Horizons in Human Aging Neuroscience: From Normal Neural Aging to Mental (Fr)Agility

While aging is an important risk factor for neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease, age-related cognitive decline can also manifest without apparent neurodegenerative changes. In this review, we discuss molecular, cellular, and network changes that occur during normal aging in the absence of neurodegenerative disease. Emerging findings reveal that these changes include metabolic alterations, oxidative stress, DNA damage, inflammation, calcium dyshomeostasis, and several other hallmarks of age-related neural changes that do not act on their own, but are often interconnected and together may underlie age-related alterations in brain plasticity and cognitive function. Importantly, age-related cognitive decline may not be reduced to a single neurobiological cause, but should instead be considered in terms of a densely connected system that underlies age-related cognitive alterations. We speculate that a decline in one hallmark of neural aging may trigger a decline in other, otherwise thus far stable subsystems, thereby triggering a cascade that may at some point also incur a decline of cognitive functions and mental well-being. Beyond studying the effects of these factors in isolation, considerable insight may be gained by studying the larger picture that entails a representative collection of such factors and their interactions, ranging from molecules to neural networks. Finally, we discuss some potential interventions that may help to prevent these alterations, thereby reducing cognitive decline and mental fragility, and enhancing mental well-being, and healthy aging

Ketamine treatment upon memory retrieval reduces fear memory in marmoset monkeys

Emotionally arousing experiences are retained very well as seen in posttraumatic stress disorder (PTSD). Various lines of evidence indicate that reactivation of these memories renders them labile which offers a potential time-window for intervention. We tested in non-human primates whether ketamine, administered during fear memory reactivation, affected passive (inhibitory) avoidance learning. For the consolidation of contextual emotional memory, the unescapable foot-shock paradigm in a passive avoidance task with two compartments (dark vs illuminated) was used. After entering the dark compartment, marmoset monkeys received four random foot-shocks (1 mA, 4 s) within 15-min. This stressful exposure increased the saliva cortisol and heart rate and impaired REM-sleep (p  <0.05). One week later the monkeys were re-exposed to the stressful situation for the reconsolidation of the fearful experience. During the re-exposure the monkeys were treated with ketamine (0.5 mg/kg) or saline. In week 3, the monkeys were placed in the experimental setting to test their memory for the fearful experience. In contrast to the vehicle-treated monkeys, who avoided the dark compartment, the ketamine-treated monkeys entered the dark compartment that was previously associated with the fearful experience (p < 0.05). Post-mortem analysis of the hippocampus showed that ketamine-treated animals exhibited less doublecortin positive neurons and BrdU-labeled cells in the dentate gyrus. This study reveals that a single low dose of ketamine, administered upon fear retrieval in monkeys, reduce contextual fear memory and attenuate neurogenesis in the hippocampus. These are important findings for considering ketamine as a potential candidate to target traumatic memories in PTSD

The Subjective Experience of Ageism: The Perceived Ageism Questionnaire (PAQ)

Ageism as perceived by older individuals has been recognized as a potential risk factor for physical and mental health. We aimed to develop a comprehensive scale that can quantify perceived ageism among aging individuals (55+), including both positive and negative stereotypes, prejudices, and discriminations. This effort resulted in an 8-item Perceived Ageism Questionnaire (PAQ-8), with good psychometric properties and a two-factor structure distinguishing a positive (3 items) and negative (5 items) subscale (Analysis 1; n = 500). This dimensionality was confirmed in a separate cross-validation sample (Analysis 2; n = 500). The subscales’ correlation patterns with individuals’ self-perceptions of aging and mental health variables (i.e., quality of life, mental well-being, depression, anxiety, loneliness and perceived stress) accorded with theoretical hypotheses and existing knowledge of the concept of ageism. The PAQ-8 can help to gather more standardized data of the level, role and impact of perceived ageism

Changes in perceived ageism during the COVID-19 pandemic: impact on quality of life and mental well-being among Dutch adults aged 55 and older

Objectives: The COVID-19 pandemic brought ageism to the forefront of public discourse. Negative ageism incurs more negative self-perceptions of aging, which affects physical and mental functioning. Whether negative ageism as perceived and experienced by older adults has worsened as the pandemic lingered, and how such changes impact quality of life (QoL) and mental well-being (MWB), remain urgent questions. Method: In a sample of adults aged 55 or older (n = 500), we aimed to address this by administering the Perceived Ageism Questionnaire twice during the pandemic (T1: between October 2020 and May 2021; T2: on average 45 wk after T1). Results: Higher levels of perceived negative ageism were associated with lower QoL and MWB, at least partially through its unfavorable effects on self-perceptions of aging, even after controlling for ageism experiences in the preceding year (at T2, corrected for T1). Furthermore, we found that perceived negative ageism increased from T1 to T2, which had negative implications for QoL/MWB. Opposite effects were found for perceived positive ageism, although less consistently. Conclusion: These patterns reveal that ageism as perceived and experienced by adults of 55 or older became stronger and more negative throughout the COVID-19 pandemic, which had detrimental implications for individuals' QoL and MWB. These disconcerting findings emphasize the importance of combatting negative ageism in our society.</p