“Alzheimer’s vaccine stopped plaque, not dementia”

Interesting news today out of London about an AD vaccine that removed beta-amyloid protein in the brain of 7 patients but did nothing for their dementia.

http://www.salon.com/wires/ap/scitech/2 … index.html

Alzheimer’s vaccine stopped plaque, not dementia
By MARIA CHENG
Associated Press Writer

Jul 17th, 2008 | LONDON — Some doctors have long suspected that if the plaque that builds up in the brains of patients with Alzheimer’s disease could be removed, they could be saved. But a new vaccine that did just that suggests the theory is wrong.

British researchers gave 64 patients with moderate Alzheimer’s disease an experimental vaccine designed to eliminate plaque from their brains. Some patients were followed for up to six years.

Autopsies on seven patients who died of Alzheimer’s during the study showed that nearly all of the sticky beta-amyloid protein thought to be dangerous had been removed. But all patients still had severe dementia.

“It may be that these toxic plaques trigger the neurodegeneration, but don’t have an ongoing role,” said Clive Holmes of the University of Southampton, lead author, in a press statement. The study was published Friday in the medical journal, The Lancet.

The study was paid for by the Alzheimer’s Research Trust, a British charity.

Alzheimer’s disease is the most common cause of dementia and affects about 25 million people worldwide.

Other experts said that the study’s findings pointed to a major gap in our understanding of the disease. Doctors have never been sure whether the brain plaques are the cause of Alzheimer’s disease or just a side effect.

“We still don’t have enough understanding of what we should target,” said Dr. Bengt Winblad, director of the Alzheimer’s Centre at Sweden’s Karolinska Institute. Winblad was not connected to the study.

Aside from the plaque build-up, scientists also think that tangles of another brain protein called tau play a major role in Alzheimer’s. Because those tangles form later than the plaque, some experts think they should be the focus instead.

“It may be harder to get a response from targeting plaque because that forms years before people actually have Alzheimer’s,” said Dr. Simon Lovestone, professor of Old Age Psychiatry at King’s College in London. “By the time you do something, it may be too late.”

Winblad said there was a better connection between brain tangles and Alzheimer’s symptoms, but that no studies so far had looked at whether removing tangles might improve or even reverse Alzheimer’s disease in patients.

Still, experts say that attacking toxic plaque in the brain shouldn’t be abandoned just yet, since the formation of such plaques might be what sparks Alzheimer’s disease in the first place.

“Removal of the initial motor for the disease might slow progression,” wrote Peter H. St. George-Hyslop and John C. Morris of the University of Cambridge and the University of Toronto in an accompanying commentary in the Lancet.

Salon provides breaking news articles from the Associated Press as a service to its readers, but does not edit the AP articles it publishes.

Copyright 2008 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

“Learn to Manage Common Behavior Problems” (anger, hallucinations, nighttime wakefulness)

This will be of interest to those dealing with dementia (not only Alzheimer’s Disease) and related behavioral problems.

This guide is titled “Learn to Manage Common Behavior Problems.”  The problems addressed include:

  • wandering
  • rummaging around or hiding things
  • belligerence,  anger or aggressive behavior
  • hallucinations, illusions and paranoia
  • nighttime wakefulness and other sleep problems
  • refusing to eat

Though the guide is focused on Alzheimer’s caregivers, Lewy body dementia and other caregivers are challenged by these same problems.

You can find the guide online here:

www.helpguide.org/elder/alzheimers_behavior_problems.htm

I’ve copied some excerpts below.  (I read about this online resource tonight on a caregiver discussion group.)

Robin

————————

Excerpts from

Alzheimer’s Behavior Management:
LEARN TO MANAGE COMMON BEHAVIOR PROBLEMS
HelpGuide
December 19, 2007

…Most behavior problems pose serious difficulties for the person trying to provide care. Management of this behavior will require the caregiver to modify the home environment and change communication styles.

In This Article:
Management of wandering
Management of rummaging around or hiding things
Management of belligerence, anger or aggressive behavior
Management of hallucinations, illusions and paranoia
Management of nighttime wakefulness and other sleep problems
Management of refusing to eat
Related links

 

Management of belligerence, anger or aggressive behavior
Following are some ideas about caring for an aggressive Alzheimer’s patient. Consider each idea independently of the others.

Don’t confront the person or try to discuss the angry behavior. The person with dementia cannot reflect on their unacceptable behavior and cannot learn to control it.

Do not initiate physical contact during the angry outburst. Often, physical contact triggers physical violence in the patient.

Provide the person with a “time-out” away from you. Let them have space to be angry by themselves. Withdraw in the direction of a safe exit.

Distract the person to a more pleasurable topic or activity.

Look for patterns in the aggression. Consider factors such as privacy, independence, boredom, pain, or fatigue. Avoid those activities or topics that anger the person. To help find any patterns, you might keep a log of when the aggressive episodes occur.

If the person gets angry when tasks are too difficult for them, break down tasks into smaller pieces.

Minimize stress and novelty.

Maintain calm within yourself. Getting anxious or upset in response may escalate the aggressiveness.

Let the person play out the aggression. Just be sure that you are safe and that they are safe themselves.

Get help from others during the activities that anger the patient.

Don’t take the aggressiveness personally.

Management of hallucinations, illusions or paranoia
Hallucinations can be the result of failing senses. Unidentifiable sounds, shadows, and highly contrasting colors all can become the basis for fantasy. Decrease the number of things in the environment that can be misinterpreted as something else, such as patterned wallpaper or bright, contrasting surfaces or objects. Increase lighting so that there are few shadows while avoiding glare, and remove or cover mirrors if they cause problems. Maintaining sameness in the environment may also help reduce hallucinations. Also, violent movies or television can contribute to paranoia – avoid letting the patient watch disturbing programs.

When hallucinations or illusions do occur, don’t argue about what is real and what is fantasy. Discuss the patient’s feelings relative to what they imagine they see. Respond to the emotional content of what the person is saying, rather than to the factual/fictional content.

Medications can sometimes help to reduce hallucinations, so seek professional advice if you are concerned about this problem.

Management of nighttime wakefulness and other sleep problems
Brain disease often disrupts the sleep-wake cycle. Alzheimer’s patients may have wakefulness, disorientation, and confusion beginning at dusk and continuing throughout the night. This is called “sundowning.” There are two aspects to sundowning. First, confusion, over-stimulation, and fatigue during the day may result in increased confusion, restlessness, and insecurity at night. And second, some Alzheimer’s patients have fear of the dark, perhaps because of the lack of familiar daytime noises and activity. The patient may seek out security and protection at night to alleviate their discomfort.

Following are some strategies to reduce nighttime restlessness:

Improve sleep hygiene

Physical activities will help the person feel more tired at bedtime. Walk with the person during the day. If the person seems very fatigued during the day, give them a short rest in the afternoon to regain their composure. This can lead to a better night’s sleep. But don’t let them sleep too long – too much daytime napping can increase nighttime wakefulness. Also, limit the patient’s caffeine intake.

Be consistent with the time for sleeping, and keep a routine for getting ready for bed.

Create a calm atmosphere for sleeping

Give the person a bath and some warm milk before bed. Provide a comfortable bed, reduce noise and light, and play soothing music to help them get to sleep.

Close the curtains and leave a night light on all night. Some people with dementia imagine things in the dark and become upset. Stuffed animals or a pet may soothe the patient and allow them to sleep.

Have the person use the toilet right before bedtime. Place a commode next to the bed for nighttime urination. Walking to the bathroom in the middle of the night may wake the person up too much, and then they can’t get back to sleep.

The person may prefer to sleep in a chair or on the couch, rather than in bed. Furniture must be designed so that the patient won’t fall out while sleeping.

Resolve common problems
If the patient paces during the night, make sure that the primary daytime caregiver can sleep. This requires either a very safe room for the patient to pace in, or else another caregiver who takes over at night. You need your rest, too. Do not restrain the patient in bed, but consider a hospital bed with guard rails in the later stages of Alzheimer’s.
If night wakefulness has gotten too hard for you to manage, consult with a doctor if you wish to try administering sleeping pills.

 

Doug Russell, L.C.S.W., Suzanne Barston, and Monika White, Ph.D., contributed to this article. Last modified on: 12/19/07.

“Antipsychotics Dangerous for Elderly With Dementia”

This post will be of interest to those dealing antipsychotics (such as Haldol, Seroquel, or Risperdal) in the elderly with dementia.  Many with Lewy Body Dementia take this type of medication.  I have heard of a few people with Progressive Supranuclear Palsy, Corticobasal Degeneration, and even Multiple System Atrophy taking this type of medication.

HealthDay News (at everydayhealth.com) published a news article earlier this week on a new study showing that:

“Elderly people with dementia who are given antipsychotics, even for a very short period of time, are more likely to end up in the hospital or even die, new research shows.”

This is some follow-up to Canadian research published in June ’07 on the same subject (PubMed ID#17548409).  (Many of the researchers are the same on the two studies.)

The news article included reference to an Alzheimer’s Association (alz.org) publication on using antipsychotics in those with AD.  This publication is worth reading:

www.alz.org/national/documents/statements_antipsychotics.pdf

There is an FDA “black box” warning on the atypical antipsychotics.  You can find the April ’05 FDA warning on fda.gov at:

www.fda.gov/cder/drug/advisory/antipsychotics.htm

The HealthDay News article follows.  Below that is the abstract of the medical journal article.

Robin

————————–

tinyurl.com/5xuj95

Antipsychotics Dangerous for Elderly With Dementia
HealthDay News
Published: 05/27/08

MONDAY, May 26 (HealthDay News) — Elderly people with dementia who are given antipsychotics, even for a very short period of time, are more likely to end up in the hospital or even die, new research shows.

However, the problems underlying the need for such medications, behavioral problems such as aggression and agitation, are very real, and the alternatives to antipsychotics are limited, the researchers added.

“A misreading of the findings would be we don’t need to do something for these nursing home residents,” said study author Dr. Gary J. Kennedy, head of geriatric psychiatry for Montefiore Medical Center in New York City.

Many experts feel behavioral interventions should be tried first and antipsychotics used as a last resort, “when the behavior or the psychiatric symptoms are really out of control and causing complete distress not only for the person suffering from Alzheimer’s, but for caregivers all around them,” said Maria Carrillo, director of medical and scientific affairs at the Alzheimer’s Association in Chicago. “It’s important to work these things out with the physician and, of course, do follow-up very closely together, so you can make sure these antipsychotics are having the effect you want and, if not, discontinue them immediately.”

The findings were published in the May 26 issue of the Archives of Internal Medicine.

Antipsychotic drugs are commonly used to treat some of the behavioral complications of dementia, including delirium.

Newer antipsychotic medications such as Zyprexa (olanzapine) and Risperdal (risperidone) have been available for about a decade and have largely replaced their older counterparts.

Researchers from the Institute for Clinical Evaluative Sciences in Ontario, Canada, compared 20,682 older adults with dementia living in the community with 20,559 older adults with dementia living in a nursing home between April 1, 1997, and March 31, 2004.

Each group was divided into three subgroups: those not receiving any antipsychotics, those taking newer antipsychotics, and those taking older antipsychotics such as Haldol (haloperidol).

According to information gleaned from medical records, community-dwelling adults who had recently received a prescription for a newer antipsychotic medication were 3.2 times more likely than individuals who had received no antipsychotic therapy to be hospitalized or to die during 30 days of follow-up.

Those who received older antipsychotic therapy were 3.8 times more likely to have such an event, relative to their peers who had received no antipsychotic therapy.

A similar pattern, albeit less dramatic, emerged in the nursing home group. Individuals taking older antipsychotics were 2.4 times more likely to be hospitalized or die, while those taking newer drugs were 1.9 times more likely to die or be hospitalized during the 30 days of follow-up.

The study does, however, have its limitations. “It’s a carefully done study,” Kennedy said. “One flaw is that the [participants] weren’t randomly administered antipsychotics. There was some reason they were given an antipsychotic, such as aggression or agitation. It may have been done if they were recently admitted to the nursing home as part of the adjustment process.

Indeed, the authors acknowledged that about 17 percent of patients entering nursing homes start taking an antipsychotic within 100 days.

“For any of us, moving is like being sick. It takes a while to recover,” Kennedy said. “We need other sets of interventions besides medications. What that implies is more staffing and better training for staff, and that may not be a whole lot more expensive than medicines.”

———————————–

Here’s the abstract of the medical journal article:

Archives of Internal Medicine. 2008 May 26;168(10):1090-6.

Antipsychotic therapy and short-term serious events in older adults with dementia.

Rochon PA, Normand SL, Gomes T, Gill SS, Anderson GM, Melo M, Sykora K, Lipscombe L, Bell CM, Gurwitz JH.
Department of Medicine, University of Toronto, Canada.

BACKGROUND: Antipsychotic therapy is widely used to treat behavioral problems in older adults with dementia. Cohort studies evaluating the safety of antipsychotic therapy generally focus on a single adverse event. We compared the rate of developing any serious event, a composite outcome defined as an event serious enough to lead to an acute care hospital admission or death within 30 days of initiating antipsychotic therapy, to better estimate the overall burden of short-term harm associated with these agents.

METHODS: In this population-based, retrospective cohort study, we identified 20 682 matched older adults with dementia living in the community and 20 559 matched individuals living in a nursing home between April 1, 1997, and March 31, 2004. Propensity-based matching was used to balance differences between the drug exposure groups in each setting. To examine the effects of antipsychotic drug use on the composite outcome of any serious event we used a conditional logistic regression model. We also estimated adjusted odds ratios using models that included all covariates with a standard difference greater than 0.10.

RESULTS: Relative to those who received no antipsychotic therapy, community-dwelling older adults newly dispensed an atypical antipsychotic therapy were 3.2 times more likely (95% confidence interval, 2.77-3.68) and those who received conventional antipsychotic therapy were 3.8 times more likely (95% confidence interval, 3.31-4.39) to develop any serious event during the 30 days of follow-up. The pattern of serious events was similar but less pronounced among older adults living in a nursing home.

CONCLUSIONS: Serious events, as indicated by a hospital admission or death, are frequent following the short-term use of antipsychotic drugs in older adults with dementia. Antipsychotic drugs should be used with caution even when short-term therapy is being prescribed.

PubMed ID#: 18504337  (see pubmed.gov for the abstract)

“Compassionate Communication” – do’s and don’ts

Recently I attended a workshop on dementia caregiving.  This wonderful handout on compassionate communicate was shared.  Though written by an Alzheimer’s support group leader and addressed to caregivers of those with “memory impairment,” the suggestions of “do’s” and “don’ts” apply to all dementia types, even without memory impairment.

Here’s a link to the handout:

www.ocagingservicescollaborative.org/wp-content/uploads/2013/03/Compassionate-Communication-with-the-Memory-Impaired.pdf

Compassionate Communication with the Memory Impaired
Liz Ayres, Alzheimer’s Support Group Leader, former Caregiver, Orange County, CA
Copyright 2008

[Editor’s Note, 2013: handout link from 2008 no longer working.]

I’ve copied much of the handout below.  Page 2 of the handout contains lots of examples.

Robin


Compassionate Communication with the Memory Impaired
Liz Ayres, Alzheimer’s Support Group Leader, former Caregiver, Orange County, CA
©1995, 2001, 2005, 2007, 2008

DON’T

Don’t reason.
Don’t argue.
Don’t confront.
Don’t remind them they forget.
Don’t question recent memory.
Don’t take it personally.

DO

Give short, one sentence explanations.

Allow plenty of time for comprehension, then triple it.

Repeat instructions or sentences exactly the same way.

Eliminate ‘but’ from your vocabulary; substitute ‘nevertheless.’

Avoid insistence. Try again later.

Agree with them or distract them to a different subject or activity.

Accept the blame when something’s wrong (even if it’s fantasy.)

Leave the room, if necessary, to avoid confrontations.

Respond to the feelings rather than the words.

Be patient and cheerful and reassuring. Do go with the flow.

Practice 100% forgiveness. Memory loss progresses daily.

My appeal to you: Please elevate your level of generosity and graciousness.

REMEMBER

You can’t control memory loss, only your reaction to it. Compassionate communication will significantly heighten quality of life. They are not crazy or lazy. They say normal things, and do normal things, for a memory impaired, dementia individual. If they were deliberately trying to exasperate you, they would have a different diagnosis. Forgive them…always. For example: they don’t hide things; they protect them in safe places…and then forget. Don’t take ‘stealing’ accusations personally.

Their disability is memory loss. Asking them to remember is like asking a blind person to read. (“Did you take your pills?” “What did you do today?”) Don’t ask and don’t test memory! A loss of this magnitude reduces the capacity to reason. Expecting them to be reasonable or to accept your conclusion is unrealistic. (“You need a shower.” “Day care will be fun.” “You can’t live alone.”) Don’t try to reason or convince them. Give a one sentence explanation or search for creative solutions. Memory loss produces unpredictable emotions, thought, and behavior, which you can alleviate by resolving all issues peacefully. Don’t argue, correct, contradict, confront, blame or insist.

Reminders are rarely kind. They tell the patient how disabled they are––over and over again. Reminders of the recent past imply, “I remember, I’m okay; you don’t, you’re not.” Ouch! Refer only to the present or the future. (If they’re hungry, don’t inform them they ate an hour ago, offer a snack or set a time to eat soon.) They may ask the same question repeatedly, believing each time is the first. Graciously respond as if it’s the first time. Some days they seem normal, but they’re not. They live in a different reality. Reminders won’t bring them into yours. Note: For vascular dementia, giving clues may help their recall. If it doesn’t work, be kind…don’t remind.

Ethical dilemmas may occur. If, for instance, the patient thinks a dead spouse is alive, and truthful reminders will create sadness, what should you do? To avoid distress, try these ways of kindness: 1) distract to another topic, or 2) start a fun activity, or 3) reminisce about their spouse, “I was just thinking about ___. How did you meet?” or you might try, “He’s gone for a while. Let’s take our walk now.”

Open ended questions (“Where shall we go?” “What do you want to eat/wear/do?”) are surprisingly complex and create anxiety. Give them a simple choice between two items or direct their choice, “You look great in the red blouse.”

They are scared all the time. Each patient reacts differently to fear. They may become passive, uncooperative, hostile, angry, agitated, verbally abusive, or physically combative. They may even do them all at different times, or alternate between them. Anxiety may compel them to shadow you (follow everywhere). Anxiety compels them to resist changes in routine, even pleasant ones. Your goal is to reduce anxiety whenever possible. Also, they can’t remember your reassurances. Keep saying them.

 

Photophobia, VH, and RBD in PSP+CBD (Mayo Rochester study)

This is a rather weak study because they looked at 10 patients with the clinical diagnosis of PSP and 11 patients with the clinical diagnosis of CBD. No pathological confirmation was available. Their findings included:

* “Photophobia occurred in all 10 (100%) PSP patients vs 2 (18%) patients with clinically suspected CBD (p=0.0002).” And: “The presence of photophobia is significantly more frequent in clinically diagnosed PSP than CBD and can be used as a feature in differentiating between the two diseases in clinical practice.”

Every PSPer I’ve met has photophobia and some (but not all) of the CBDers I’ve met have photophobia.

* “Visual hallucinations and RBD occurred in patients with PSP and CBD but were rare occurrences (5% for each symptom).” And: “Visual hallucinations and RBD occur infrequently in PSP and CBD and are not useful symptoms in clinical differentiation.”

I usually hear “photophobia” called “photo sensitivity.” Whenever I was in the hospital or skilled nursing facility with my dad, I’d always close the blinds/curtains and, if there was an overhead light on, we’d put sunglasses on dad or a washcloth over his eyes to block out the light. “Photophobia” is extreme sensitivity or aversion to sunlight and any other light.

Robin

Parkinsonism & Related Disorders. 2008 Mar 5 [Epub ahead of print]

Photophobia, visual hallucinations, and REM sleep behavior disorder in progressive supranuclear palsy and corticobasal degeneration: A prospective study.

Cooper AD, Josephs KA.
Department of Neurology, Mayo Clinic, Rochester, MN.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) have overlapping clinical features that can make clinical distinction between these two entities difficult. The present study compared the frequency of photophobia, visual hallucinations, and REM sleep behavior disorder (RBD) in patients clinically diagnosed with PSP to those clinically suspected to have CBD. Photophobia occurred in all 10 (100%) PSP patients vs 2 (18%) patients with clinically suspected CBD (p=0.0002). Visual hallucinations and RBD occurred in patients with PSP and CBD but were rare occurrences (5% for each symptom). The presence of photophobia is significantly more frequent in clinically diagnosed PSP than CBD and can be used as a feature in differentiating between the two diseases in clinical practice. Visual hallucinations and RBD occur infrequently in PSP and CBD and are not useful symptoms in clinical differentiation.

PubMed ID#: 18328771 (see pubmed.gov for abstract only)


I received a copy of this full article today. In my earlier post, after reading the abstract only, I concluded that no cases in this Mayo Rochester study had been pathologically-confirmed. This is incorrect. The full article notes that “Ten patients had PSP, two with pathologic confirmation, and 11 patients had CBS, one with pathologic confirmation.”

These patients (and their significant others) were questioned regarding photophobia. “The question regarding photophobia emphasized discomfort as a result of light exposure as opposed to frequent eye closing or lack of eye opening. This distinction is important since both blepharospasm and apraxia of eye opening can be present in these disorders.”

The findings were: “Photophobia occurred in all 10 (100%) PSP patients vs 2 (18%) CBS patients. The mean time between when the patient first reported photophobia and disease onset was 3.1 years.” Based upon this, the authors argue that “the presence of photophobia may help clinicians to better differentiate between PSP and CBS on a clinical basis…”

Interestingly, of the 2 CBS patients with photophobia, one of these was pathologically-confirmed as CBD. And, “both CBS patients with photophobia were two of only three CBS patients with vertical gaze palsy suggesting pathological involvement of brainstem nuclei in these two subjects.”

The authors admit that they need more pathologically-confirmed cases.

This finding was surprising: “Blepharospasm was noted in only one patient in this series. He was one of the two CBS patients with photophobia and was pathologically confirmed to have CBD.” It seems that in our local support group blepharospasm is more common.

One note to the CBD folks: This article says that the term CBS (corticobasal syndrome) is used for the clinical entity while CBD (corticobasal degeneration) is used for the pathologic entity.

See below for some excerpts to this short article.

Robin

Here are some excerpts that may be of interest:

Introduction
“Progressive supranuclear palsy (PSP) and corticobasal de-
generation (CBD) are neurodegenerative disorders that display
some overlapping clinical features. The core clinical features
of PSP include vertical gaze palsy, axial more than appendic-
ular rigidity, and early postural instability. The core clinical
features of CBD include asymmetric appendicular rigidity and
cortical dysfunction including apraxia of limb. The term corti-
cobasal syndrome (CBS) has been applied to the clinical
entity, while CBD refers to the pathologic entity.”

“When the cardinal features of these two diseases are present
at disease onset, diagnosis may be relatively straightforward.
However, clinical features of these two diseases often overlap
and some of the cardinal features may not occur until later in
the disease course. These atypical disease presentations can
present a diagnostic dilemma, which may make it difficult for
clinicians to predict disease progression. Therefore, additional
clinical features that could distinguish PSP from CBD would be
helpful in clinical practice. Photophobia has been described in
PSP but not CBD to our knowledge. Visual hallucinations and
REM sleep behavior disorder (RBD) have not been emphasized
in either PSP or CBD.We conducted a study to determine
the frequency of photophobia, visual hallucinations, and RBD
in these two disease populations.”

Methods
“One movement disorders specialist (KAJ) evaluated all
patients with features suggestive of PSP and CBD from 2003
to 2006 at a single medical institution.”

“We questioned patients and their significant others regarding
the presence of photophobia, visual hallucinations, and RBD.
The question regarding photophobia emphasized discomfort
as a result of light exposure as opposed to frequent eye
closing or lack of eye opening. This distinction is important
since both blepharospasm and apraxia of eye opening can be
present in these disorders. Only well-formed visual hallucina-
tions that were spontaneous and not associated with medica-
tion use were considered. REM sleep behavior disorder was
considered present if the patient’s bed partner reported
abnormal limb movements during sleep that were disruptive or
injurious to either the bed partner or the patient.”

Results
“Ten patients had PSP, two with pathologic confirmation, and
11 patients had CBS, one with pathologic confirmation. The
median ages at disease onset in PSP and CBS were 66
(range 59-77) and 65 (range 49-91)…”

“Based on clinical criteria for PSP, four patients were clas-
sified as possible, four as probable, and two were definite
(i.e. pathologically confirmed).”

“Photophobia occurred in all 10 (100%) PSP patients vs 2
(18%) CBS patients. The mean time between when the
patient first reported photophobia and disease onset was
3.1 years.”

“Blepharospasm was noted in only one patient in this series.
He was one of the two CBS patients with photophobia and
was pathologically confirmed to have CBD.”

“Visual hallucinations occurred in 1 (5%) PSP patient and
RBD occurred in 1 (5%) CBS patient. The visual hallucina-
tions occurred in a PSP patient taking Levodopa/Carbidopa.
… The hallucinations continued despite reduction of the
Levodopa/Carbidoba and, unfortunately, the patient died
before further dose reductions could be made.”

“The CBS patient with RBD had symptoms consisting of
talking and performing exercising movements usually during
the first 1-2 h of sleep.”

Discussion
“The present study demonstrates a significant difference in
the frequency of photophobia in patients with PSP com-
pared to those with CBS. This result suggests that the
presence of photophobia may help clinicians to better dif-
ferentiate between PSP and CBS on a clinical basis, and
may be a helpful feature in predicting underlying pathology.”

“The pathophysiology of photophobia is not entirely under-
stood. Studies have pointed to the trigeminal nerve as one
necessary component for photophobia. … Other studies
have suggested a role of the optic nerve and its connec-
tions with the pretectal nuclei. Indeed, it may be an inter-
action of these two pathways that produce photophobia.
The corresponding subcortical location of the trigeminal
and optic nerve connections and typical subcortical loca-
tion of PSP pathology, such as the superior colliculi, may
explain the high incidence of photophobia found in our PSP
population. The subcortical location of PSP pathology con-
trasts with the more cortical location of pathology found in
CBD and may explain the relatively low frequency of photo-
phobia found in patients with CBS in our study. In fact, both
CBS patients with photophobia were two of only three CBS
patients with vertical gaze palsy suggesting pathological
involvement of brainstem nuclei in these two subjects.”

“Visual hallucinations and RBD were rare occurrences in
each population making them unhelpful in clinical differen-
tiation between PSP and CBS. The low occurrence of RBD
is not surprising since this clinical phenomenon has been
shown to be suggestive of underlying alpha-synuclein path-
ology, and both PSP and CBD are characterized by the
deposition of the microtubule associated protein tau
(MAPT) and not alpha-synuclein pathology.”

“Litvan et al. showed that the presence of gait abnormality,
bilateral bradykinesia, and moderate to severe vertical
supranuclear gaze palsy help to distinguish PSP from
CBS. Their study was based on pathologically confirmed
cases of these two diseases. Since our study is based
on clinical and/or pathologic criteria, we cannot conclude
that the presence of photophobia will definitely predict
pathologic confirmation of PSP. However, 15% of our
cases were pathologically confirmed and prior studies
have shown that more than 75% of clinically diagnosed
PSP patients have PSP pathology.”

“The results of our study suggest that patients suspected
to have PSP or CBD should be questioned regarding the
presence or absence of photophobia as part of routine
questioning. … In this study, we demonstrate for the first
time that the presence of photophobia may be an addi-
tional useful clinical feature to differentiate PSP from
CBD.”