Associations Between Cancer and Alzheimer\u27s Disease in a U.S. Medicare Population: Case-control and Cohort Studies

Several studies have reported bidirectional inverse associations between cancer and Alzheimer\u27s disease (AD). This study evaluates these relationships in a Medicare population. Using Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data, 1992-2005, we evaluated cancer risks following AD in a case-control study of 836,947 cancer cases and 142,869 controls as well as AD risk after cancer in 742,809 cancer patients and a non-cancer group of 420,518. We applied unconditional logistic regression to estimate odds ratios (ORs) and Cox proportional hazards models to estimate hazards ratios (HRs). We also evaluated cancer in relation to automobile injuries as a negative control to explore potential study biases. In the case-control analysis, cancer cases were less likely to have a prior diagnosis of AD than controls (OR = 0.86; 95% CI = 0.81-0.92). Cancer cases were also less likely than controls to have prior injuries from automobile accidents to the same degree (OR = 0.83; 95% CI = 0.78-0.88). In the prospective cohort, there was a lower risk observed in cancer survivors, HR = 0.87 (95% CI = 0.84-0.90). In contrast, there was no association between cancer diagnosis and subsequent automobile accident injuries (HR = 1.03; 95% CI = 0.98-1.07). That cancer risks were similarly reduced after both AD and automobile injuries suggest biases against detecting cancer in persons with unrelated medical conditions. The modestly lower AD risk in cancer survivors may reflect underdiagnosis of AD in those with a serious illness. This study does not support a relationship between cancer and AD

Meliora: A Conversation with the Provost

Slides from a talk on the topic of "Meliora - Ever Better," by the new University Provost, Ralph W. Kuncl, given October 10, 2007, to the University community

Toxic Myopathies

Toxic myopathies are myopathies induced by drugs or toxins. This chapter discusses the clinical features and morphological, electrophysiological, and metabolic evidence of these myopathies. Our goal is to provide a framework that can be used to better recognize categories of muscle toxins, understand the mechanisms by which they cause muscle damage, identify risk factors which predispose patients to myopathy, and thereby enhance the ability to diagnose these disorders.https://inspire.redlands.edu/oh_chapters/1027/thumbnail.jp

Calbindin-D28K is Increased in the Ventral Horn of Spinal Cord by Neuroprotective Factors For Motor Neurons

Slow glutamate-mediated neuronal degeneration is implicated in the pathophysiology of motor neuron diseases such as amyotrophic lateral sclerosis (ALS). The calcium-binding proteins calbindin-D28K and parvalbumin have been reported to protect neurons against excitotoxic insults. Expression of calbindin-D28K is low in adult human motor neurons, and vulnerable motor neurons additionally may lack parvalbumin. Thus, it has been speculated that the lack of calcium-binding proteins may, in part, be responsible for early degeneration of the population of motor neurons most vulnerable in ALS. Using a rat organotypic spinal cord slice system, we examined whether the most potent neuroprotective factors for motor neurons can increase the expression of calbindin-D28K or parvalbumin proteins in the postnatal spinal cord. After 4 weeks of incubation of spinal cord slices with 1) glial cell line-derived neurotrophic factor (GDNF), 2) neurturin, 3) insulin-like growth factor I (IGF-I), or 4) pigment epithelium-derived factor (PEDF), the number of calbindin-D28K-immunopositive large neurons (\u3e20 μm) in the ventral horn was higher under the first three conditions, but not after PEDF, compared with untreated controls. Under the same conditions, parvalbumin was not upregulated by any neuroprotective factor. The same calbindin increase was true of IGF-I and GDNF in a parallel glutamate toxicity model of motor neuron degeneration. Taken together with our previous reports from the same model, which showed that all these neurotrophic factors can potently protect motor neurons from slow glutamate injury, the data here suggest that upregulation of calbindin-D28K by some of these factors may be one mechanism by which motor neurons can be protected from glutamate-induced, calcium-mediated excitotoxicity

Comment on Intakes of Vitamin C and Carotenoids and Risk of Amyotrophic Lateral Sclerosis: Pooled Results from 5 Cohort Studies

We read with interest the study by Fitzgerald et al,[1] which found an inverse association between amyotrophic lateral sclerosis (ALS) and dietary intake of beta-carotene and lutein in a pooled cohort analysis. The authors also examined vitamin C intake and vitamin C supplement use, but did not discuss the use of carotenoid supplements (neither beta-carotene nor other carotenoids). Nonetheless, some readers may conclude that supplementation with beta-carotene or other carotenoids, which would generally provide higher doses than dietary intake, might offer even greater protection against ALS. We caution against this inference, particularly because of the results of our study on the relationship between ALS and supplemental beta-carotene (and vitamin E) in a randomized clinical trial of Finnish male smokers.[2] This trial was initiated in the 1980s to determine whether supplementation with vitamin E or beta-carotene reduces lung cancer or other cancer incidence. Although it was not an a priori hypothesis of the trial, our study examined the trial results for the effects of these supplements on ALS risk. In our study, beta-carotene supplements were associated with a slightly elevated, although not statistically significant, risk of ALS. Although the finding is not strong evidence of risk, it remains worrisome. Beta-carotene supplements have been associated with an increase in cancer at several sites.[3] We therefore want to emphasize the conclusion of Fitzgerald et al that the inverse association between ALS and beta-carotene and other carotenoids they reported was based only on dietary intake, and not on use of supplements

Vitamin E Serum Levels and Controlled Supplementation and Risk of Amyotrophic Lateral Sclerosis

There are no observational studies or controlled trials of amyotrophic lateral sclerosis (ALS) and circulating α-tocopherol (vitamin E) for prevention of ALS. This study addresses that gap. The study population comprised 29,127 Finnish male smokers, aged 50−69 years, who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which is both a prospective cohort and a randomized, double-blind, placebo-controlled trial of α-tocopherol (50 mg/day) and β-carotene (20 mg/day). Serum α-tocopherol and β-carotene was assayed at baseline (1985 − 1988). Follow-up (median 16.7 years) continued through 2004. ALS cases were identified through the national Hospital Discharge Register with diagnostic verification by hospital records and death certificates. During 407,260 person-years of follow-up, 50 men were identified with ALS. For males with serum α-tocopherol concentration above the median (≥ 11.6 mg/l), the age-adjusted relative risk (RR) compared to α-tocopherol below the median, was 0.56 (95% confidence interval 0.32 − 0.99), p = 0.046. The RR among α-tocopherol supplement recipients was 0.75 (95% CI 0.32 − 1.79), p = 0.52. Neither serum β-carotene level nor β-carotene supplementation was associated with ALS. In conclusion, the results are consistent with a hypothesized protective effect of α-tocopherol on ALS risk. However, pooled analyses of cohorts with serum and controlled trials are needed to clarify the role of α-tocopherol in ALS risk

The Risk of Amyotrophic Lateral Sclerosis After Cancer in U.S. Elderly Adults: A Population-Based Prospective Study

Although epidemiologic studies have examined the risk of amyotrophic lateral sclerosis (ALS) in relation to cancer, none have been large population-based studies using incident ALS and adjusting for medical surveillance. Addressing those limitations, all first primary cancer cases from the Surveillance, Epidemiology and End Results (SEER) Program (1992-2005), linked to Medicare claims data were used. Cases were followed from cancer diagnosis until the earliest date of ALS diagnosis, a break in Medicare claims data, death, age 85 or December 31, 2005. A comparison group from a 5% random Medicare sample in the SEER areas who were cancer-free and censored as above, or until a cancer diagnosis were selected. ALS outcomes were derived from medical claims. The proportional hazards models to estimate ALS hazard ratios (HRs), using age as the time scale, adjusting for sex, race and physician visits, and stratifying the baseline hazard on birth year and SEER registry were used. A total of 303 ALS cases were ascertained in cancer patients (2,154,062 person-years) compared with 246 ALS cases (2,467,634 person-years) in the reference population. There was no overall relationship between cancer and ALS (HR = 0.99; 95% CI = 0.81-1.22), nor by gender or race. Except for an elevated ALS risk in the first year after a leukemia diagnosis, the relationship between site-specific cancers and ALS was null after correcting for multiple comparisons. Having a cancer diagnosis was not associated with an overall risk of incident ALS. The short-term ALS risk after leukemia may reflect screening or reporting errors

Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly

Objective: Statins are commonly prescribed drugs that have been inconsistently associated with amyotrophic lateral sclerosis (ALS) risk. We examined associations between ALS risk and overall statin use, statin categories based on lipophilicity and other cholesterol-lowering medications, in Medicare beneficiaries. Methods: In this nation-wide population-based case-control study, 10,450 Medicare participants (ages 66–89 years) diagnosed with ALS, using Medicare Parts A and B claims, between 1 January 2008 and 31 December 2014, were frequency-matched to 104,500 controls on age, sex, and selection year. Odds ratios (ORs) for the association between statins and ALS were estimated using logistic regression models. Covariates included dyslipidemia, other comorbidities, age, sex, race, proxies for smoking and obesity, Medicare use, and indicators of socioeconomic status. Statin use derived from Medicare Part D claims. Non–statin cholesterol–lowering drugs were evaluated as comparison drugs. Results: ALS risk was reduced with statin use (OR = 0.87 (95% confidence interval (CI) = 0.83–0.91)). While risk was unrelated to three cholesterol-lowering medications (nitrates, bile acid sequestrants, and ezetimibe), it was associated with fibrates (OR = 0.88 (95% CI = 0.80–0.97)). Risk for lipophilic statins was slightly lower than for other statins. ALS risk was lower in all statin categories for dyslipidemic individuals, but only lipophilic statins were associated with lower risk in non-dyslipidemic individuals and demonstrated an inverse trend with duration. Conclusions: Our findings suggest that statins are associated with lower ALS risk and offer new evidence that fibrates may be related to lower risk. However, we were unable to fully adjust for smoking and body mass index