The aim of the study was to examine potential cognitive, mood (depression and anxiety) and behavioral changes that may be related to the quarantine and the lockdown applied during the COVID-19 pandemic in Greek older adults with mild cognitive impairment (MCI), and AD dementia in mild and moderate stages. Method: 407 older adults, diagnosed either with MCI or AD dementia (ADD), were recruited from the Day Centers of the Greek Association of Alzheimer Disease and Related Disorders (GAADRD). Neuropsychological assessment was performed at baseline (at the time of diagnosis) between May and July of 2018, as well as for two consecutive follow-up assessments, identical in period, in 2019 and 2020. The majority of participants had participated in non-pharmacological interventions during 2018 as well as 2019, whereas all of them continued their participation online in 2020. Results: Mixed measures analysis of variance showed that participants’ ‘deterioration difference—D’ by means of their performance difference in neuropsychological assessments between 2018–2019 (D1) and 2019–2020 (D2) did not change, except for the FUCAS, RAVLT, and phonemic fluency tests, since both groups resulted in a larger deterioration difference (D2) in these tests. Additionally, three path models examining the direct relationships between performance in tests measuring mood, as well as everyday functioning and cognitive measures, showed that participants’ worsened performance in the 2019 and 2020 assessments was strongly affected by NPI performance, in sharp contrast to the 2018 assessment. Discussion: During the lockdown period, MCI and ADD patients’ neuropsychological performance did not change, except from the tests measuring verbal memory, learning, and phonemic fluency, as well as everyday functioning. However, the natural progression of the MCI as well as ADD condition is the main reason for participants’ deterioration. Mood performance became increasingly closely related to cognition and everyday functioning. Hence, the role of quarantine and AD progression are discussed as potential factors associated with impairments.

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Stress is a significant contributor to the development and progression of substance use disorders (SUDs) and is problematic as it is unavoidable in daily life. Therefore, it is important to understand the neurobiological mechanisms that underlie the influence of stress on drug use. We have previously developed a model to examine the contribution of stress to drug-related behavior by administering a stressor, electric footshock stress, daily at the time of cocaine self-administration in rats resulting in an escalation of cocaine intake. This stress-induced escalation of cocaine intake involves neurobiological mediators of stress and reward such as cannabinoid signaling. However, all of this work has been conducted in male rats. Here we test the hypothesis that repeated daily stress can produce an escalation of cocaine in both male and female rats. We further hypothesize that cannabinoid receptor 1 (CB1R) signaling is recruited by repeated stress to influence cocaine intake in both male and female rats. Male and female Sprague-Dawley rats self-administered cocaine (0.5 mg/kg/inf, i.v.) during a modified short-access paradigm wherein the 2-hr access was separated into 4-30 min self-administration blocks separated by 4-5 min drug free period. Footshock stress produced a significant escalation of cocaine intake similarly in both male and female rats. Female stress-escalated rats did display greater time-out non-reinforced responding and greater front-loading behavior. In males, systemic administration of a CB1R inverse agonist/antagonist Rimonabant only attenuated cocaine intake in rats with a history of combined repeated stress and cocaine self-administration. However, in females, Rimonabant attenuated cocaine intake in the no stress control group but only at the highest dose of Rimonabant (3 mg/kg, i.p.) suggesting that females show a greater sensitivity to CB1R antagonism. However, female rats with a history of stress showed even greater sensitivity to CB1R antagonism as both doses of Rimonabant (1, 3 mg/kg) attenuated cocaine intake in stress-escalated rats similar to males. Altogether these data demonstrate that stress can produce significant changes in cocaine self-administration and suggests that repeated stress at the time of cocaine self-administration recruits CB1Rs to regulate cocaine-taking behavior across sexes.