ImportanceAdults with Alzheimer disease and related dementias (ADRD) are particularly vulnerable to the direct and indirect effects of the COVID-19 pandemic. Deaths associated with ADRD increased substantially in pandemic year 1. It is unclear whether mortality associated with ADRD declined when better prevention strategies, testing, and vaccines became widely available in year 2.ObjectiveTo compare pandemic-era excess deaths associated with ADRD between year 1 and year 2 overall and by age, sex, race and ethnicity, and place of death.Design, Setting, and ParticipantsThis time series analysis used all death certificates of US decedents 65 years and older with ADRD as an underlying or contributing cause of death from January 2014 through February 2022.ExposureCOVID-19 pandemic era.Main Outcomes and MeasuresPandemic-era excess deaths associated with ADRD were defined as the difference between deaths with ADRD as an underlying or contributing cause observed from March 2020 to February 2021 (year 1) and March 2021 to February 2022 (year 2) compared with expected deaths during this period. Expected deaths were estimated using data from January 2014 to February 2020 fitted with autoregressive integrated moving average models.ResultsOverall, 2 334 101 death certificates were analyzed. A total of 94 688 (95% prediction interval [PI], 84 192-104 890) pandemic-era excess deaths with ADRD were estimated in year 1 and 21 586 (95% PI, 10 631-32 450) in year 2. Declines in ADRD-related deaths in year 2 were substantial for every age, sex, and racial and ethnic group evaluated. Pandemic-era ADRD-related excess deaths declined among nursing home/long-term care residents (from 34 259 [95% PI, 25 819-42 677] in year 1 to −22 050 [95% PI, −30 765 to −13 273] in year 2), but excess deaths at home remained high (from 34 487 [95% PI, 32 815-36 142] in year 1 to 28 804 [95% PI, 27 067-30 571] in year 2).Conclusions and RelevanceThis study found that large increases in mortality with ADRD as an underlying or contributing cause of death occurred in COVID-19 pandemic year 1 but were largely mitigated in pandemic year 2. The most pronounced declines were observed for deaths in nursing home/long-term care settings. Conversely, excess deaths at home and in medical facilities remained high in year 2.

IntroductionEpidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases such as confounding, diagnostic bias, and selective survival have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to generate and compare estimates for the cancer-dementia association using different analytical specifications designed to address different sources of bias.MethodsWe included 140,959 UK Biobank participants aged ≥ 55 without dementia before enrollment, and with linked primary care data. We used cancer registry data to identify cases of prevalent cancer before UK Biobank enrollment and incident cancer after enrollment. We used multivariable-adjusted Cox models to evaluate the associations of prevalent and incident cancer with incidence of all-cause dementia, Alzheimer’s disease (AD), and vascular dementia. And we systematically evaluated each potential source of bias.ResultsThe cohort accumulated 3,310 incident dementia diagnoses over a median of 12.3 years of follow-up. All-site incident cancer was positively associated with all-cause dementia risk (hazard ratio [HR]=1.14, 95% CI: 1.02-1.29). The adjusted HR for prevalent cancer was 1.03 (95% CI: 0.92-1.17). Results were similar for vascular dementia. AD dementia was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR=1.83, 95% CI: 1.48-2.36), suggesting diagnostic bias.ConclusionIncident cancer diagnoses were associated with a higher risk of subsequent dementia diagnoses. Increased chance of dementia diagnosis associated with increased health care utilization after a cancer diagnosis may be a source of bias in electronic health records-based studies.

Background The objective of this study was to evaluate associations of diabetes overall, type 1 diabetes (T1D), and type 2 diabetes (T2D) with breast cancer (BCa) risk. Methods We included 250,312 women aged 40–69 years between 2006 and 2010 from the UK Biobank cohort. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated for associations of diabetes and its two major types with the time from enrollment to incident BCa. Results We identified 8182 BCa cases during a median follow-up of 11.1 years. We found no overall association between diabetes and BCa risk (aHR = 1.02, 95% CI = 0.92–1.14). When accounting for diabetes subtype, women with T1D had a higher risk of BCa than women without diabetes (aHR = 1.52, 95% CI = 1.03–2.23). T2D was not associated with BCa risk overall (aHR = 1.00, 95% CI = 0.90–1.12). However, there was a significantly increased risk of BCa in the short time window after T2D diagnosis. Conclusions Though we did not find an association between diabetes and BCa risk overall, an increased risk of BCa was observed shortly after T2D diagnosis. In addition, our data suggest that women with T1D may have an increased risk of BCa.

Background and Objectives: Cancer survivors are less likely than comparably-aged individuals without a cancer history to develop Alzheimer's disease and related dementias (ADRD). We investigated the association between cancer history and structural magnetic resonance imaging (MRI) markers for ADRD risk, using linear mixed-effects models to assess differences at the mean values of MRI markers and quantile regression to examine whether the association varies across the distribution of MRI markers of brain aging. Methods: Among UK Biobank participants with ≥1 brain MRI, we considered total gray matter volume, total brain volume, hippocampal volume, white matter hyperintensity volume, and mean cortical thickness in the Alzheimer's disease (AD) signature region. Cancer history was ascertained from national registry and self-report. We first specified linear mixed models with random intercepts to assess mean differences in MRI markers according to cancer history. Next, to examine whether effects of cancer history on these markers varies across the ADRD risk distribution, we specified quantile regression models to assess differences in quantile cut-points of the distribution of MRI markers according to cancer history. Models adjusted for demographics, APOE-ε4 status, and health behaviors. Results: The sample included 42,242 MRIs on 37,588 participants with no cancer history (mean age 64.1 years), and 6,073 MRIs on 5,514 participants with a cancer diagnosis prior to MRI (mean age 66.7 years). Cancer history was associated with smaller mean hippocampal volume (b=-19 mm3, 95% confidence interval [CI]=-36, -1) and lower mean cortical thickness in the AD signature region (b=-0.004 mm, 95% CI=-0.007, -0.000). Quantile regressions indicated cancer history had larger effects on high quantiles of white matter hyperintensities (10th percentile b=-49 mm3, 95% CI=-112, 19; 90th percentile b=552 mm3, 95% CI= 250, 1002) and low quantiles of cortical thickness (10th percentile b=-0.006 mm, 95% CI=-0.011, -0.000; 90th percentile b=0.003 mm3, 95% CI=-0.003, 0.007), indicating individuals most vulnerable to ADRD were more affected by cancer history. Discussion: We found no evidence that cancer history was associated with less ADRD-related neurodegeneration. To the contrary, adults with cancer history had worse MRI indicators of dementia risk. Adverse associations were largest in the highest-risk quantiles of neuroimaging markers.