Health status in older hospitalized patients with cancer or non-neoplastic chronic diseases

BACKGROUND: Whether cancer is more disabling than other highly prevalent chronic diseases in the elderly is not well understood, and represents the objective of the present study. METHODS: We used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study, a large collaborative observational study based in community and university hospitals located throughout Italy. Our series consisted of three groups of patients with non-neoplastic chronic disease (congestive heart failure, CHF, N = 832; diabetes mellitus, N = 939; chronic obstructive pulmonary disease, COPD, N = 399), and three groups of patients with cancer (solid tumors without metastasis, N = 813; solid tumors with metastasis, N = 259; leukemia/lymphoma, N = 326). Functional capabilities were ascertained using the activities of daily living (ADL) scale, and categorical variables for dependency in at least 1 ADL or dependency in 3 or more ADLs were considered in the analysis. Cognitive status was evaluated by the 10-items Hodgkinson Abbreviated Mental Test (AMT). RESULTS: Cognitive impairment was more prevalent in patients with CHF (28.0%) or COPD (25.8%) than in those with cancer (solid tumors = 22.9%; leukemia/lymphoma = 19.6%; metastatic cancer = 22.8%). Dependency in at least 1 ADL was highly prevalent in patients with metastatic cancer (31.3% vs. 24% for patients with CHF and 22.4% for those with non-metastatic solid tumors, p < 0.001). In people aged 80 years or more, metastatic cancer was not associated with increased prevalence of physical disability. In multivariable analysis, metastatic cancer was associated with a greater prevalence of physical (OR 2.09, 95%CI 1.51–2.90) but not cognitive impairment (OR 1.34, 95%CI 0.94–1.91) with respect to CHF patients. Finally, diabetes was significantly associated with cognitive impairment (OR 1.40, 95%CI 1.11–1.78). CONCLUSION: Cancer should not be considered as an ineluctable cause of severe cognitive and physical impairment, at least not more than other chronic conditions highly prevalent in older people, such as CHF and diabetes mellitus

Covariation of depressive symptoms, parkinsonism, and post-dexamethasone plasma cortisol levels in a bipolar patient: simultaneous response to ECT and lithium carbonate

: A patient presented with concurrent mood congruent delusions, parkinsonism, and elevated post-dexamethasone plasma cortisol levels. This triad could result from simultaneous development of cholinergic-monoaminergic dysfunction within critical limbic and extrapyramidal loci. The magnitude of each abnormality decreased in concert during a course of electroconvulsive therapy (ECT). Remaining abnormalities disappeared during treatment with lithium. Actions of ECT and lithium on muscarinic systems are reviewed, and a strategy for testing the hypothesis that dysfunction of cholinergic-monoaminergic mechanisms develops in parallel in different neural networks is considered.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66202/1/j.1600-0447.1986.tb06229.x.pd

A genome-wide association study for late-onset Alzheimer's disease using DNA pooling

Background: Late-onset Alzheimer's disease (LOAD) is an age related neurodegenerative disease with a high prevalence that places major demands on healthcare resources in societies with increasingly aged populations. The only extensively replicable genetic risk factor for LOAD is the apolipoprotein E gene. In order to identify additional genetic risk loci we have conducted a genome-wide association (GWA) study in a large LOAD case – control sample, reducing costs through the use of DNA pooling. Methods: DNA samples were collected from 1,082 individuals with LOAD and 1,239 control subjects. Age at onset ranged from 60 to 95 and Controls were matched for age (mean = 76.53 years, SD = 33), gender and ethnicity. Equimolar amounts of each DNA sample were added to either a case or control pool. The pools were genotyped using Illumina HumanHap300 and Illumina Sentrix HumanHap240S arrays testing 561,494 SNPs. 114 of our best hit SNPs from the pooling data were identified and then individually genotyped in the case – control sample used to construct the pools. Results: Highly significant association with LOAD was observed at the APOE locus confirming the validity of the pooled genotyping approach. For 109 SNPs outside the APOE locus, we obtained uncorrected p-values ≤ 0.05 for 74 after individual genotyping. To further test these associations, we added control data from 1400 subjects from the 1958 Birth Cohort with the evidence for association increasing to 3.4 × 10-6 for our strongest finding, rs727153. rs727153 lies 13 kb from the start of transcription of lecithin retinol acyltransferase (phosphatidylcholine – retinol O-acyltransferase, LRAT). Five of seven tag SNPs chosen to cover LRAT showed significant association with LOAD with a SNP in intron 2 of LRAT, showing greatest evidence of association (rs201825, p-value = 6.1 × 10-7). Conclusion: We have validated the pooling method for GWA studies by both identifying the APOE locus and by observing a strong enrichment for significantly associated SNPs. We provide evidence for LRAT as a novel candidate gene for LOAD. LRAT plays a prominent role in the Vitamin A cascade, a system that has been previously implicated in LOAD

Birth weight and cognitive performance in older women: the Rancho Bernardo study

Low birth weight is associated with poorer cognitive function from infancy through early adulthood, but little is known about low birth weight and cognitive performance in the elderly. This study examines the association of birth weight with cognitive function in community-dwelling older women. Participants were 292 community-dwelling women aged 55–89 (median = 71 years) who attended a 1988–91 clinic visit when cognitive function was assessed, and responded to a 1991 mailed questionnaire assessing birth weight. All analyses were adjusted for age and education. Birth weight ranged from 2 to 12 pounds (lbs; mean = 7.4 ± 1.9). When birth weight was categorized into tertiles (2–6.9 lbs, 7–8 lbs, and 8.1–12.4 lbs), women in the lowest tertile had significantly lower (“poorer”) scores on Serial 7’s, a test of concentration and calculation (p < 0.05). Other birth weight categorizations (lowest quartile or quintile, or birth weight <5.5 lbs vs. 5.6–8.9 lbs and ≥9 lbs) did not improve the prediction of poor performance on Serial 7’s. Birth weight as a continuous variable was significantly and positively associated with Serial 7’s test scores (p = 0.04). Results suggest that small decrements in cognitive function tasks involving calculation may persist throughout life in women who were of relatively low birth weight. Although this association could be spurious, it deserves further evaluation

Prediction of Dementia in Primary Care Patients

BACKGROUND: Current approaches for AD prediction are based on biomarkers, which are however of restricted availability in primary care. AD prediction tools for primary care are therefore needed. We present a prediction score based on information that can be obtained in the primary care setting. METHODOLOGY/PRINCIPAL FINDINGS: We performed a longitudinal cohort study in 3.055 non-demented individuals above 75 years recruited via primary care chart registries (Study on Aging, Cognition and Dementia, AgeCoDe). After the baseline investigation we performed three follow-up investigations at 18 months intervals with incident dementia as the primary outcome. The best set of predictors was extracted from the baseline variables in one randomly selected half of the sample. This set included age, subjective memory impairment, performance on delayed verbal recall and verbal fluency, on the Mini-Mental-State-Examination, and on an instrumental activities of daily living scale. These variables were aggregated to a prediction score, which achieved a prediction accuracy of 0.84 for AD. The score was applied to the second half of the sample (test cohort). Here, the prediction accuracy was 0.79. With a cut-off of at least 80% sensitivity in the first cohort, 79.6% sensitivity, 66.4% specificity, 14.7% positive predictive value (PPV) and 97.8% negative predictive value of (NPV) for AD were achieved in the test cohort. At a cut-off for a high risk population (5% of individuals with the highest risk score in the first cohort) the PPV for AD was 39.1% (52% for any dementia) in the test cohort. CONCLUSIONS: The prediction score has useful prediction accuracy. It can define individuals (1) sensitively for low cost-low risk interventions, or (2) more specific and with increased PPV for measures of prevention with greater costs or risks. As it is independent of technical aids, it may be used within large scale prevention programs

A fibril-specific, conformation-dependent antibody recognizes a subset of Aβ plaques in Alzheimer disease, Down syndrome and Tg2576 transgenic mouse brain

Beta-amyloid (Aβ) is thought to be a key contributor to the pathogenesis of Alzheimer disease (AD) in the general population and in adults with Down syndrome (DS). Different assembly states of Aβ have been identified that may be neurotoxic. Aβ oligomers can assemble into soluble prefibrillar oligomers, soluble fibrillar oligomers and insoluble fibrils. Using a novel antibody, OC, recognizing fibrils and soluble fibrillar oligomers, we characterized fibrillar Aβ deposits in AD and DS cases. We further compared human specimens to those obtained from the Tg2576 mouse model of AD. Our results show that accumulation of fibrillar immunoreactivity is significantly increased in AD relative to nondemented aged subjects and those with select cognitive impairments (p < 0.0001). Further, there was a significant correlation between the extent of frontal cortex fibrillar deposit accumulation and dementia severity (MMSE r = −0.72). In DS, we observe an early age of onset and age-dependent accumulation of fibrillar OC immunoreactivity with little pathology in similarly aged non-DS individuals. Tg2576 mice show fibrillar accumulation that can be detected as young as 6 months. Interestingly, fibril-specific immunoreactivity was observed in diffuse, thioflavine S-negative Aβ deposits in addition to more mature neuritic plaques. These results suggest that fibrillar deposits are associated with disease in both AD and in adults with DS and their distribution within early Aβ pathology associated with diffuse plaques and correlation with MMSE suggest that these deposits may not be as benign as previously thought

Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease

status: publishe

Study protocol for the recreational stimulation for elders as a vehicle to resolve delirium superimposed on dementia (Reserve For DSD) trial

<p>Abstract</p> <p>Background</p> <p>Delirium is a state of confusion characterized by an acute and fluctuating decline in cognitive functioning. Delirium is common and deadly in older adults with dementia, and is often referred to as delirium superimposed on dementia, or DSD. Interventions that treat DSD are not well-developed because the mechanisms involved in its etiology are not completely understood. We have developed a theory-based intervention for DSD that is derived from the literature on cognitive reserve and based on our prior interdisciplinary work on delirium, recreational activities, and cognitive stimulation in people with dementia. Our preliminary work indicate that use of simple, cognitively stimulating activities may help resolve delirium by helping to focus inattention, the primary neuropsychological deficit in delirium. Our primary aim in this trial is to test the efficacy of Recreational Stimulation for Elders as a Vehicle to resolve DSD (RESERVE- DSD).</p> <p>Methods/Design</p> <p>This randomized repeated measures clinical trial will involve participants being recruited and enrolled at the time of admission to post acute care. We will randomize 256 subjects to intervention (RESERVE-DSD) or control (usual care). Intervention subjects will receive 30-minute sessions of tailored cognitively stimulating recreational activities for up to 30 days. We hypothesize that subjects who receive RESERVE-DSD will have: decreased severity and duration of delirium; greater gains in attention, orientation, memory, abstract thinking, and executive functioning; and greater gains in physical function compared to subjects with DSD who receive usual care. We will also evaluate potential moderators of intervention efficacy (lifetime of complex mental activities and APOE status). Our secondary aim is to describe the costs associated with RESERVE-DSD.</p> <p>Discussion</p> <p>Our theory-based intervention, which uses simple, inexpensive recreational activities for delivering cognitive stimulation, is innovative because, to our knowledge it has not been tested as a treatment for DSD. This novel intervention for DSD builds on our prior delirium, recreational activity and cognitive stimulation research, and draws support from cognitive reserve theory.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267682">NCT01267682</a></p