old Lynn never dreamed possible: In losing her memory, she’s found a part of herself.

‘I hate people’

“I work the Sunday New York Times crossword puzzle in ink,” she had boasted in her 1993 letter of application for the chief copy editor job at The Roanoke Times. “I play Scott Joplin rags and Chopin waltzes on an old upright piano that belonged to my great-grandmother.”

Her resume listed decades of experience as a reporter, editor and page designer, including at papers much larger than The Roanoke Times. But the newspaper’s editors had no idea how tough she’d had to be to pull it all off.

She was a single mother in the mid-’60s; her husband left when her son and daughter were 2 years and 6 months old, respectively. Later, he had their marriage annulled so he could remarry in the Catholic Church.

It was an experience Lynn never really got over, friends and family members say.

Her parents helped. But Larry Forbish recalls his mom’s supplementing her newspaper wages — at a department store and a drugstore, working three jobs at once — to pay for his braces. He remembers her hauling pails of cloth diapers to the Laundromat after long shifts at work.

At her hometown paper in Janesville, Wis., Lynn worked her way up from clerk-typist to reporter, covering police and school beats and writing features, too. She wrote essays, including a series about her own efforts to quit smoking: “I used to smoke three packs a day. Now I chew three packs a day.

“Gum, that is. I hate Doublemint gum. I hate people.”

On weekends, she reviewed entertainers who performed at nearby nightclubs, and later covered similar acts for the St. Petersburg (Fla.) Times, reviewing the likes of Milton Berle, Sammy Davis Jr. and Neil Diamond.

She leveled with Berle in print that he needed to get a new shtick. Of Diamond, she wrote that he would ruin his voice if he didn’t quit singing in that annoying gravelly style.

“She had a reputation for being a nutty madcap when she was here,” recalled Jeanette DeGroot, who worked alongside her in St. Petersburg in the ’70s and ’80s.

But as a night-shift copy editor, Lynn was fierce, priding herself on precision, skepticism and correcting others’ mistakes.

DeGroot recalls her once complaining that someone had tried to break into her apartment, although nothing was damaged or stolen.

How, then, did she know?

One of the plants on her balcony was moved two inches from where she’d put it. “Now that is a classic copy editor for you,” DeGroot said.

Crackerjack editor

About the same time her own mother was diagnosed with vascular dementia, Lynn moved to Roanoke to be near her son, Larry, and his wife, Katie; they were expecting a child.

Concerned about her own family health history, she ate antioxidant-rich foods long before they were the preventive rage. She played bridge, sold antique perfume bottles as a side business and balanced her checkbook in her head.

In journalism circles, the copy desk is known as the “Mount Everest of newsroom discontent,” and in Roanoke, Lynn was ruler of the summit. When she started working at The Roanoke Times in 1993, the paper was lucky to get her, and she didn’t hesitate to let everyone who worked with her know it.

Former business reporter Lois Caliri called her “a real crackerjack. She ran that place at night.”

Longtime reporter Laurence Hammack added: “She saved my butt many a time.”

Former copy editor Mike Kennedy said it was her “command presence” that allowed her to pull off coordinating phones, photographers and reporters when big news broke at night or on weekends.

“We’d sit back-to-back and gripe about things, and they used to call us ‘The Optimism Corner’ because we were so not the optimism corner,” Kennedy said.

Young editorial assistants were warned to tiptoe around her: Don’t turn your desk lamp on; it bothers her eyes. Don’t sit in her chair, or you’ll be ordered to vacate, pronto.

“When new people [editorial assistants] started, we actually had to teach them how to work when Lynn was working,” said Ellen Moseley, a copy editor and page designer. “But that was OK because she … deserved that kind of respect. She was the queen.”

Early in 2005, a computer-system switch was announced, a changeover Lynn dreaded and said so repeatedly. What she didn’t say — and what she’d managed to hide for several months — was her escalating forgetfulness.

Fears unmasked

During a spring trip to Florida, Lynn finally broke down, explaining tearfully to one of her oldest friends that she was having trouble remembering words, finding her car keys and keeping her once-meticulous house neat.

Back in Virginia, she kept her fears to herself. When her visual and spatial abilities began to waver at work — she repeatedly pressed the wrong button to receive a transferred call, for instance — she blamed the phone system.

Once when Moseley summoned the elevator to leave work for the night, she found Lynn inside — trapped, confused and, as she was wont to do in awkward situations: laughing. She hadn’t known which button to push.

Co-workers tried to help her adjust to the new computer system, writing her passwords down, making lists. They even called Larry to express concern.

He didn’t notice his mother faltering until Thanksgiving Day, when Lynn made her usual drive to his Bonsack home — and knocked on the next-door neighbor’s house. At her request, he crunched the numbers on her retirement accounts. She was relieved when he told her she could afford to retire two years early at 63.

“Something’s wrong with my brain,” she finally confided to Nancy Caldwell, a co-worker, just before she voluntarily retired in December 2005.

A few weeks earlier, she had momentarily forgotten what kind of work Caldwell did at the newspaper — when it was Lynn who had trained her in the first place.

Within a month of retiring, Lynn ran into a parked car and lost her driving privileges. When Larry picked her up from the police station, she still couldn’t comprehend what had happened.

“A stop sign just jumped out at me,” she said.

The only thing left to lose was her house.

A new vulnerability

Her home in the Virginia Heights area of Southwest Roanoke was a mess: Papers were stacked everywhere, including on the furniture and stairs. Daughter-in-law Katie Forbish discovered some of the medications Lynn was supposed to be taking mixed in with the cat food.

Her longtime neighbor Lisa Wade noticed lights on at odd hours. When she invited her to dinner, Lynn ate only a piece of bread, saying that food tasted metallic. She had lost 40 pounds.

“Lynn, honey, if you don’t start eating, you’re going to die,” Wade told her.

In February 2006, doctors at the Carilion Center for Healthy Aging diagnosed her with Lewy body dementia, which is rarer than Alzheimer’s disease — and progresses twice as fast. Patients last an average of five to seven years.

Larry was shocked. He knew she was having problems, but had chalked it up to retirement-related depression. “I felt guilty that I didn’t see earlier how bad she was getting. But the doctors shot the hell out of my denial.”

Such a reaction is not uncommon among children of dementia patients, according to Lynn’s geriatrician, Dr. Michael Berry. “When you start out being such a bright person, you have to come down a lot farther on the scales before it becomes obvious” to family members.

His mother, Berry explained, was now reading at a fifth-grade level, and her spatial and manipulative skills — the ability to work a puzzle or draw a simple diagram — scored in the mental retardation range. Protein lumps, called Lewy bodies, were in the nerve cells of her brain, causing it to shrink and impairing her ability to form new memories.

It was no longer safe for her to live at home alone. She needed to socialize and live among people. And she should make a record of her life soon — while she could still remember it.

Lynn had never been especially close to her daughter-in-law, but Katie Forbish put their history aside as she dug into researching Lynn’s disease — and finding her a new home. She interviewed directors of some 20 assisted-living facilities before choosing Ridgewood Gardens, now called Summerville.

“Her tongue was always her enemy,” Katie said. “But God has done a lot of healing with all of us.”

For the first time in decades, Larry added, she’s at peace.

When Lynn can’t think of a word, she no longer snaps at people for “patronizing” her by trying to finish her sentence.

Instead she laughs, a lot and often. In her lucid moments, she even jokes about her condition: “I kind of like this,” she said recently, when a friend arrived with a treat.

“Hey, maybe I’m just making all this dementia stuff up so I can be waited on!”

Though she hadn’t been to church regularly since childhood, Lynn began attending Baptist services with her family and asked Katie to buy her a large-print Bible. She started giving money to a myriad of charities — not just the ones targeted toward diseases that she might get.

“I think probably she is a very tender, loving person who just couldn’t let her hurts go,” Katie says.

“But now the hurts are being let go for her.”

Sometimes hints of the “old” Lynn still resurface: Last year, she threatened to send her former co-workers a Christmas card chastising them for not visiting her more. She joked that the card would read:

“I have dementia, not [expletive] herpes!”

Love interest

The woman who used to coordinate coverage of shootings and plane crashes can no longer dial a phone. She can’t put her sweater on by herself.

She has help, though, at Summerville, thanks to attendants and to her boyfriend, Don Memmer, a retired lawyer who lives down the hall and has a different, milder form of dementia. “He still drives!” Lynn brags. “And he has a car!”

Neither of them can operate the CD player or the VCR anymore, and Lynn looks despondently at her massive movie collection, trying to recall her favorite actor’s name. “It was the guy who played Columbo. … No, it was, it, it, it … Oh, dammit.”

It was Peter Sellers. It comes to her later, in the middle of another conversation.

Lynn and Don watch television mostly, and sometimes venture out in his car — although a recent trip to attend the Cat Fanciers Association Cat Show near Valley View turned into a joy ride instead. They drove around for three hours and never found the show.

Parkinson’s-like tremors have begun to settle into Lynn’s hands, apropos of Lewy body, and occasionally Lynn sees people who are not there. Nothing scary, usually: A pair of girls are lost and in her room, and Lynn calls Katie, asking her to help them find their way.

Moments of lucidity are increasingly rare but spot-on and classic Lynn: “Nobody’s gonna give you a medal or anything for being depressed, so you might as well laugh,” she said recently.

And: “I have no idea what happens to me when I go. But, see, now I don’t worry about that so much, so I guess it’s a blessing.”

Katie and Larry have read the statistics on caregivers — the soaring depression and high rates of divorce. “Sunday is Nana day,” Katie said, the day they take Lynn to church, then eat out. At Olive Garden, her favorite restaurant, they cut her food and help her when she tries to eat her fettuccine with a knife.

If it’s a nice day, sometimes Larry drives her to Rocky Mount where she tries to go over her inventory of antique perfume bottles and art-deco prints in the antique-mall booth Larry helps her maintain.

Katie talks to her on the phone for an hour every night. “It can consume your life if you let it,” Katie said. “When Katelyn was little, we’d get a baby sitter and then go out to dinner and talk about nothing but Katelyn. Now, we talk about Nana.”

Lynn can still be exasperating. When she misplaces an item, she insists that her housekeeper must have thrown it away. Not long ago, she accused Katie of stealing her favorite sweater.

No, Katie corrected, and located it for her.

Later that afternoon, Lynn apologized for the slight:

“I’m sorry I was such a poop-head today,” she said.