Joan M. Swearer

Troublesome and disruptive behaviors in dementia. Relationships to diagnosis and disease severity

Patients with dementia often manifest troublesome and disruptive behaviors in addition to intellectual impairments. This study evaluated behavioral disturbances in 126 demented patients examined sequentially, using questionnaires administered to primary caregivers to quantify the types and severity of behavioral disturbances. Eighty‐three percent of the patients exhibited one or more of the targeted behaviors. The most common troublesome and disruptive behaviors clustered into three categories: aggressive, ideational, and vegetative. The prevalence and severity of the behaviors increased with global severity of dementia, but did not differ in either frequency or type when patients with three diagnoses were compared: Alzheimers disease (AD), multi‐infarct dementia (MID), and mixed AD and MID (MIX). The occurrence and severity of the target behaviors correlated modestly with the severity of dementia. Impairments of mental status correlated weakly with only a single troublesome and disruptive behavior—assaultiveness.

Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees

The amyloid cascade hypothesis suggests that the aggregation and deposition of amyloid-β protein is an initiating event in Alzheimers disease (AD). Using amyloid imaging technology, such as the positron emission tomography (PET) agent Pittsburgh compound-B (PiB), it is possible to explore the natural history of preclinical amyloid deposition in people at high risk for AD. With this goal in mind, asymptomatic (n = 5) and symptomatic (n = 5) carriers of presenilin-1 (PS1) mutations (C410Y or A426P) that lead to early-onset AD and noncarrier controls from both kindreds (n = 2) were studied with PiB–PET imaging and compared with sporadic AD subjects (n = 12) and controls from the general population (n = 18). We found intense and focal PiB retention in the striatum of all 10 PS1 mutation carriers studied (ages 35–49 years). In most PS1 mutation carriers, there also were increases in PiB retention compared with controls in cortical brain areas, but these increases were not as great as those observed in sporadic AD subjects. The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not show the typical regional pattern of PiB retention observed in sporadic AD. Postmortem evaluation of tissue from two parents of PS1C410Y subjects in this study confirmed extensive striatal amyloid deposition, along with typical cortical deposition. The early, focal striatal amyloid deposition observed in these PS1 mutation carriers is often is not associated with clinical symptoms.

Incontinence and Troublesome Behaviors Predict Institutionalization in Dementia

Factors predicting the early institutionalization of demented patients were studied in 143 outpatients using univariate and multivariate life-table methods. Four types of factors were evaluated for prognostic value: severity of functional impairment, behavioral disorders, individual patient characteristics, and type of caregiver. After follow-up of 19 ± 12 months, 51 patients had been institutionalized. Increased global severity of dementia, the presence of troublesome and disruptive behaviors, and incontinence increased the likelihood of institutionalization. The best predictors of institutionalization were paranoia, aggressive behavior, and incontinence. Neither individual patient characteristics (age, education, and gender) nor caregiver relationship to the patient (male spouse, female spouse, and male or female child) influenced institutionalization. Since troublesome behavioral disorders are potentially treatable aspects of dementia leading to institutionalization, their management should be a major focus of therapy in dementia. (J Geriatr Psychiatry Neurol 1992;5:45–52).

Familial and sporadic Alzheimer's disease Neuropathology cannot exclude a final common pathway

Whether all etiologic forms of Alzheimers disease (AD) share a final common pathway is a major issue.We determined the severity and regional distribution of neuronal loss, amyloid plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs), and calculated the ratio of neuronal loss to NPs and NFTs in brains of 19 familial AD (FAD) patients with linkage to chromosome 14, six AD patients with mutations of chromosome 21 (codon 717 of the beta-amyloid precursor protein gene), and 11 sporadic AD (SAD) patients. There was no difference in the pattern of distribution of the various pathologic features or in the ratio of neuronal loss to NPs or NFTs in any AD group. However, FAD groups could be distinguished from SAD by the greater severity and the lack of influence of apolipoprotein E genotype on pathology. These differences may reflect differences in age at onset rather than different etiopathologic mechanisms. The similarity of pathologic findings in the different AD groups provides evidence for a final common pathophysiologic pathway in AD. NEUROLOGY 1996;46: 406-212

Familial Alzheimer disease: Decreases in CSF Aβ42 levels precede cognitive decline

CSF amyloid β-peptide 42 (Aβ42) levels in presymptomatic subjects with pathogenic mutations in the PS1 gene are significantly lower than in an age-matched control group. Consequently, in these subjects, there is a window of opportunity estimated as at least 4 to 12 years to evaluate the ability of any putative prophylactic therapy to decrease, arrest, or reverse abnormalities in Aβ42 metabolism many years before clinical symptoms of Alzheimer disease are otherwise likely to occur.

A topographic study of ERPs elicited by visual feature discrimination.

The functional properties and topographic distribution of event-related potential (ERP) components elicited by visual discrimination of orientation, spatial frequency, spatial location, and color were investigated. ERPs were recorded from 28 electrode sites from 16 adult subjects. Five ERP components were measured: N1 (peak latency = 160 ms), P2 (250 ms), anterior N2 (260 ms), posterior N2 (280 ms), and P3 (400 ms). N1 and P2 were more negative when a stimulus was a target, showing the selection negativity effect. Feature-specific effects on component amplitude or topography varied by component. N1 and P2 were sensitive to stimulus orientation and location. Anterior or posterior N2 was sensitive to orientation, spatial frequency, and location. P3 varied with orientation, but not with other stimulus features. Cross-task comparisons of ERPs to vertical line segments in the color, orientation, and location discrimination tasks indicated that P2 and N2, but not N1 and P3, were sensitive to changes in task-demand. These data provide topographic evidence that ERP components in the 160-400 ms time domain can be differentiated on the basis to processing of specific visual features, and reflect neurophysiologically distinct visual pathways in the human cortex.

The Caretaker Obstreperous-Behavior Rating Assessment (COBRA) scale

To evaluate the usefulness and reliability of the Caretaker Obstreperous‐Behavior Rating Assessment (COBRA), a new test instrument for caretaker assessment of types and severity of “obstreperous behaviors” (OBs) in demented patients.

Familial Alzheimer's disease: Site of mutation influences clinical phenotype

Alzheimers disease (AD) is caused by multiple genetic and/or environmental etiologies. Because differences in the genetically determined pathogenesis may cause differences in the phenotype, we examined age at onset and age at death in 90 subjects with dominantly inherited AD due to different mutations (amyloid precursor protein, presenilin‐1, and presenilin‐2 genes). We found that among patients with dominantly inherited AD, genetic factors influence both age at onset and age at death. Ann Neurol 2000;48:376–379

Cognition and Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is classically described as a pure motor disease; however, there is growing evidence of a range of cognitive impairment. Cognitive abnormalities include deficiencies in frontal executive skills, varying from mild deficits to meeting criteria for diagnosis of frontotemporal dementia (FTD). Cognitive impairment occurs in sporadic and familial forms of ALS. Patients may present with cognitive deficits before, after, or at the onset of motor neuron disease. Structural and functional imaging studies have shown extramotor cortical degeneration corresponding to levels of frontal executive impairment on neuropsychologic testing. In addition, ALS and a subset of FTD patients display common pathological findings on immunohistochemistry staining. It is believed that these disorders represent a continuum between motor and nonmotor cortical degeneration. The purpose of this article is to review the literature on cognitive deficits in ALS. Identifying changes in cognition is critical for physicians and caregivers of ALS patients, as cognitive decline may interfere with patient compliance. Diagnosis and treatment of cognitive symptoms in ALS patients may improve quality of life.

Long-term statin therapy and CSF cholesterol levels: implications for Alzheimer's disease.

Background/Aims: It is not yet established whether statins (lipophilic or hydrophilic) reduce the risk of Alzheimer’s disease and, if so, by differentially modifying brain lipid levels. Our aim was to assess changes in brain cholesterol metabolism as reflected in the cerebrospinal fluid (CSF) before and after treatment with either atorvastatin or simvastatin. Methods: We carried out a longitudinal analysis of CSF cholesterol, lathosterol and 24(S)-hydroxycholesterol before and after treatment with maximum doses of statins in 10 asymptomatic subjects, 8 of whom were heterozygous for apolipoprotein E ε4, and in 6 presymptomatic PS1 subjects. Results: Statins initially reduced CSF lathosterol cholesterol and 24(S)-hydroxycholesterol in both PS1 and non-PS1 subjects reaching a nadir at 6–7 months, followed by a return to baseline at 15 months with an overshoot at 2 years, tending to return to baseline thereafter. Conclusions: Possible long-term protective effects of statins are not likely largely related to the temporally-dependent biphasic effects of statin therapy upon the magnitude and direction of changes in CSF lipid levels and their subsequent return to baseline levels.