Periodontitis and brain magnetic resonance imaging markers of Alzheimer's disease and cognitive aging.

INTRODUCTION: We examined the association of clinical, microbiological, and host response features of periodontitis with MRI markers of atrophy/cerebrovascular disease in the Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study of Oral Health. METHODS: We analyzed 468 participants with clinical periodontal data, microbial plaque and serum samples, and brain MRIs. We tested the association of periodontitis features with MRI features, after adjusting for multiple risk factors for Alzheimer's disease/Alzheimer's disease-related dementia (AD/ADRD). RESULTS: In fully adjusted models, having more teeth was associated with lower odds for infarcts, lower white matter hyperintensity (WMH) volume, higher entorhinal cortex volume, and higher cortical thickness. Higher extent of periodontitis was associated with lower entorhinal cortex volume and lower cortical thickness. Differential associations emerged between colonization by specific bacteria/serum antibacterial IgG responses and MRI outcomes. DISCUSSION: In an elderly cohort, clinical, microbiological, and serological features of periodontitis were associated with MRI findings related to ADRD risk. Further investigation of causal associations is warranted.

Family involvement and secondary traumatization in Holocaust survivor families: An actor-partner interdependence model.

OBJECTIVE: The study aimed to examine the interpersonal relationships between family involvement (i.e., emotional and behavioral strategies that underscore family members' well-being and familial legacy) and secondary traumatization (i.e., symptoms of distress resulting from close contact with a traumatized individual) in Holocaust survivors and comparison families. We assessed levels of family involvement and secondary traumatization in children and grandchildren of survivors (Holocaust G2 and G3) and comparisons. Next, we examined whether there are within and between generation relationships between family involvement and secondary traumatization (i.e., G2's family involvement affects G3's secondary traumatization and vice versa). METHOD: The sample included 92 Holocaust G2-G3 dyads and 67 equivalent comparison dyads (comparison G2 and G3 of European origin, whose parents or grandparents were not in Nazi/pro-Nazi dominated countries). Participants answered questionaries on background characteristics, family involvement, and secondary traumatization. RESULTS: Secondary traumatization was significantly higher among Holocaust G2 and G3 than comparison G2 and G3, respectively. Family involvement was significantly higher among Holocaust G2 than comparison G2. An Actor-Partner Interdependence model showed that participants who reported greater family involvement reported higher secondary traumatization in all families (i.e., an actor effect). A significant partner effect was found only in Holocaust families. In these families, greater family involvement in one generation was related to higher secondary traumatization in the other generation. CONCLUSIONS: The findings suggest a unique interpersonal mechanism of intergenerational transmission of trauma in Holocaust families that appears to affect both generations, which may help design multigenerational interventions with survivor families, focusing on family involvement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Event centrality and secondary traumatization among Holocaust survivors' offspring and grandchildren: A three-generation study.

The present study examined the intergenerational transmission of the Holocaust trauma in relation to levels of secondary traumatization and event centrality across three generations in a cross-sectional survey. Participants included 92 Holocaust survivor-offspring-grandchild triads (Holocaust G1-G2-G3) and 67 comparison triads (Comparison G1-G2-G3). Holocaust G1 reported higher levels of post-traumatic stress disorder (PTSD) symptoms relative to Comparison G1. Holocaust G2 and G3 reported significantly higher secondary traumatization relative to Comparison G2 and G3, respectively. Holocaust G3 also reported significantly higher scores in event centrality relative to Comparison G3. In survivor families, the indirect effect of PTSD symptoms in Holocaust G1 predicted Holocaust G2's secondary traumatization, which subsequently predicted Holocaust G3's secondary traumatization. Moreover, PTSD symptoms in Holocaust G1 predicted Holocaust G3's event centrality through secondary traumatization in both Holocaust G2 and G3 and event centrality in Holocaust G2. In the comparison groups, trauma transmission was not observed in three generations. Findings elucidate unique intergenerational transmission of the Holocaust trauma in survivor families, which comprise both personal and societal constituents. Moreover, the findings show that event centrality is a distinctive mechanism in intergenerational transmission in survivor families.

Which Factors do Older Adults Consider When Estimating the Time Left for Them to Live?

Objectives: The present study examines which factors older adults consider as important when rating their subjective nearness-to-death (SNtD), as well as the associations between corresponding variables as reported in a multidimensional questionnaire and responses on a SNtD question. In addition, we examine whether importance ratings fit or diverge from the actual associations between corresponding variables and SNtD. Method: Two hundred and seventy-two participants (average age 80.75) reported their health and functioning, their SNtD, and the importance of each of 13 preselected factors in evaluating SNtD. Results: Respondents considered physical functioning and psychological factors as the most important factors to their SNtD evaluation, and genetic factors (i.e., age, gender, parental longevity) as the least important. Ratings of importance were strongly and positively correlated with the strength of the associations between the corresponding variables and SNtD. Discussion: Older adults appear to have implicit knowledge of the factors that affect their SNtD. Yet, this knowledge is sometimes biased and does not necessarily represent variables that have been identified as related to actual longevity.

Intranasal exposure to manganese disrupts neurotransmitter release from glutamatergic synapses in the central nervous system in vivo.

Chronic exposure to aerosolized manganese induces a neurological disorder that includes extrapyramidal motor symptoms and cognitive impairment. Inhaled manganese can bypass the blood-brain barrier and reach the central nervous system by transport down the olfactory nerve to the brain's olfactory bulb. However, the mechanism by which Mn disrupts neural function remains unclear. Here we used optical imaging techniques to visualize exocytosis in olfactory nerve terminals in vivo in the mouse olfactory bulb. Acute Mn exposure via intranasal instillation of 2-200 µg MnCl(2) solution caused a dose-dependent reduction in odorant-evoked neurotransmitter release, with significant effects at as little as 2 µg MnCl(2) and a 90% reduction compared to vehicle controls with a 200 µg exposure. This reduction was also observed in response to direct electrical stimulation of the olfactory nerve layer in the olfactory bulb, demonstrating that Mn's action is occurring centrally, not peripherally. This is the first direct evidence that Mn intoxication can disrupt neurotransmitter release, and is consistent with previous work suggesting that chronic Mn exposure limits amphetamine-induced dopamine increases in the basal ganglia despite normal levels of dopamine synthesis (Guilarte et al., J Neurochem 2008). The commonality of Mn's action between glutamatergic neurons in the olfactory bulb and dopaminergic neurons in the basal ganglia suggests that a disruption of neurotransmitter release may be a general consequence wherever Mn accumulates in the brain and could underlie its pleiotropic effects.

Functional rehabilitation of cadmium-induced neurotoxicity despite persistent peripheral pathophysiology in the olfactory system.

Intranasal exposure to the heavy metal cadmium has been linked to olfactory dysfunction and neurotoxicity. Here, we combine optical imaging of in vivo neurophysiology, genetically defined anatomical tract tracing, mass spectrometry, and behavioral psychophysical methods to evaluate the persistent harmful effects of acute intranasal exposure to cadmium in a mouse model and to investigate the functional consequences of sensory rehabilitation training. We find that an acute intranasal instillation of cadmium chloride leads to an accumulation of cadmium in the brain's olfactory bulb that persists for at least 4 weeks. This is accompanied by persistent severe pathophysiology of the olfactory nerve, a gradual reduction in axonal projections from the olfactory epithelium, and complete impairment on an olfactory detection task. Remarkably, 2 weeks of odorant-guided operant conditioning training proved sufficient to restore olfactory detection performance to control levels in cadmium-exposed mice. Optical imaging from rehabilitated mice showed that this training did not cause any detectable restoration of olfactory nerve function, suggesting that the recovery of function was mediated by central neuroplasticity in which the brain learned to interpret the degraded sensory input. These data demonstrate that sensory learning can mask even severe damage from neurotoxicants and suggest that explicit sensory training may be useful in rehabilitation of olfactory dysfunction.

In vivo visualization of olfactory pathophysiology induced by intranasal cadmium instillation in mice.

Intranasal exposure to cadmium has been related to olfactory dysfunction in humans and to nasal epithelial damage and altered odorant-guided behavior in rodent models. The pathophysiology underlying these deficits has not been fully elucidated. Here we use optical imaging techniques to visualize odorant-evoked neurotransmitter release from the olfactory nerve into the brain's olfactory bulbs in vivo in mice. Intranasal cadmium chloride instillations reduced this sensory activity by up to 91% in a dose-dependent manner. In the olfactory bulbs, afferents from the olfactory epithelium could be quantified by their expression of a genetically encoded fluorescent marker for olfactory marker protein. At the highest dose tested, cadmium exposure reduced the density of these projections by 20%. In a behavioral psychophysical task, mice were trained to sample from an odor port and make a response when they detected an odorant against a background of room air. After intranasal cadmium exposure, mice were unable to detect the target odor. These experiments serve as proof of concept for a new approach to the study of the neural effects of inhaled toxicants. The use of in vivo functional imaging of the neuronal populations exposed to the toxicant permits the direct observation of primary pathophysiology. In this study optical imaging revealed significant reductions in odorant-evoked release from the olfactory nerve at a cadmium chloride dose two orders of magnitude less than that required to induce morphological changes in the nerve in the same animals, demonstrating that it is a more sensitive technique for assessing the consequences of intranasal neurotoxicant exposure. This approach is potentially useful in exploring the effects of any putative neurotoxicant that can be delivered intranasally.