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Background: It is controversial whether B12 deficiency causes dementia or B12 treatment can prevent dementia., Objective: To assess associations between low plasma (P-)B12 levels, B12 treatment, and risk of Alzheimer's disease (AD; primary outcome) and all-cause or vascular dementia (secondary outcomes)., Methods: We conducted a population-based cohort study using Danish registry data to assess associations between low P-B12 levels, high-dose injection or oral B12 treatment, and risk of dementia (study period 2000-2013). The primary P-B12 cohort included patients with a first-time P-B12 measurement whose subsequent B12 treatment was recorded. The secondary B12 treatment cohort included patients with a first-time B12 prescription and P-B12 measurement within one year before this prescription. For both cohorts, patients with low P-B12 levels (<200 pmol/L) were propensity score-matched 1:1 with patients with normal levels (200-600 pmol/L). We used multivariable Cox regression to compute 0-15-year hazard ratios for dementia., Results: For low P-B12 and normal P-B12 level groups, we included 53,089 patients in the primary P-B12 cohort and 13,656 patients in the secondary B12 treatment cohort. In the P-B12 cohort, hazard ratios for AD centered around one, regardless of follow-up period or treatment during follow-up. In the B12 treatment cohort, risk of AD was unaffected by low pre-treatment P-B12 levels, follow-up period and type of B12 treatment. Findings were similar for all-cause and vascular dementia., Conclusion: We found no associatio1n between low P-B12 levels and dementia. Associations were unaffected by B12 treatment. Results do not support routine screening for B12 deficiency in patients with suspected dementia.

Background: Substantial but inconclusive evidence suggests in utero exposure to influenza infection may be linked with Alzheimer's disease., Objectives: We examined whether individuals exposed in utero to the 1918 influenza pandemic are at increased risk of dementia., Patients/methods: In this cohort study, surveillance data were used to identify months when influenza activity was at its peak during the pandemic. Using birth dates, exposed and unexposed individuals were identified based on whether they were in utero during ≥1 of the peak months. The outcome, any type of dementia, was identified in population-based medical registries. Time and age at risk were restricted so exposed and unexposed had equal time at risk; diagnoses for dementia were assessed between ages 62 and 92, with a maximum of 30 years at risk. Poisson regression was used to estimate sex-adjusted incidence rate ratios (IRRs)., Results: We identified 106 479 exposed and 177 918 unexposed persons. Using the cumulative risk function, there were similar proportions of exposed and unexposed with a dementia diagnosis at 11.9% and 11.7%, respectively. Across all ages, the IRR for the association between in utero influenza exposure and any dementia was 1.01 (95% CI 0.99-1.04); for Alzheimer's disease, it was 0.97 (0.93-1.01). When stratified by age and sex, and when dementia type was examined, estimates of association were also null or close to null., Conclusions: Our study suggests there is likely not an association between in utero exposure to the 1918 influenza pandemic and dementia among those 62 and older., (© 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Cancer patients may be at decreased risk of Alzheimer's disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC), but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer's disease (main outcome) and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221) and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097). We followed individuals from the time of diagnosis, or corresponding date for matched comparators, until a dementia diagnosis, death, emigration, or 30 November 2013, whichever came first. We used stratified Cox regression adjusted for comorbidities to compute hazard ratios (HRs) associating NMSC with dementia. We computed cumulative risks of dementia, treating death as a competing risk. NMSC was associated with a HR of 0.95 (95% confidence interval [CI]: 0.92-0.98) for Alzheimer's disease and 0.92 (95% CI: 0.90-0.94) for all-cause dementia. HRs were similar for basal cell and squamous cell carcinoma, the two most common forms of NMSC. Estimates of risk reduction were more pronounced in the beginning of follow-up, reaching null after 5-10 years. At the end of follow-up (34 years), cumulative risk of Alzheimer's disease was 4.6% (95% CI: 4.4%-4.8%) among patients with NMSC vs. 4.7% (95% CI: 4.6%-4.9%) in the comparison cohort. In conclusion, NMSC was associated with 2%-10% reductions in relative risks of Alzheimer's disease and all-cause dementia. However, these small inverse associations may have been caused by ascertainment bias due to decreased awareness of NMSC tumors in persons with undiagnosed early cognitive impairment or by confounding from a more neuroprotective lifestyle among persons with NMSC.

Background and Purpose: Stroke is a risk factor for dementia, but the risk of dementia after different stroke types is poorly understood. We examined the long-term risk of dementia among survivors of any first-time stroke and of first-time ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage., Methods: We conducted a 30-year nationwide population-based cohort study using data from Danish medical databases (1982-2013) covering all Danish hospitals. We identified 84 220 ischemic stroke survivors, 16 723 intracerebral hemorrhage survivors, 9872 subarachnoid hemorrhage survivors, and 104 303 survivors of unspecified stroke types. Patients were aged ≥18 years and survived for at least 3 months after diagnosis. We formed a comparison cohort from the general population (1 075 588 patients without stroke, matched to stroke patients by age and sex). We computed absolute risks and hazard ratios of dementia up to 30 years after stroke., Results: The 30-year absolute risk of dementia among stroke survivors was 11.5% (95% confidence interval, 11.2%-11.7%). Compared with the general population, the hazard ratio (95% confidence interval) for dementia among stroke survivors was 1.80 (1.77-1.84) after any stroke, 1.72 (1.66-1.77) after ischemic stroke, 2.70 (2.53-2.89) after intracerebral hemorrhage, and 2.74 (2.45-3.06) after subarachnoid hemorrhage. Younger patients regardless of stroke type faced higher risks of poststroke dementia than older patients. The pattern of hazard ratios by stroke type did not change during follow-up and was not altered appreciably by age, sex, or preexisting diagnoses of vascular conditions., Conclusions: Stroke increases dementia risk. Survivors of intracerebral hemorrhage and subarachnoid hemorrhage are at particularly high long-term risk of poststroke dementia., (© 2016 American Heart Association, Inc.)

Background: Concerns have been raised about the risk of dementia associated with antiestrogen adjuvant therapy in breast cancer, but study results have been inconsistent. We examined whether tamoxifen or other endocrine therapy was associated with dementia risk in a large population of patients with breast cancer., Methods: We used Danish nationwide medical registries to identify patients with breast cancer diagnosed between 1990 and 2004, use of endocrine therapy, and subsequent diagnoses of dementia. We used Cox regression to estimate the risk of dementia among patients who received five years of tamoxifen or other endocrine therapies., Results: The study included 16,419 patients with breast cancer. In this cohort, 37% were unexposed to endocrine therapy, 9% had five years of tamoxifen therapy, and 54% had other endocrine regimens, some of them containing tamoxifen for less than five years with subsequent aromatase inhibitor therapy. Tamoxifen therapy was associated with a near-null risk of dementia [HR, 1.4; 95% confidence interval (CI), 1.0-1.9], and a null association was observed after death was taken into account as a competing risk (sub-HR, 1.0; 95% CI, 0.76-1.4)., Conclusions: No clinically relevant association between use of tamoxifen or other endocrine therapy and risk of dementia was observed., Impact: Our result contradicts earlier research findings suggesting tamoxifen and other endocrine therapies increase the risk of dementia in breast cancer patients.