INTRODUCTION

The pandemic caused by SARS-CoV2, the etiologic agent of COVID-19, represents an unprecedented social on April 2022, there have been 5, 950, 424 accumulated cases and 337, 435 deaths related to COVID-19 since the pandemic began. Lockdown started on March 23rd, 2020, and it extended over a year, with a peak (average number of infections per day) on January 20th, 2021 (^{Secretaría de Salud, 2020}).

Since older adults (OA) were particularly susceptible to develop severe manifestations of the disease and complications that increase disability and decrease quality of life (^{Sepulveda-Loyola et al., 2020}), it was a priority that this population sector remains isolated as an effective prevention strategy; however, this represented a new challenge for older adults’ mental health. At this point, two different terms must be introduced: a) Social isolation, which is defined as having low quality of contact with others; it is objective and can be measured using observations of an individual’s social network (^{Freedman & Nicolle, 2020}) , b) Loneliness, which refers to the adverse emotional state experienced subjectively related to the perception of unsatisfied intimate and social needs (^{Luanaigh & Lawlor, 2008}).

Prevalence suggests that nearly one-third of older adults experience loneliness and/or social isolation, and a subset (5%) reports often or always feeling lonely (^{Kotwal et al., 2021}). Although loneliness does not have the status of a clinical disease by itself, it is associated with several negative health outcomes like stress, sleep disturbances, depressive symptoms, cognitive impairment, coronary heart disease, stroke, and mortality (^{Akhter-Khan et al., 2021}).

On the other hand, partial or total restriction of social interaction could generate negative consequences for the health of OA, especially in those with chronic diseases, disabilities, and geriatric syndromes (^{Sepulveda-Loyola et al., 2020}).

Social isolation may cause impairment in social recognition memory, thereby potentially increasing risk of long-term perceptions of loneliness (i.e., animals exposed to social isolation later have difficulties with social recognition; ^{Mumtaz, Khan, Zubair, & Dehpour, 2018}). However, it does not affect other types of memory. This may be related to the specific neural network which processes social information in the mammalian brain which includes: olfactory bulbs, medial nucleus of the amygdala, lateral septum, and the pyramidal layer of neurons of the hippocampus which makes a trajectory in the shape of an inverted C, specially in the region called CA2 (^{Leser & Wagner, 2015}).

We aim to examine the influence of loneliness and social isolation in daily cognitive function in a sample of Mexican older adults living in the community during the first wave of COVID-19 pandemic lockdown and assess characteristics associated with loneliness.

METHOD

RESULTS

From a total of 308 participants, three participants were excluded for incomplete surveys. Finally, 305 participants were included for statistical analysis from which 75.7% were women (n = 233) with a mean age of 65.4 years (SD = ± 7.9), only 8.4% reported COVID-19 symptoms. Most subjects were married/civil union (48.7%). Those who lived alone were distributed within the following groups: single (17.2%), widowed (14.6%), and divorced/living alone (19% / 48%). The average years of education was 15 (SD = ± 3.0). In terms of occupation, most participants were retired (33.1%), followed by economically active people (25.9%) and housewives (21.3%) (Table 1).

Up to 84.0% (n = 259) had loneliness with a mean affirmative item in the De Jong Gierveld Loneliness scale of 4.13 (SD = ± 1.1) while 79.9% (n = 246) of the participants identified themselves with social isolation using the EPII scale (Table 1). On the other hand, the E-Cog total score was 57.6 (SD = ± 18.8) and average score 1.4 (SD = ± 0.49) with the following highest scores for these cognitive domains: memory (14.1, SD = ± 5.5), language (13.7, SD = ± 5.0), and visuospatial (9.1, SD = ± 3.1).

While 73.1% of the participants reported memory complaint, evidenced with affirmative items in the 7-Memory Questionnaire, the mean affirmative items were 2.2 (SD = ± 2.0), and the major complaints were: in difficulty of remembering things from one second to the next (48.9%) and remembering a short list of items (43.3%).

Loneliness scale (rho .219, p = < .005), EPII Physical Distancing and Quarantine (rho .178, p = < .05) and SMC (rho .68 p = < .001) showed positive Spearman correlation.

Using the cut-off point suggested by ^{van Hartel et al. (2018)}, 49.1% (n = 150) had a score < 1.31 indicating normal cognition, while 50.9% (n = 154) had a higher score, corresponding to cognitive impairment (^{van Harten et al., 2018}). The perception of loneliness was higher in the second group (76.62% vs. 73.3%), as well as social isolation (87.66% vs. 71.33%) and SMC (54% vs. 90.2%) demographic characteristics were similar in both groups (Table 2, Figure 1).    

Figure 1 Distribution of participants: Participants with worse cognitive performance as measured by E-Cog are shown in grey, while participants with normal performance are shown in black columns. Greater loneliness, isolation, and subjective memory complaint are observed in participants with a score > 1.31. 

Table 3 describes the multivariate regression model adjusted by age, sex, and education. There’s a negative and statistically significant association with loneliness (β = -.046; 95% CI = [-.080, -.013]; p = .007) and isolation (β = -.168; 95% CI = [-.089, -.018]; p = .003), while SMC had a positive association with ECog (β = .812; 95% CI = [-.16, -.11]; p = < .001), this model explains the 15% of the variability of the E-Cog score.    

DISCUSSION AND CONCLUSION

In this study, with data from a remote survey conducted in older adults living in the community, carried out during the first wave of the COVID-19 pandemic in Mexico, we found a negative and statistically significant association with self-perception of loneliness and social isolation and daily cognitive function, in contrast, SMC was higher in those with worse daily cognitive performance.

The frequency of loneliness in the participants is higher than that reported in the literature, being 84% compared to 30.9% and 43.1% reported by a cohort of older adults in California and Canada, respectively, during the COVID-19 pandemic (^{Savage et al., 2021}). This feeling of loneliness appears to be even greater compared to the increase reported during confinement, for instance, in a cohort study of older adults in primary care in Hong Kong (n = 538, age = 70.6 + 6.1). Loneliness measured by the De Jong Gierveld scale during the COVID-19 pandemic increased from 1.6 to 2.9 positive items on average while the participants in our study had an average of 4.13 (1.1) positive items (^{Wong et al., 2020}). Consistent with previous studies (^{Zovetti, Rossetti, Perlini, Brambilla, & Bellani, 2021}), most of the participants with loneliness were women.

Older adults with the lowest report of loneliness were found in the lowest E-Cog scores, that is, those who referred loneliness during lockdown had a worse performance in the global E-Cog score. These findings coincide with those reported by ^{Kim, Beam, Greenberg, and Burke (2020)} who points out that loneliness predicts worse performance in several cognitive domains such as immediate memory, visuospatial skills, and processing speed (^{Kim et al., 2020}).

In two previous studies, carried out as cohorts from China and Argentina using the E-Cog scale, the additional memory domains, such as language, divided attention, and planning (^{Marshall et al., 2014}) were associated with a lesser impact on functionality compared to FAQ (Functional Assessment Questionary) without showing an association with hippocampal hypometabolism, and the ROI (Regions of Interest) of Alzheimer’s disease compared to the memory-related domain (^{Hsu et al., 2017}) which could suggest greater usefulness for the detection of amnestic cognitive profiles compared to other scales.

The mechanism that explains how loneliness impacts on cognitive functions remarks a strong relationship with chronic stress underlying prolonged periods of loneliness, increased glucocorticoid activation and hypercortisolism. These physiological alterations occur differently depending on the loneliness’ period length. Thus, transient loneliness can activate the hypothalamic-pituitary-adrenal (HPA) axis to negatively regulate inflammatory responses while persistent loneliness is associated with increased production of pro-inflammatory cytokines such as: tumor necrosis factor-alpha (TNF-α), Interleukin 1-beta (IL-1β), Interleukin 6 (IL-6), among others (COX-2 and iNOS; ^{Akhter-Khan et al., 2021}; ^{Bzdok & Dunbar, 2020}). This state of chronic inflammation decreases dopamine signaling, circadian rhythm, and monoamine levels (serotonin, norepinephrine, and dopamine) which in turn synaptic plasticity and neuronal survival decrease. Consequently, neurodegeneration increases, perpetuating axis dysfunction HPA and physiological reward mechanisms (^{Wilkialis et al., 2021}). In cohort studies, loneliness was associated with poorer performance in different types of memory, with a faster decline in semantic memory compared to episodic memory (^{Shankar, Hamer, McMunn, & Steptoe, 2013}).

Similar with the English Longitudinal Study of Aging, were social isolation is associated with decreased episodic memory and verbal fluency after a 4-year follow-up period (^{Shankar et al., 2013}) a Spanish study in older adults showed that greater social isolation is associated with lower scores in neuropsychological assessment batteries, reflected in both the global cognitive score and worse performance in verbal fluency and forward digits (^{Lara et al., 2019}). In animal models, these findings have been related to alterations in the CA2 region of the hippocampus, (^{Leser & Wagner, 2015}; ^{Mumtaz et al., 2018}) therefore, it is plausible to detect social isolation as an additional risk factor for cognitive impairment. In general, social interaction generates demands that protect and maintain cognition, leaving isolated people vulnerable to impaired cognition (^{Burns et al., 2020}; ^{Kim et al., 2020}). Thus, we propose that social isolation in the participants of our study comes from an emergent situation as part of the preventive measures of contagion.

Previous studies with older adults during confinement as a result of COVID-19 in China report that being a woman and living alone carries a greater risk of perceived isolation since they depend more on family members and friends for social support. This was reduced due to social distancing during COVID-19 (^{Brailean, Steptoe, Batty, Zaninotto, & Llewellyn, 2019}). However, this condition of physical distancing does not imply the deprivation of the feeling of accompaniment, protection or closeness to people in the form of an emotional connection as it occurs when experiencing loneliness. That is, the significant effects of loneliness, conceptualized as (self-perceived) social isolation, on general cognitive function can be found together but not always (^{Burns et al., 2020}; ^{Kim et al., 2020}).

Regarding SMC, it is known that up to 25 to 50% of older adults living in the community refer it to first-contact doctors, which makes this a common problem. Memory complaint is associated with poorer performance in all the cognitive domains identified with validated instruments, mainly in relation to immediate recall, verbal fluency, and processing speed. These results have been described not only in older adults with increased memory complaints (cognitively intact), but also in those with cognitive impairment (^{Brailean et al., 2019}). We found a higher frequency of SMC than that reported, interestingly, we observed that most of the participants with worse performance in daily cognition had higher SMC, despite having similar sociodemographic characteristics, it stands out that the greatest complaint is found in the items related in memory domain. E-Cog has been proposed as an instrument to assess subjective cognitive decline (SCD): Any occasion SCD = any item scored ≥ 2, but none ≥ 3; any consistent SCD = any item scored ≥ 3. (^{Rueda et al., 2015}) That is, the prognostic value of SCD for incident MCI improves when both consistency of SCD and associated concern are evaluated.(^{van Harten et al., 2018}) Thus, it is important to highlight the role of loneliness and isolation in SMC.