A Survey of Knowledge and Views Concerning Genetic and Amyloid PET Status Disclosure.

INTRODUCTION: This survey characterizes viewpoints of cognitively intact at-risk participants in an Alzheimer prevention registry if given the opportunity to learn their genetic and amyloid PET status. METHODS: 207 participants were offered a 25-item survey. They were asked if they wished to know their ApoE and amyloid PET status, and if so, reasons for wanting to know, or not, and the effects of such information on life plans. RESULTS: 164 (79.2%) of registrants completed the survey. Among those who were unaware of their ApoE or amyloid PET results, 80% desired to know this information. The most common reasons for wanting disclosure were to participate in research, to arrange personal affairs, to prepare family for illness, and to move life plans closer into the future. When asked if disclosure would help with making plans to end one's life when starting to lose their memory, 12.7% vs. 11.5% responded yes for ApoE and amyloid PET disclosures, respectively. Disclosure of these test results, if required for participation in a clinical trial, would make 15% of people less likely to participate. Likelihood of participation in prevention research and the desire to know test results were not related to scores on brief tests of knowledge about the tests. DISCUSSION: These results suggest that stakeholders in AD prevention research generally wish to know biological test information about their risk for developing AD to assist in making life plans.

A longitudinal study of drivers with Alzheimer disease.

OBJECTIVE: The goal of this study was to define the natural progression of driving impairment in persons who initially have very mild to mild dementia. METHODS: We studied 128 older drivers, including 84 with early Alzheimer disease (AD) and 44 age-matched control subjects without cognitive impairment. Subjects underwent repeated assessments of their cognitive, neurologic, visual, and physical function over 3 years. Self-reports of driving accidents and traffic violations were supplemented by reports from family informants and state records. Within 2 weeks of the office evaluation, subjects were examined by a professional driving instructor on a standardized road test. RESULTS: At baseline, subjects with AD had experienced more accidents and performed more poorly on the road test, compared to controls. Over time, both groups declined in driving performance on the road test, with subjects with AD declining more than controls. Survival analysis indicated that while the majority of subjects with AD passed the examination at baseline, greater severity of dementia, increased age, and lower education were associated with higher rates of failure and marginal performance. CONCLUSIONS: This study confirms previous reports of potentially hazardous driving in persons with early Alzheimer disease, but also indicates that some individuals with very mild dementia can continue to drive safely for extended periods of time. Regular follow-up assessments, however, are warranted in those individuals.

Visual and cognitive predictors of driving safety in Parkinson's disease patients.

This study assessed the clinical utility of contrast sensitivity (CS) relative to attention, executive function, and visuospatial abilities for predicting driving safety in participants with Parkinson's disease (PD). Twenty-five, non-demented PD patients completed measures of contrast sensitivity, visuospatial skills, executive functions, and attention. All PD participants also underwent a formal on-road driving evaluation. Of the 25 participants, 11 received a marginal or unsafe rating on the road test. Poorer driving performance was associated with worse performance on measures of CS, visuospatial constructions, set shifting, and attention. While impaired driving was associated with a range of cognitive and visual abilities, only a composite measure of executive functioning and visuospatial abilities, and not CS or attentional skills, predicted driving performance. These findings suggest that neuropsychological tests, which are multifactorial in nature and require visual perception and visual spatial judgments are the most useful screening measures for hazardous driving in PD patients.

Excessive daytime sleepiness and on-road driving performance in patients with Parkinson's disease.

The impact of excessive daytime sleepiness (EDS) on road test performance was examined in patients with Parkinson's disease (PD). Twenty-one patients with PD completed the Epworth Sleepiness Scale (ESS) and an on-road driving test. Five participants had EDS according to their self-report on the ESS. Neither EDS nor PD medications were associated with on-road driving performance. These findings suggest that in this pilot study EDS did not impair PD patients' driving skills on a formal driving evaluation.

Single photon emission computed tomography, magnetic resonance imaging hyperintensity, and cognitive impairments in patients with vascular dementia.

BACKGROUND: The relationship between subcortical hyperintensity (SH) on magnetic resonance imaging (MRI), cortical perfusion on single photon emission computed tomography (SPECT), and cognitive function is not well understood. The authors examined these relationships in individuals with vascular dementia (VaD), paying particular attention to frontal lobe function to determine whether the presence of SH on MRI was associated with frontal hypoperfusion on SPECT, which in turn would be associated with impairments of executive-attention function. METHODS: Patients with vascular dementia (n = 26) were assessed on neurocognitive tests and brain MRI and SPECT. SH volume was quantified from the axial T2-weighted fluid attenuated inversion recovery MRI. Total counts of activation across voxels for 12 cortical regions of interest were determined from SPECT. Perfusion ratios of both total cortical and frontal activation relative to cerebellum activation were derived, and regression analyses were performed to determine the relationships between cognitive, MRI, and SPECT indices. RESULTS: SH volume on MRI was significantly associated with frontal lobe perfusion, but not with global cortical perfusion as measured by SPECT. Frontal lobe perfusion did not consistently correlate with performance on measures of executive-attention function, although both total and frontal perfusion ratios were significantly associated with other cognitive functions. CONCLUSIONS: These results suggest that a functional "disconnection" between the frontal lobes and subcortical structures does not fully account for the magnitude of global cognitive impairment in VaD. Cortical perfusion as measured by SPECT appears to be associated with cognitive performance, but not specifically executive-attention dysfunction. Additional studies are needed to further examine the relationship between subcortical and cortical function in VaD.

Executive function and magnetic resonance imaging subcortical hyperintensities in vascular dementia.

OBJECTIVE: To determine the relation between subcortical hyperintensities (SHs) visible on magnetic resonance imaging and executive function among patients with vascular dementia. BACKGROUND: The relation between SHs and executive dysfunction is not well understood, because studies have varied widely in methodology and have produced conflicting results. METHOD: We examined the relation between SHs (expressed as a percentage of total brain volume, not including ventricular volume) and six tests of executive function in a well-defined group of 24 individuals with vascular dementia. Executive tests were divided in two groups: Attention/Speed and Abstraction/Problem Solving. Bivariate correlations were computed between individual neuropsychological variables and SHs. RESULTS: Results showed significant bivariate correlations between SHs and three of the four tests in the Attention/Speed domain. Subcortical hyperintensities shared virtually no association with performance on tests in the Abstraction/Problem-Solving domain. CONCLUSIONS: The finding that SHs are significantly associated with psychomotor slowing and attentional dysfunction is consistent with what is known about the behavioral manifestations of subcortical disease. More detailed investigations of the regional distribution of SHs as well as measures of atrophy, hypoperfusion, and hypometabolism may be necessary to accurately characterize the complex relation between vascular disease and different aspects of executive dysfunction.

Performance on the Mattis Dementia Rating Scale in patients with vascular dementia: relationships to neuroimaging findings.

Impairment on screening measures such as the Mattis Dementia Rating Scale (MDRS) provides evidence of dementia in patients with cerebrovascular disease. However, the relationships between neuroimaging findings and performance on the MDRS in vascular dementia (VD) have not been determined. In the present study, we examined the relationships between subcortical hyperintensity (SH) volume and whole brain volume (WBV) on the subscales and total score of the MDRS. Results revealed that SH accounted for a significant amount of variance on the Initiation/Perseveration and Construction subscales, whereas WBV accounted for a significant amount of variance on the Memory subscale. The total score on the MDRS was found to be significantly related to WBV but not SH. These results suggest that subcortical damage and brain volume account for different aspects of cognitive decline in VD and that overall cognitive impairment may reflect cortical and subcortical involvement.

Gender differences in the frequency and treatment of behavior problems in Parkinson's disease. SAGE Study Group. Systematic Assessment and Geriatric drug use via Epidemiology.

OBJECTIVE: To determine gender differences in the prevalence, survival rates, and management of noncognitive behavioral problems of patients with Parkinson's disease (PD) in nursing homes (NH). METHODS: We performed an observational study on 24,402 residents with PD using the Systematic Assessment and Geriatric drug use via Epidemiology (SAGE) database collected from the Minimum Data Set on a cross-section of over 400,000 NH residents in five US states. Gender differences in behavior were used to predict differences in pharmacologic and nonpharmacologic therapies using logistic regression. Similar analyses were done to evaluate gender differences in 1-year survival rates among patients with PD with and without behavioral problems. RESULTS: 36% of men and 33% of women exhibited behavioral problems. Wandering, verbal and physical abusiveness, and inappropriate behavior tended to be more common in men, especially among PD residents with severe cognitive impairment. Hallucinations and delusions were equally prevalent between genders and depressive symptoms were more common in women. Regardless of behavioral manifestation, men were more likely to receive antipsychotic drugs, whereas women were more likely to receive antidepressants. This gender difference in treatment was also widest among the severely demented group. Although women lived longer, no difference in survival curves were noted between PD residents with and without behavioral problems. CONCLUSION: Gender appears to play an important role in determining the frequency and treatment of behavioral problems of NH residents with PD.

A single-photon emission computed tomography imaging study of driving impairment in patients with Alzheimer's disease.

Single-photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination (MMSE). Driving impairment in Alzheimer's disease is related to changes in cortical function which vary according to the severity of the disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the MMSE that are weighted toward left-hemisphere-based verbal tasks.

Gender differences in the treatment of behavior problems in Alzheimer's disease. SAGE Study Group. Systemic Assessment of Geriatric drug use via Epidemiology.

OBJECTIVE: To define gender differences in noncognitive behavioral problems of patients with AD and differences in the associated treatment of those problems. DESIGN/METHODS: We performed an observational study using the Systematic Assessment and Geriatric drug use via Epidemiology (SAGE) database, which contains data collected with the Minimum Data Set on a cross-section of nursing home residents in five US states. Behavior problems were documented at the first assessment of 28,367 residents with AD. We evaluated the role of gender differences in behavior as predictors of differences in nonpharmacologic versus specific pharmacologic therapies with psychoactive medications using logistic regression. RESULTS: Men were more likely than women to exhibit behavior problems such as wandering, abusiveness, and social impropriety (59% versus 50% for any behavior problem). Hallucinations and delusions as well as depression were equally prevalent in men and women. Nevertheless, men were more likely to receive psychoactive medications. Among the specific drug categories examined, and controlling for age and degree of cognitive impairment, men were more likely to receive antipsychotic drugs and less likely to be receiving antidepressants. CONCLUSION: Gender appears to play an important role in determining the frequency of behavioral problems in nursing home residents with AD, which may influence choice of treatments as well as the decision whether to treat. The use of more potent tranquilizers in men with problem behaviors has potential implications for morbidity, deserving further investigation.

Lateralized cortical perfusion in women with Alzheimer's disease.

OBJECTIVE: To define the pathophysiologic substrate of gender differences in cognition and behavior in Alzheimer's disease (AD). DESIGN: Hemispheric regional cerebral blood flow (rCBF) was studied in a consecutive series of dementia patients using single photon emission computed tomography (SPECT). PARTICIPANTS: Subjects included 300 outpatients who were studied with SPECT as part of a diagnostic evaluation for degenerative dementia or memory disorder. METHOD: Based on qualitative descriptions by a radiologist, subjects were classified as having unilateral left, unilateral right, bilateral, or no perfusion defects. Semiquantitative analysis of SPECT images was also performed using region of interest radionuclide counts normalized to the cerebellum. RESULTS: Among 174 females and 126 males, unilateral left hemisphere defects were found more commonly in women than men (24% vs 10%; chi 2 = 9.4; P = .009). This observation was most significant for the 103 females and 62 males regarded as having probable AD (26% vs 8%; chi 2 = 9.3; P = .01). In a multiple regression model of clinical variables, shorter duration of disease and female gender were significant independent predictors of the unilateral left hemisphere pattern among those with probable AD. Age, family history, education, handedness, and severity of cognitive impairment were not significant contributors. CONCLUSIONS: Women with AD exhibit greater heterogeneity in rCBF than men. Asymmetry in rCBF occurs more often in women. In some cases, this is related to relative preservation of right hemisphere function in women.

Cognition and behavior in patients with Alzheimer's disease.

Clinically relevant differences in cognition and behavior exist between men and women with Alzheimer's disease. Underlying these differences are variations in the topographic brain changes caused by pathologic processes, as well as differences in hormonal brain physiology and genetic influences. Our understanding of how these gender differences affect the clinical expression of Alzheimer's disease is in its infancy. Research in this area will likely yield further insights into potential therapies directed toward symptomatic and preventive interventions.

Complementary and alternative medicines for Alzheimer's disease.

The recent successes of large, multicenter clinical trials of acetylcholinesterase inhibitors for symptomatic treatment of Alzheimer's disease have spawned enthusiasm that this common and fatal neurologic disease is "treatable." A parallel explosion has occurred in the consumption of alternative medicines by the public seeking more effective, natural, or safer methods for treatment of dementia. Some of these medicines may, in fact, be biologically active in modulating the disease as well as producing side effects and interactions with accepted pharmaceuticals. This review brings to focus the scientific evidence presently available regarding such agents.

A SPECT imaging study of MRI white matter hyperintensity in patients with degenerative dementia.

We investigated the correlation between cortical perfusion and white matter hyperintensities on magnetic resonance images (MRI) of patients with dementia. The study included 40 subjects, each of whom had undergone both MRI and single-photon emission computed tomography (SPECT) studies as part of their diagnostic evaluation for degenerative dementia. Two neuroradiologists rated the MRI films for severity of periventricular white matter changes on a 0-5 point scale and severity of subcortical white matter changes on a 0-4 point scale. Twelve regions of interest from association cortex were sampled for the semiquantitative analysis of SPECT images. No relationship was found between these global MRI ratings and semiquantitative or qualitative SPECT findings. Dementia severity as measured by the Mini-Mental State Examination and the Clinical Dementia Rating was significantly correlated with SPECT, whereas age was significantly correlated with MRI ratings, particularly in the periventricular regions. These data support the view that cortical SPECT abnormalities are not associated with global MRI abnormalities in the subcortical and periventricular regions of patients with a clinical picture of degenerative dementia.