Faculty Bibliography

BACKGROUND: The longitudinal cognitive course in Parkinson's disease (PD) with and without dementia remains undefined. We compared cross-sectional models of cognition in PD (both with and without dementia), Alzheimer's disease (AD), and nondemented aging and followed the participants over time. METHOD: Previously validated models of cognitive performance in AD and nondemented aging were extended to individuals with PD (with dementia, n = 71; without dementia, n = 47). Confirmatory factor analysis and piecewise regression were used to compare the longitudinal course of participants with PD with 191 cognitively healthy subjects and 115 individuals with autopsy-confirmed AD. RESULTS: A factor analytic model with one general factor and three specific factors (verbal memory, visuospatial memory, working memory) fit demented and nondemented PD. Longitudinal change indicated that individuals with PD with dementia declined significantly more rapidly on visuospatial and verbal memory tasks than AD alone. Cognitive declines across all factors in AD and PD dementia accelerated several years prior to clinical dementia diagnosis. CONCLUSION: Both specific and global cognitive changes are witnessed in PD and AD. Longitudinal profiles of cognitive decline in PD and AD differed. PD with or without dementia has a core feature of longitudinal decline in visuospatial abilities

Dementia is a global public health problem and detection in the primary care setting, particularly in developing countries, is challenging. The aim of this research was to produce the cross-cultural validation of the AD8 interview to the Brazilian Portuguese Language. The original version of the AD8 was submitted to translation, back-translation, and application of the questionnaire to 20 elderly informants for face validation. The AD8-Brazil was then evaluated in 109 community-dwelling elderly with a sociodemographic questionnaire, clinical examination, Mini Mental State Examination (MMSE), Katz Inventory of Activities of Daily Living (ADL), and Clinical Dementia Rating scale (CDR). The AD8-Brazil was compared with the other instruments and with the clinical diagnosis (DSM-IV) for criterion validation. There was significant agreement of AD8-Brazil with diagnosis of dementia (p < 0.001), MMSE (p = 0.047), and ADL (PFisher = 0.004). Also, the AD8-Brazil was able to differentiate the stages of dementia by CDR scale. The reliability was high (alpha = 0.818) and reproducibility analysis showed excellent inter-rater (kappa = 0.889) and test-retest consistency (kappa = 0.814). The AD8-Brazil showed excellent discrimination between CDR 0 and CDR > 0 (area under the curve 86.1%) and between CDR 0 and CDR 0.5 (area under the curve 76.9%). The administration of the questionnaire took 2.3 +/- 0.1 minutes. The Brazilian version of the AD8 is a valid, reliable, quick, and easy screening instrument for dementia

BACKGROUND: The etiology of Parkinson disease (PD) has yet to be fully elucidated. We examined the consequences of injections of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a toxic metabolite of dopamine, into the substantia nigra of rats on motor behavior and neuronal survival. METHODS/PRINCIPAL FINDINGS: A total of 800 nl/rat of DOPAL (1 microg/200 nl) was injected stereotaxically into the substantia nigra over three sites while control animals received similar injections of phosphate buffered saline. Rotational behavior of these rats was analyzed, optical density of striatal tyrosine hydroxylase was calculated, and unbiased stereological counts of the substantia nigra were made. The rats showed significant rotational asymmetry ipsilateral to the lesion, supporting disruption of dopaminergic nigrostriatal projections. Such disruption was verified since the density of striatal tyrosine hydroxylase decreased significantly (p<0.001) on the side ipsilateral to the DOPAL injections when compared to the non-injected side. Stereological counts of neurons stained for Nissl in pars compacta of the substantia nigra significantly decreased (p<0.001) from control values, while counts of those in pars reticulata were unchanged after DOPAL injections. Counts of neurons immunostained for tyrosine hydroxylase also showed a significant (p=0.032) loss of dopaminergic neurons. In spite of significant loss of dopaminergic neurons, DOPAL injections did not induce significant glial reaction in the substantia nigra. CONCLUSIONS: The present study provides the first in vivo quantification of substantia nigra pars compacta neuronal loss after injection of the endogenous toxin DOPAL. The results demonstrate that injections of DOPAL selectively kills SN DA neurons, suggests loss of striatal DA terminals, spares non-dopaminergic neurons of the pars reticulata, and triggers a behavioral phenotype (rotational asymmetry) consistent with other PD animal models. This study supports the 'catecholaldehyde hypothesis' as an important link for the etiology of sporadic PD

CONTEXT: Docosahexaenoic acid (DHA) is the most abundant long-chain polyunsaturated fatty acid in the brain. Epidemiological studies suggest that consumption of DHA is associated with a reduced incidence of Alzheimer disease. Animal studies demonstrate that oral intake of DHA reduces Alzheimer-like brain pathology. OBJECTIVE: To determine if supplementation with DHA slows cognitive and functional decline in individuals with Alzheimer disease. DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled trial of DHA supplementation in individuals with mild to moderate Alzheimer disease (Mini-Mental State Examination scores, 14-26) was conducted between November 2007 and May 2009 at 51 US clinical research sites of the Alzheimer's Disease Cooperative Study. INTERVENTION: Participants were randomly assigned to algal DHA at a dose of 2 g/d or to identical placebo (60% were assigned to DHA and 40% were assigned to placebo). Duration of treatment was 18 months. MAIN OUTCOME MEASURES: Change in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) and change in the Clinical Dementia Rating (CDR) sum of boxes. Rate of brain atrophy was also determined by volumetric magnetic resonance imaging in a subsample of participants (n = 102). RESULTS: A total of 402 individuals were randomized and a total of 295 participants completed the trial while taking study medication (DHA: 171; placebo: 124). Supplementation with DHA had no beneficial effect on rate of change on ADAS-cog score, which increased by a mean of 7.98 points (95% confidence interval [CI], 6.51-9.45 points) for the DHA group during 18 months vs 8.27 points (95% CI, 6.72-9.82 points) for the placebo group (linear mixed-effects model: P = .41). The CDR sum of boxes score increased by 2.87 points (95% CI, 2.44-3.30 points) for the DHA group during 18 months compared with 2.93 points (95% CI, 2.44-3.42 points) for the placebo group (linear mixed-effects model: P = .68). In the subpopulation of participants (DHA: 53; placebo: 49), the rate of brain atrophy was not affected by treatment with DHA. Individuals in the DHA group had a mean decline in total brain volume of 24.7 cm(3) (95% CI, 21.4-28.0 cm(3)) during 18 months and a 1.32% (95% CI, 1.14%-1.50%) volume decline per year compared with 24.0 cm(3) (95% CI, 20-28 cm(3)) for the placebo group during 18 months and a 1.29% (95% CI, 1.07%-1.51%) volume decline per year (P = .79). CONCLUSION: Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00440050

Screening tests for Alzheimer's disease lack sensitivity and specificity. We developed the AD8, a brief dementia screening interview validated against clinical and cognitive evaluations, as an improvement over current screening methods. Because insufficient follow-up has occurred to validate the AD8 against the neuropathologic findings of Alzheimer's disease, we investigated whether AD8 scores correspond to impairment in episodic memory testing and changes in biomarkers of Alzheimer's disease (cerebrospinal fluid and amyloid imaging with Pittsburgh compound B) characteristic of symptomatic Alzheimer's disease. We also compared informant-based assessments with brief performance-based dementia screening measurements such as the Mini Mental State Exam. The sample (n = 257) had a mean age of 75.4 years with 15.1 years of education; 88.7% were Caucasian and 45.5% were male. The sample was divided into two groups based on their AD8 scores: those with a negative dementia screening test (AD8 score 0 or 1, n = 137) and those with a positive dementia screening test (AD8 score >/=2, n = 120). Individuals with positive AD8 scores had abnormal Pittsburgh compound B binding (P < 0.001) and cerebrospinal fluid biomarkers (P < 0.001) compared with individuals with negative AD8 scores. Individuals with positive AD8 tests and positive biomarkers scored in the impaired range on the Wechsler Logical Memory Story A (mean score 7.0 +/- 4.5 for Pittsburgh compound B; mean score 7.6 +/- 5.3 for cerebrospinal fluid amyloid beta protein 1-42). The AD8 area under the curve for Pittsburgh compound B was 0.737 (95% confidence interval: 0.64-0.83) and for cerebrospinal fluid amyloid beta protein 1-42 was 0.685 (95% confidence interval: 0.60-0.77) suggesting good discrimination. The AD8 had superior sensitivity in detecting early stages of dementia compared with the Mini Mental State Examination. The AD8 had a likelihood ratio of a positive test of 5.8 (95% confidence interval: 5.4-6.3) and likelihood ratio of a negative test of 0.04 (95% confidence interval: 0.03-0.06), increasing the pre-test probability of an individual having symptomatic Alzheimer's disease. Individuals with AD8 scores of >/=2 had a biomarker phenotype consistent with Alzheimer's disease and lower performance on episodic memory tests, supporting a diagnosis of Alzheimer's disease. Informant-based assessments may be superior to performance-based screening measures such as the Mini Mental State Examination in corresponding to underlying Alzheimer's disease pathology, particularly at the earliest stages of decline. The use of a brief test such as the AD8 may improve strategies for detecting dementia in community settings where biomarkers may not be readily available, and may enrich clinical trial recruitment by increasing the likelihood that participants have underlying biomarker abnormalities

BACKGROUND: Approximately 3.2 million hospital stays annually involve a person with dementia, leading to higher costs, longer lengths of stay, and poorer outcomes. Older adults with dementia are vulnerable when hospitals are unable to meet their special needs. METHODS: We developed, implemented, and evaluated a training program for 540 individuals at 4 community hospitals. Pretest, posttest, and a 120-day delayed posttest were performed to assess knowledge, confidence, and practice parameters. RESULTS: The mean age of the sample was 46 years; 83% were White, 90% were female, and 60% were nurses. Upon completion, there were significant gains (P's <0.001) in knowledge and confidence in recognizing, assessing, and managing dementia. Attendees reported gains in communication skills and strategies to improve the hospital environment, patient safety, and behavioral management. At 120 days, 3 of 4 hospitals demonstrated maintenance of confidence. In the hospital that demonstrated lower knowledge and confidence scores, the sample was older and had more nurses and more years in practice. CONCLUSIONS: We demonstrate the feasibility of training hospital staff about dementia and its impact on patient outcomes. At baseline, there was low knowledge and confidence in the ability to care for dementia patients. Training had an immediate impact on knowledge, confidence, and attitudes with lasting impact in 3 of 4 hospitals. We identified targets for intervention and the need for ongoing training and administrative reinforcement to sustain behavioral change. Community resources, such as local chapters of the Alzheimer Association, may be key community partners in improving care outcomes for hospitalized persons with dementia

BACKGROUND: Lewy body dementia (LBD) is the second most common cause of dementia, however, little is known about how the clinical diagnosis of LBD is obtained in the community or the caregiver experience while seeking the diagnosis. METHODS: The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers over a 6-month period. RESULTS: The mean age of respondents was 55.9y; 88% were female and 64% had daily contact with patients. The mean age of LBD patients was 75.4y; 62% were male and 46% lived with a caregiver. The most common presentation of symptoms as reported by LBD caregivers was cognitive (48%), motor (39%) or both (13%). The first diagnoses given to the patients were Parkinson disease or other movement disorder (39%), Alzheimer disease or other cognitive disorder (36%), or mental illness (24%). Fifty percent of patients saw >3 doctors for more than 10 visits over the course of 1 year before an LBD diagnosis was established. Neurologists diagnosed most cases (62%), while primary care providers diagnosed only 6% of cases. No differences were found between the presentation of disease and the number of physicians, number of office visits, length of time to establish diagnosis, or type of doctor who finally made an LBD diagnosis. Caregivers viewed physicians as knowledgeable about disease manifestations and treatment options, but not about disease course/prognosis and available community resources and referrals. CONCLUSIONS: These data highlight a need for increasing physician awareness and knowledge of LBD, which will facilitate accurate diagnosis and treatment. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers

Lewy body dementia (LBD) is a common cause of dementia but to date, little is known about caregiver burden. The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers (mean age 56 y; 88% women). The most common initial symptoms were cognitive (48%), motor (39%), or both (13%). Caregivers expressed concerns about fear of future (77%), feeling stressed (54%), loss of social life (52%), and uncertainty about what to do next (50%). Caregivers reported moderate-to-severe burden; 80% felt the people around them did not understand their burden and 54% reported feelings of isolation with spousal caregivers reporting more burden than nonspousal caregivers. Only 29% hired in-home assistance, whereas less than 40% used respite or adult day care, geriatric case managers, or attended a support group meeting. Lack of service utilization occurred despite two-thirds of caregivers reporting medical crises requiring emergency services, psychiatric care, or law enforcement. Caregivers reported preferences for web-based information, directories of LBD expert providers, information on LBD research, and location of local support groups. These findings highlight significant unmet needs for LBD caregivers and provide targets for intervention to reduce caregiver burden. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers