A multi-site 99mTc-HMPAO SPECT study of cerebral blood flow in a community sample of patients with major depression.

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18-65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99mTc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18-65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.

Trends in Mortality Rates Among Medicare Enrollees With Alzheimer Disease and Related Dementias Before and During the Early Phase of the COVID-19 Pandemic.

IMPORTANCE: The COVID-19 pandemic fundamentally altered the delivery of health care in the United States. The associations between these COVID-19-related changes and outcomes in vulnerable patients, such as among persons with Alzheimer disease and related dementias (ADRD), are not yet well understood. OBJECTIVE: To determine the association between regional rates of COVID-19 infection and excess mortality among individuals with ADRD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used data from beneficiaries of 100% fee-for-service Medicare Parts A and B between January 1, 2019, and December 31, 2020, to assess age- and sex-adjusted mortality rates. Participants were 53 640 888 Medicare enrollees 65 years of age or older categorized into 4 prespecified cohorts: enrollees with or without ADRD and enrollees with or without ADRD residing in nursing homes. EXPOSURES: Monthly COVID-19 infection rates by hospital referral region between January and December 2020. MAIN OUTCOMES AND MEASURES: Mortality rates from March through December 2020 were compared with those from March through December 2019. Excess mortality was calculated by comparing mortality rates in 2020 with rates in 2019 for specific, predetermined groups. Means were compared using t tests, and 95% CIs were estimated using the delta method. RESULTS: This cross-sectional study included 26 952 752 Medicare enrollees in 2019 and 26 688 136 enrollees in 2020. In 2019, the mean (SD) age of community-dwelling beneficiaries without ADRD was 74.1 (8.8) years and with ADRD was 82.6 (8.4) years. The mean (SD) age of nursing home residents with ADRD (83.6 [8.4] years) was similar to that for patients without ADRD (79.7 [8.8] years). Among patients diagnosed as having ADRD in 2019, 63.5% were women, 2.7% were Asian, 9.2% were Black, 5.7% were Hispanic, 80.7% were White, and 1.7% were identified as other (included all races or ethnicities other than those given); the composition did not change appreciably in 2020. Compared with 2019, adjusted mortality in 2020 was 12.4% (95% CI, 12.1%-12.6%) higher among enrollees without ADRD and 25.7% (95% CI, 25.3%-26.2%) higher among all enrollees with ADRD, with even higher percentages for Asian (36.0%; 95% CI, 32.6%-39.3%), Black (36.7%; 95% CI, 35.2%-38.2%), and Hispanic (40.1%; 95% CI, 37.9%-42.3%) populations with ADRD. The hospital referral region in the lowest quintile for COVID-19 infections in 2020 had no excess mortality among enrollees without ADRD but 8.8% (95% CI, 7.5%-10.2%) higher mortality among community-dwelling enrollees with ADRD and 14.2% (95% CI, 12.2%-16.2%) higher mortality among enrollees with ADRD living in nursing homes. CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that the COVID-19 pandemic may be associated with excess mortality among older adults with ADRD, especially for Asian, Black, and Hispanic populations and people living in nursing homes, even in areas with low COVID-19 prevalence.