Dennis W. Dickson

DLB fluctuations: Specific features that reliably differentiate DLB from AD and normal aging

Objective: To determine whether certain aspects of fluctuations reliably distinguish dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) and normal aging. Methods: Participants included 200 community-dwelling cognitively normal elderly persons, 70 DLB patients, and 70 AD patients with collateral informants. A 19-item questionnaire was administered to the informants that queried about symptoms of fluctuations and delirium. Results: Fluctuations occur infrequently in nondemented elderly persons aged 58 to 98 years. In contrast, four characteristics of fluctuations were found to significantly differentiate AD from DLB. These composite features include daytime drowsiness and lethargy, daytime sleep of 2 or more hours, staring into space for long periods, and episodes of disorganized speech. The presence of three or four features of this composite occurred in 63% of DLB patients compared with 12% of AD patients and 0.5% of normal elderly persons. Informant endorsement of three or four of these items yielded a positive predictive value of 83% for the clinical diagnosis of DLB against an alternate diagnosis of AD. Endorsement of fewer than three items had a negative predictive value of 70% for the absence of a clinical diagnosis of DLB in favor of AD. The authors present evidence of test-retest reliability, convergent validity, and empirical verification with a separate cross-validation sample. Fluctuations were not associated with any particular combination of hallucinations, parkinsonism, or REM sleep behavior disorder. Conclusions: Based on informant report, disturbed arousal and disorganized speech are specific aspects of fluctuations in dementia with Lewy bodies that reliably distinguish dementia with Lewy bodies from Alzheimer’s disease and normal aging.

α-Synuclein pathology in the spinal cords of neurologically asymptomatic aged individuals

The authors assessed the frequency of spinal cord α-synuclein pathology in neurologically asymptomatic individuals older than 60 years of age (N = 106). Using α-synuclein immunohistochemistry, nine cases (8%) had incidental Lewy neurites in the intermediolateral column and at least some α-synuclein pathology in the dorsal motor nucleus of the vagus, locus ceruleus, and central raphe nucleus. Sparse α-synuclein pathology was also detected in the substantia nigra, basal forebrain, amygdala, or cortex in all but two cases.

Coexistent Lewy body disease in a case of “visual variant of Alzheimer’s disease”

Posterior cortical atrophy or the “visual variant” of Alzheimer’s disease is a clinical syndrome with visual agnosia, some or all the components of Balint’s syndrome, transcortical sensory aphasia, and Gerstmann’s syndrome.1 Although pathologically heterogeneous, several necropsy studies on patients with posterior cortical atrophy have shown Alzheimer’s disease pathology.1 We report a patient who presented with the features of posterior cortical atrophy who later developed mild parkinsonism, visual hallucinations, and delusions. Neuropathological evaluation revealed combined Alzheimer’s disease and Lewy body disease.nnA right handed retired diesel mechanic, with 12 years of formal education, was referred for evaluation of an “unusual dementia.” His difficulties started at the age of 58 with the insidious onset of visuospatial dysfunction. Initially he was not able to fill out bank deposit slips or write numbers correctly. He had been an avid reader but had to re-read material in order to comprehend it, and unsuccessfully used a card to keep his eyes focused when reading. He was not able to locate the refrigerator door handle until he groped over the surface to find it.nnHis wife revealed that when he was 61 he was having difficulties working as a mechanic. Also, he could not see other cars and obstacles while driving, and he stopped driving at the age of 63 after being involved in two motor vehicle …

Similarities between familial and sporadic autopsy-proven progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a relatively common neurodegenerative tauopathy clinically characterized by parkinsonism, axial rigidity, and supranuclear gaze palsy. Pathologic findings of PSP are neuronal loss, gliosis, and neurofibrillary tangles in basal ganglia, diencephalon, and brainstem; there is increasing recognition of clinicopathologic variants of PSP.1

LRRK2 (Leucine-Rich Repeat Kinase 2) Gene on PARK8 Locus in Families with Parkinsonism

It is estimated that about 10% to 30% of Parkinson’s disease (PD) cases are familial [1]. Eleven PD loci/mutations have already been identified [2] (Table 1). The PARK8 locus on chromosome 12p11.2-q13.1 was first found in 2002 in a large Japanese kindred known as the Sagamihara family [3]. The linkage analysis studies performed by our group on 21 caucasian families showed probable linkage to this locus in 10 kindreds [4]. In late April of 2004, we found the first mutation in the leucine-rich repeat kinase 2 (LRRK2) gene in family D (western Nebraska). Two weeks later the second mutation in this gene for family A (German-Canadian) [5] was discovered. Other groups have confirmed our discovery in a number of other families [6–9].