Lewy Body Dementia
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Psychiatric Symptoms Also Helped by Cholinesterase Inhibitor: A very small DB PC study of 25 patients with Lewy Body Dementia found scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician's Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Efficacy and safety of galantamine in patients with dementia with lewy bodies: a 12-week interim analysis. Edwards KR, Hershey L, Wray L, Bednarczyk EM, Lichter D, Farlow M, Johnson S. Dement Geriatr Cogn Disord. 2004;17 Suppl 1:40-8

Lewy Body Dementia: 15-20% of all autopsy-confirmed dementias in old age. Characteristic histopathological changes are intracellular Lewy bodies and Lewy neurites, with abundant senile plaques but sparse neurofibrillary tangles. Core clinical features are fluctuating cognitive impairment, persistent visual hallucinations and extrapyramidal (EPS) motor symptoms (parkinsonism). One of these core features has to be present for a diagnosis of possible LBD, and two for probable LBD. Supportive features are repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, delusions and hallucinations in other modalities. cholinesterase inhibitors can offer a safe alternative for the symptomatic treatment of cognitive and neuropsychiatric features. Dementia with Lewy bodies - diagnosis and treatment. Mosimann U, McKeith I. Swiss Med Wkly 2003 Mar 8;133(9-10):131-142

Lewy Body Dementia Signs: Lewy patients more inattention, distractible, impaired task establishment and shifting, incoherence, confabulatory, perseveration, intrusions (incorporating irrelevant environmental cues into talk) than in AD patients. J Neuro, Neurosurg, Psych 02;72:602

LBD More Wandering, Visual Hallucinations, Non-Specific Tremor: Autopsy study of 13 LBD vs 12 AD patients. St. Louis. J Am Med Dir Assoc. 2001 Jul-Aug;2(4):146-148

Short Screening Subset Test for MMSE: 6 item test with 3 score correlated well with MMSE score of 23 or lower for dx of dementia or cognitive impairment. Tested on Afro-Am community sample of 343 women aver 74yo with 4% dementia, 25% impaired. Also on over 600 in alzheimer rx. [email protected] Christopher M. Callahan, MD Indiana University Center for Aging Research; Medical Care 2002; 40(9):771-781

EPS Predicts Lewy Bodies and Early Death in AD: EPSs in patients with AD indicates worse prognosis and may be related to underlying LBs. The presence of EPSs is a strong predictor of LBs. Patients with EPS or psychiatric symptoms die faster. U Mich. Arch Neurol 2002 Apr;59(4):588-93. 

Differential Diagnosis From Alzheimer's: Daytime Drowsiness, Lethargy, Sleep, and Staring: reliable method for distinguishing Alzheimer's disease (AD) from dementia with Lewy bodies (DLB) and normal aging, according a new study from the January 27, 2004, Neurology, Tanis J. Ferman. Lewy bodies are round collections of brain proteins which are the pathological hallmark of Parkinson's disease in the substantia nigra. In DLB, Lewy bodies are also found in brain's cortex. DLB accounts for as much as 20 to 35 percent of U.S. dementia. Fluctuating cognition include episodes of confusion, excessive sleepiness, a waxing and waning of cognition, inattention, incoherent speech and varying ability to perform tasks. When this occurs, family members often describe their loved ones as "zoned out," or "not with us." Four characteristics significantly distinguished 70 patients with DLB from 70 persons with AD and 200 normal elderly controls: daytime drowsiness and lethargy despite getting enough sleep the night before; falling asleep two or more hours during the day; staring into space for long periods and episodes of disorganized speech.

Autonomic Dysfunction Common: Twenty patients with dementia with Lewy bodies (DLB) were compared to 20 age-matched multiple system atrophy (MSA) and Parkinson disease (PD) patients. In DLB, mean age at onset of autonomic symptoms was age 70. Orthostatic symptoms were common and orthostatic hypotension occurred in 10/20 DLB, 17/20 MSA, and 1/20 PD patients (p = 0.023, 0.003). CASS-sudomotor for DLB, MSA, and PD were 1.6, 2.5, and 0.9 (p < 0.00001). CASS-cardiovagal were 1.4, 2.1, and 0.7 (p < 0.00001). CASS-adrenergic function were 2.4, 3.5, and 0.5 (p < 0.00001). Total CASS were 5.2, 8.1, and 2.2 (p < 0.00001). The most common pattern of TST in DLB was distal anhidrosis. Six patients needed medication to maintain blood pressure and five had good response. Autonomic dysfunction in dementia with Lewy bodies. Thaisetthawatkul P, Boeve BF, Benarroch EE, Sandroni P, Ferman TJ, Petersen R, Low PA.Mayo Clinic. Neurology. 2004 May 25;62(10):1804-9

Synuclein Missense Mutations in Lewy Bodies and Familial Parkinsons: Alpha-Synuclein is a presynaptic protein that is implicated in the pathogenesis of various neurodegenerative diseases. Missense mutations in the alpha-synuclein gene are linked to familial cases of Parkinson's disease (PD), and it has further been shown that alpha-synuclein is a major constituent of the Lewy bodies in sporadic PD and dementia with Lewy body (DLB). U Saarland. alpha-Synuclein, Abeta and Alzheimer's disease. Wirths O, Bayer TA. Prog Neuropsychopharmacol Biol Psychiatry 2003 Feb;27(1):103-8

Septin4 Also Involved with Synuclein and Synphilin: alpha-Synuclein-positive cytoplasmic inclusions are a pathological hallmark of several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Here we report that Sept4, a member of the septin protein family, is consistently found in these inclusions, while five other septins (Sept2, Sept5, Sept6, Sept7, and Sept8) are not found in these inclusions. Sept4 and alpha-synuclein can also be co-immunoprecipitated from normal human brain lysates. When co-expressed in cultured cells, FLAG-tagged Sept4 and Myc-tagged alpha-synuclein formed detergent-insoluble complex, and upon treatment with a proteasome inhibitor, they formed Lewy body-like cytoplasmic inclusions. The tagged Sept4 and alpha-synuclein synergistically accelerated cell death induced by the proteasome inhibitor, and this effect was further enhanced by expression of another Lewy body-associated protein, synphilin-1, tagged with the V5 epitope. Moreover, co-expression of the three proteins (tagged Sept4, alpha-synuclein, and synphilin-1) was sufficient to induce cell death. These data raise the possibility that Sept4 is involved in the formation of cytoplasmic inclusions as well as induction of cell death in the alpha-synuclein-associated neurodegenerative disorders. Association of the cytoskeletal GTP-binding protein Sept4/H5 with cytoplasmic inclusions found in Parkinson's disease and other synucleinopathies. Ihara M, Tomimoto H, Kitayama H, Morioka Y, Akiguchi I, Shibasaki H, Noda M, Kinoshita M. Kyoto Univ., J Biol Chem 2003 Apr 14

Dementia with Neurofilament Inclusions: This may be a different type of dementia characterized clinically by early-onset with frontal lobe signs, focal atrophy of the frontal and temporal lobes, and microscopically by the presence in many brain regions of intraneuronal, cytoplasmic, neurofilament inclusions. The neuronal inclusions are immunoreactive to all three molecular weight neurofilament subunits: heavy (NF-H), light, and medium subunits, including the phosphorylated and non-phosphorylated forms of NF-H. Prion protein and beta-amyloid deposits were absent. The inclusions do not contain tau or alpha-synuclein protein aggregates known to characterize many neurodegenerative disorders. Patients with a novel neurofilamentopathy: dementia with neurofilament inclusions. Cairns NJ, Perry RH, Jaros E, Burn D, McKeith IG, Lowe JS, Holton J, Rossor MN, Skullerud K, Duyckaerts C, Cruz-Sanchez FF, Lantos PL. University of Penn. Neurosci Lett 2003 May 8;341(3):177-80

Donepezil Helps Lewy Body Dementia Hallucinations: In an open study of 9 patients treated with 5-10 mg/day for 8-24 weeks, it was found that hallucinations were markedly reduced in 8 of 9 while on donepezil, cognition improved in 6, but 3 experienced a worsening of parkinsonism. Internatl Psychogeriatrics 98;10:229