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 DLB Overview + Distinguishing DLB and AD (Ferman/Boeve '07) 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post DLB Overview + Distinguishing DLB and AD (Ferman/Boeve '07)
This newly-published abstract indicates that "Neurocognitive patterns, psychiatric features, extrapyramidal signs, and sleep disturbance are helpful in differentiating DLB from AD early in the disease course. Differences in the severity of cholinergic depletion and type/distribution of neuropathology contribute to these clinical differences." I will attempt to get this full article. Boeve has another article published in this same journal on Parkinson-related dementias. (Boeve is also a lead researcher in CBD, another Parkinson-related dementia.)

Neurologic Clinics. 2007 Aug;25(3):741-60.

Dementia with lewy bodies.

Ferman TJ, Boeve BF.
Department of Psychiatry & Psychology, Mayo Clinic, Jacksonville, FL 32224, USA.

The advent of new immunostains have improved the ability to detect limbic and cortical Lewy bodies, and it is evident that dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia, after Alzheimer's disease (AD). Distinguishing DLB from AD has important implications for treatment, in terms of substances that may worsen symptoms and those that may improve them. Neurocognitive patterns, psychiatric features, extrapyramidal signs, and sleep disturbance are helpful in differentiating DLB from AD early in the disease course. Differences in the severity of cholinergic depletion and type/distribution of neuropathology contribute to these clinical differences.

PubMed ID#: 17659188

Wed Aug 01, 2007 1:23 am

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
THANKS to fellow Forum member Patty, I was able to read this full article. It's a good overview of DLB.

One of the key points of the article is that we should be able to distinguish between early stage DLB and AD. Some excerpts on that point are:

"(Impaired) visual construction and attention plus preserved memory and naming skills distinguished DLB from AD (sensitivity of 83.3% and a specificity of 91.4%)."

"Memory difficulties, when present in early DLB, seem to be fairly mild and stand in direct contrast to the pronounced amnestic disturbance of AD. Neuropathologic and imaging studies also show significant atrophy in the hippocampus in AD, whereas patients who have DLB show little difference from normal controls."

"In a sample of nine cases of pure DLB, 57 of mixed DLB/AD, and 66 of pure AD, patients who had AD pathology performed worse on tasks of verbal memory, whereas patients who had LB pathology performed worse on tasks of visual spatial skills, and combined pathology affected visual spatial performance but not verbal memory."

"VH have been documented to occur in 59% to 85% of autopsy-confirmed DLB samples and in 11% to 28% of autopsy-confirmed AD samples. Autopsy studies reveal that VH are most likely to occur early in DLB disease course, whereas they tend to occur in the advanced stages of AD. In an autopsy study of DLB (n=41) and AD (n=70), a cutoff of 4 years for the onset of hallucinations relative to dementia onset improved the positive and negative predictive values of DLB to 81% and 79%, respectively." (VH = visual hallucinations)

"Results show that four items significantly differentiated DLB from AD, including (1) daytime drowsiness and lethargy, (2) daytime sleep of 2 or more hours, (3) staring into space for long periods, and (4) times when a patient’s flow of ideas seems disorganized, unclear, or not logical."

"When compared with AD, MRI voxel-based morphometry reveals that DLB has little cortical involvement but does show a discrete cluster of gray matter loss in the cholinergic-rich regions of the nucleus basalis of Meynert in the basal forebrain and dorsal

"(Cholinergic) depletion is a critical factor in the symptom manifestation of early DLB but may be less so in early AD. This highlights the importance of differentiating between early versus late stages of different dementias, because patients who have advanced AD may have similar clinical features as those who have early DLB."

"Clinical features that may be helpful in distinguishing early DLB from AD include neurocognitive presentation, VH, extrapyramidal signs, fluctuations, neuroleptic sensitivity, RBD, and dysautonomia."

Excerpts on other topics are:

"In general, the parkinsonism-associated with DLB tends to be less severe than that observed in PD or PDD, at least initially."

"One study of 14 patients who had DLB, 28 who had PD, and 30 who had PDD showed improvement in the Unified Parkinson’s Disease Rating Scale score for all three groups in response to levodopa but less so for the patients who had DLB."

"The underlying cause of hallucinations most likely is associated with the severe depletion of acetylcholine in DLB, but other neurotransmitter systems may have a contributory role, including dopamine and serotonin. ...Also, the dysregulation of rapid eye movement (REM) sleep in many patients who have DLB raises the possibility of intrusion of dream imagery into wakefulness as a potential mechanism."

The "usefulness" of fluctuating cognition as a "core clinical feature has been highly criticized."

"Patients who have DLB often have daytime drowsiness or somnolence. As such, ruling out known causes of daytime sleepiness, including medications and primary sleep disorders (ie, sleep apnea), is critical."

"(A) clinical history of RBD in the context of dementia with disproportionate visual deficits and relatively preserved memory and
naming is likely to represent the earliest stages of DLB."

"A comparison of...DLB, PD, and MSA shows that orthostatic hypotension is affected most severely in MSA, least severely in PD, and of intermediate severity in DLB. The DLB group tended to respond better to medications than the MSA group. The frequency of urinary symptoms and pattern of sweat loss in DLB was comparable to that of PD but much less than MSA."

"In a longitudinal study of 63 patients who had DLB and 252 who had AD, ...DLB was associated with increased risk of mortality. Extrapyramidal signs were a strong predictor of mortality."

"Increasing acetylcholine availability with cholinesterase inhibitors improves attention, hallucinations, and alertness in early DLB. ... Extrapyramidal side effects of cholinesterase inhibit ors are low, and it is recommended as a first-line treatment for DLB."

"Neuroleptic medication is frequently administered to patients with dementia for episodic confusion, hallucinations, delusions, and agitation. These clinical features are observed commonly in DLB, but there is convincing evidence that patients who have DLB can harbor neuroleptic sensitivity to traditional and to some atypical neuroleptics. Specifically, antipsychotic agents with D2 antagonism and anticholinergic properties precipitate or exacerbate extrapyramidal signs and cognitive impairment, respectively. Unfortunately, discontinuation of the neuroleptic does not necessarily lead to a reversal of the adverse reaction. There is a mixed literature on the relationship between atypical antipsychotics and cognition, but quetiapine has a better response profile overall in DLB relative to AD. Olanzepine does not seem to worsen parkinsonism, but its anticholinergic properties may exacerbate cognitive impairment." (quetiapine = Seroquel; olanzepine = Zyprexa)

"Levodopa-carbidopa is generally well tolerated in DLB, does diminish extrapyramidal signs and does not seem to precipitate a profound worsening of psychosis as seen in the dopamine agonists or amantadine."

To treat RBD, "Clonazepam at a very low dose usually is effective. Melatonin also may be effective, either as monotherapy or in conjunction with clonazepam."

"Excessive daytime sleepiness is challenging, and the first approach is to try to identify if the cause may be a medication side effect, mood, or a primary sleep disorder. Although psychostimulants would be expected to exacerbate hallucinations and delusions in DLB, experience has shown that daytime somnolence in some patients can be managed with agents, such as modafinil and methylphenidate." (modanfinil = Provigil; methylphenidate = Ritalin)

"Before treating hallucinations or delusions (false beliefs), it must be determined if these symptoms are harmful or distressing to patients."

Fri Aug 03, 2007 3:59 am
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