C-reactive protein levels and depression in older and younger adults - A study of 19,947 individuals. The Tromsø study

In recent years, a connection between depression and inflammation has been established, with a range of immunological changes, both cellular and humoral, presenting during depressive states (Beydoun et al., 2016; Haapakoski et al., 2015; Wium-Andersen et al., 2013). Furthermore, there seems to be a dose-response relationship between depression and inflammation, in the sense that the more severe the depression, the higher the level of systemic inflammation markers, most notably expressed as elevated levels of C-reactive protein (CRP) in peripheral blood (Kohler-Forsberg et al., 2017). Accordingly, CRP has been suggested as a marker of depression severity and depression subtypes, as well as an indicator of specific symptom profiles (Jokela et al., 2016). Furthermore, inflammation has been suggested as a target for treatment with immunomodulatory drugs (Alexopoulos and Morimoto, 2011; Kohler et al., 2014). However, the research populations are predominantly younger adults, mainly in clinical settings, and there are few community-based studies providing comparative analyses of age-groups, or focusing specifically on the older population. For those that do, the results are inconsistent, as some demonstrate an association between CRP and depression (Bondy et al., 2021; Sonsin-Diaz et al., 2020; White et al., 2017), while others do not (Baune et al., 2012; Bremmer et al., 2008; Eurelings et al., 2015; Penninx et al., 2003). Thus, it is still unclear whether the inflammation in depression unfolds to the same extent in depressed older adults as in younger adults, and how the severity of the depression relates to inflammation in different age groups

Examining Associations Between Smartphone Use and Clinical Severity in Frontotemporal Dementia: Proof-of-Concept Study

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged <65 years. Several challenges to conducting in-person evaluations in FTLD illustrate an urgent need to develop remote, accessible, and low-burden assessment techniques. Studies of unobtrusive monitoring of at-home computer use in older adults with mild cognitive impairment show that declining function is reflected in reduced computer use; however, associations with smartphone use are unknown.ObjectiveThis study aims to characterize daily trajectories in smartphone battery use, a proxy for smartphone use, and examine relationships with clinical indicators of severity in FTLD.MethodsParticipants were 231 adults (mean age 52.5, SD 14.9 years; n=94, 40.7% men; n=223, 96.5% non-Hispanic White) enrolled in the Advancing Research and Treatment of Frontotemporal Lobar Degeneration (ARTFL study) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS study) Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Mobile App study, including 49 (21.2%) with mild neurobehavioral changes and no functional impairment (ie, prodromal FTLD), 43 (18.6%) with neurobehavioral changes and functional impairment (ie, symptomatic FTLD), and 139 (60.2%) clinically normal adults, of whom 55 (39.6%) harbored heterozygous pathogenic or likely pathogenic variants in an autosomal dominant FTLD gene. Participants completed the Clinical Dementia Rating plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration Behavior and Language Domains (CDR+NACC FTLD) scale, a neuropsychological battery; the Neuropsychiatric Inventory; and brain magnetic resonance imaging. The ALLFTD Mobile App was installed on participants' smartphones for remote, passive, and continuous monitoring of smartphone use. Battery percentage was collected every 15 minutes over an average of 28 (SD 4.2; range 14-30) days. To determine whether temporal patterns of battery percentage varied as a function of disease severity, linear mixed effects models examined linear, quadratic, and cubic effects of the time of day and their interactions with each measure of disease severity on battery percentage. Models covaried for age, sex, smartphone type, and estimated smartphone age.ResultsThe CDR+NACC FTLD global score interacted with time on battery percentage such that participants with prodromal or symptomatic FTLD demonstrated less change in battery percentage throughout the day (a proxy for less smartphone use) than clinically normal participants (P<.001 in both cases). Additional models showed that worse performance in all cognitive domains assessed (ie, executive functioning, memory, language, and visuospatial skills), more neuropsychiatric symptoms, and smaller brain volumes also associated with less battery use throughout the day (P<.001 in all cases).ConclusionsThese findings support a proof of concept that passively collected data about smartphone use behaviors associate with clinical impairment in FTLD. This work underscores the need for future studies to develop and validate passive digital markers sensitive to longitudinal clinical decline across neurodegenerative diseases, with potential to enhance real-world monitoring of neurobehavioral change

Brain volumetric deficits in MAPT mutation carriers: a multisite study

Objective: MAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach. Methods: We studied 22 symptomatic carriers (age 54.7 ± 9.1, 13 female) and 43 presymptomatic carriers (age 39.2 ± 10.4, 21 female). Symptomatic carriers’ clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson’s disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype. Results: Symptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volume

Urethral Polyembolokoilamania: An Unusual Manifestation of Behavioral and Psychological Symptoms of Dementia (BPSD)

Behavioral and psychological symptoms of dementia (BPSD) have varied presentations and frequently occur throughout the trajectory of dementia. Hypersexuality and general disinhibition of societal and cultural norms are commonly documented in all types of dementia. However, sparse literature exists on polyembolokoilamania (insertion of foreign objects in bodily orifices) without a sexual component as a dementia-related symptom. We review an unusual case of a 94-year-old man who presented with urethral polyembolokoilamania without hypersexuality or other behavioral disinhibition. We highlight clinical considerations of managing urethral polyembolokoilamania in an elderly patient without a previous neurocognitive disorder diagnosis. A multidisciplinary team approach with input from Internal Medicine, Urology, Psychiatry, and Neurology lead to a comprehensive assessment of a patient that could have been managed solely as a surgical case. This spearheaded a formal diagnosis of neurocognitive disorder—guiding successful management, follow-up, caregiver education, and reduction of further harm

Providing quality end-of-life care to older people in the era of COVID-19: perspectives from five countries

This paper will explore the key challenges currently afoot in providing quality end-of-life care to older people in the COVID pandemic from the perspective of clinicians and researchers from five countries. We explore ways to preserve the same level of care our patients already receive and to avoid care disparities at the end of life, concluding with suggestions for clinicians trying to achieve this