geriatrics Review The Challenge of Subjective Cognitive Complaints and Executive Functions in Middle-Aged Adults as a Preclinical Stage of Dementia: A Systematic Review Felipe Webster-Cordero 1,2, * and Lydia Giménez-Llort 1,3, * 1 Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, E-08193 Barcelona, Spain 2 Hospital Santa Inés, Cuenca 010107, Ecuador 3 Institut de Neurociències, Universitat Autònoma de Barcelona, E-08193 Barcelona, Spain * Correspondence: felipe.webster@autonoma.cat (F.W.-C.); lidia.gimenez@uab.cat (L.G.-L.); Tel.: +593-98-488-4724 (F.W.-C.); +34-93-5812378 (L.G.-L.) Abstract: Subjective cognitive complaints correspond to a heterogeneous construct that frequently occurs in the early stages of older adult life. Despite being a common source of worry for middle-aged people, it can be underestimated when clinical and neuropsychological assessments discard any un- derlying pathological processes. Negative age stereotyping but also self-stereotyping can contribute to doing so. Although its diagnosis is a challenge, its implication as a possible predictor of mild cognitive impairment or dementia increases the interest in its early diagnosis and intervention. The present systematic review analyzes the empirical data on the relationship between these complaints and early executive dysfunction with possible predictive value for preclinical stages of dementia. The sixteen papers obtained from the PubMed and Embase databases were exploratory, cross-sectional  and prospective in scope. The studies corroborated the relationship between subjective cognitive  complaints and some executive processes, which is noteworthy since many people with subjective Citation: Webster-Cordero, F.; executive complaints progress to dementia. The relational studies confirmed that impaired executive Giménez-Llort, L. The Challenge of Subjective Cognitive Complaints and performance is associated with CSF biomarkers and reduced cortical volume in specific brain regions. Executive Functions in Middle-Aged However, the heterogeneity of reports in these studies demands stronger efforts in future research Adults as a Preclinical Stage of with specific tools applied in clinical and neuropsychological assessments and analyzed under a Dementia: A Systematic Review. gender perspective. Geriatrics 2022, 7, 30. https://doi.org/ 10.3390/geriatrics7020030 Keywords: subjective cognitive complaints; stereotypes; aging; complaints; executive functions; Academic Editor: Phyo Kyaw Myint memory; mild cognitive impairment; dementia Received: 7 February 2022 Accepted: 4 March 2022 Published: 8 March 2022 1. Introduction Publisher’s Note: MDPI stays neutral With the aging population, geriatricians highlight the relevance of disease prevention with regard to jurisdictional claims in and diagnosis of old-age-specific diseases and the best use of healthcare professionals’ published maps and institutional affil- specialties [1]. However, in this context, age stereotypes are known to influence behavioral, iations. physical and cognitive outcomes among healthy older adults [2–4]. Moreover, the health care professionals’ beliefs and attitudes toward older people may also exert a significant impact [5]. Thus, stigmatization of older people has been shown to induce the overestima- tion of their age-related cognitive decline and the common perception that older people Copyright: © 2022 by the authors. have worse cognitive competencies [2]. Growing evidence shows that these negative aging Licensee MDPI, Basel, Switzerland. stereotypes impair the performance of healthy older adults on cognitive tests, while positive This article is an open access article distributed under the terms and age stereotyping exerts less intense effects [2]. Thus, the impact of the age-based stereotype conditions of the Creative Commons threat (the threat of being judged stereotypically) on older adults’ episodic and working Attribution (CC BY) license (https:// memory, false memory susceptibility and subjective age has been recently reported [6–10]. creativecommons.org/licenses/by/ Research on the role of age stereotypes and subjective aging in health across the life 4.0/). span identifies several theoretical approaches for potential mechanisms to explain how Geriatrics 2022, 7, 30. https://doi.org/10.3390/geriatrics7020030 https://www.mdpi.com/journal/geriatrics Geriatrics 2022, 7, 30 2 of 14 personal views of aging might influence health-related outcomes in later life [11]. In fact, self-stereotyping also has long-term negative effects. According to the internalization hypothesis, holding more negative age stereotypes and perceiving more age discrimina- tion are associated with feeling older, lower self-esteem and worse perceptions of one’s own aging [7]. Similarly, internalized negative age stereotypes and subjective cognitive impairment have been related to increased depressive effects despite not being related to age-related dysregulations of cortisol [12]. In contrast, essentialist beliefs about aging seem to moderate the impact of negative age stereotypes on older adults’ performance and physiological reactivity [13]. Despite most research on age stereotypes being focused on the above-mentioned exter- nal/internal distortions referred to the older adult, nihilist aptitudes towards the inherent limitations of advanced aging and underestimations during middle adulthood can also occur [5]. Gerontologists warn that negative aging stereotypes can decrease performance on short cognitive tests widely used in primary care to screen for predementia [14]. However, on the other hand, the cognitive decline that occurs after the age of 50 or 60 is accompanied by minimal changes in some cognitive processes that are, in many cases, self-perceived by the individual but yet undetectable by classical neuropsychological assessments primarily focused on declarative memory. Hence, the term subjective cognitive impairment (SCI) associated with a subjective decline in one or more cognitive areas (attention, memory, reasoning, language, etc.) is not objectively measurable after a neurocognitive assessment despite being reported by the subject or a close person [15]. Its possible relationship with dementia points to this challenging SCI diagnosis and understanding as a subject of grow- ing research interest, since it could have a crucial role in applying early and personalized preventive and therapeutic interventions [16,17]. An increasing number of young adults calls at clinical centers for clinical consulta- tion due to problems in their cognitive performance, reporting problems with memory, concentration, or reasoning. In the case of middle-aged adults, this awareness usually becomes a source of worry about a predictive value for a worse clinical condition, a pre- lude to dementia. People’s subjective perception of their cognitive performance is highly variable and the heterogeneity of these subjective cognitive complaints makes differential diagnosis a challenge [18,19]. In fact, cognitive symptomatology in adults may be directly related to depressive symptoms or personality characteristics that influence their perception of their cognitive performance [20,21]. Moreover, the sum of these factors may be a predictor of a negative perception of quality of life [22]. Therefore, in many cases, neuropsychological assess- ment discards the existence of an actual cognitive impairment underlying the subjective complaints [23]. In the current pandemic scenario, the number of middle-aged adults with cognitive complaints has increased dramatically, becoming a topic of growing inter- est [24,25]. This subclinical condition has been usually exclusively associated with loss of memory processes, perhaps due to the lack of specificity when assessing neurocognitive processes. In this sense, questionnaires or standardized tests to assess subjective memory complaints are not analyzed in detail; many of them do not assess all the cognitive pro- cesses involved or do not assess qualitative aspects, via which clinically significant data are obtained [26,27]. Due to the significant heterogeneity of the neurocognitive processes involved in sub- jective cognitive impairment, the neuropsychological assessment is an essential diagnostic tool together with the multi- and interdisciplinary clinical study [28]. There are conflict- ing data on how this symptomatology manifests and whether it can be determined as a syndrome distinct from mild cognitive impairment (MCI) and dementia [29]. However, although there is not a unified criterion for this entity yet, biomarkers and evidence of anato-functional changes through neuroimaging studies are now known [30,31]. Regarding the dysfunctional neuroanatomical substrate, frontal executive processes seem to be, in part, the target of several lines of research where they are analyzed as possible initial symp- toms of this not yet determined complex clinical picture. Therefore, the present review Geriatrics 2022, 7, x FOR PEER REVIEW 3 of 16 Geriatrics 2022, 7, 30 3 of 14 the target of several lines of research where they are analyzed as possible initial symptoms of this not yet determined complex clinical picture. Therefore, the present review aims to systematically analyze the emerging empirical data on the relationship between subjective aims to systematically cognitive analyze complaints (SCCs) andthe emerging executive empirical functions in data on the relationship middle-aged between adults to help un- derstand possible deficits at this level in the preclinical stages of dementia. This wouldto subjective cognitive complaints (SCCs) and executive functions in middle-aged adults help understand possible deficits at this level in the preclinical stages of dementia. This also provide evidence to counteract the underestimation of SCCs before clinical diagnosis would also provide evidence to counteract the underestimation of SCCs before clinical using the biomedical model. diagnosis using the biomedical model. 2.2.Materials Materialsand andMethods Methods InInthe present study, the present a systematic study, review a systematic on the review onrelationship between the relationship subjective between cog- subjective nitive complaints and executive functions was carried out, following the guidelines cognitive complaints and executive functions was carried out, following the guidelines of theof PRISMA [32] method for its correct elaboration (see Figure 1). the PRISMA [32] method for its correct elaboration (see Figure 1). Figure 1. Flow chart of the systematic review on subjective cognitive complaints and executive functions. Figure 1. Flow chart of the systematic review on subjective cognitive complaints and executive func- tions. 2.1. Systematic Search (Databases, Descriptors, Search Formulas) Through the systematic search, scientific publications from 2005 (when the literature on 2.1. Systematic Search (Databases, Descriptors, Search Formulas) “subjective complaints” started to grow) to the present on the chosen topic were analyzed, usingThrough the systematic the PubMed search, and Embase scientificas databases publications the primaryfrom 2005 tool. The(when termsthe literature “subjective”, on“memory”, “cognitive”, “complaints”, “executive functions” and “working memory”ana- “subjective complaints” started to grow) to the present on the chosen topic were used lyzed, in theusing searchthe PubMed with and Embase the Booleans “AND”databases and “OR”asyielded the primary tool. as 890 results The terms sources possible “subjec-of tive”, “memory”, analysis, after which“cognitive”, “complaints”, inclusion and “executive exclusion criteria functions” and “working were established. memory” used in the search with the Booleans “AND” and “OR” yielded 890 results as 2.2. Inclusion possible sourcesCriteria of analysis, after which inclusion and exclusion criteria were established. 1. Empirical research on the relationship between subjective cognitive complaints and executive functions in preclinical stages of dementia; 2. Papers published from 2005 to the present and with a study population specificity of 60 years of age and older. Geriatrics 2022, 7, 30 4 of 14 2.3. Exclusion Criteria 3. Papers addressing the topic of subjective cognitive complaints in a general or specific way in other clinical contexts; 4. Studies analyzing executive functions in stages where there is already a diagnosis of dementia in advanced stages. 2.4. Flow Chart Following these criteria, on reading the title of the initially selected articles, 51 papers were chosen. After reading the abstract, 35 were discarded; some focused on global cognitive processes and not specifically executive ones (n = 12) and others studied the relationship between subjective cognitive complaints and executive functions in other clinical contexts (n = 23). Finally, 16 articles were selected for review, as they focused on studying the relationship between some executive processes with SCCs and their involvement in the subclinical stages of mild cognitive impairment and dementia. 3. Results Table 1 summarizes the empirical studies and depicts the main findings on the rela- tionship between subjective cognitive complaints and executive functions. The number of studies on the relationship between subjective cognitive complaints and executive functions was scarce, but the overall data are based on a total sample of 5137 participants gathered from western (USA, Australia, and Central and Southern Eu- rope) and oriental (Korea) countries. The sociodemographic variables included sex (with a 1:3 Women:Men ratio) and years of education, but none analyzed the data on subjective complaints in a segregated manner. All the studies confirmed the hypothesis of a direct link between these two psychological constructs, providing evidence at the neuropsychological but also neuroimaging and biomarker levels. Geriatrics 2022, 7, 30 5 of 14 Table 1. Summary of the studies analyzing the relationship between subjective cognitive complaints and executive functions. Authors Sample Methodology Results 187 participants (83 W and 84 M): 15 cases who developed AD (7 W and 8 M) Longitudinal study (4 years) Mean age: 86.17 years NEUROPSYCHOLOGY In total, 15 participants developed Rapp and Reischies (2005) [33] Mean years of education: 11.43 MMSE, TMT part B, Digit Symbol Substitution Test, Digit Alzheimer’s disease at 4 years (scoring low 172 cases who did not develop AD (76 W and 76 M) Letter test, on all follow-up assessments). Mean age: 79.08 years Identical Pictures Mean years of education: 11.30 Country: Germany 87 participants (54 W and 33 M): 30 HC subjects (21 W and 9 M) Mean age: 72 years Mean years of education: 17 The participants with MCI and SCCs reported 28 SCC subjects (20 W and 8 M) NEUROPSYCHOLOGY significant difficulties with selective aspects Rabin et al. (2006) [34] Mean age: 74 years MMSE, CVLT-II, DRS-2, WCST, D-KEFS, of executive functioning (working memory). Mean years of education: 16 WMS-III, BRIEF-A In addition, it was more likely that their 29 MCI subjects (13 W and 16 M) informants reported the same difficulties. Mean age: 74 Mean years of education: 16 Country: United States The decline in the cognitive performance in 92 subjects with incident AD NEUROPSYCHOLOGY episodic memory tests accelerated 7 years assessed for 15 years prior to diagnosis Memory (Free Recall on the Free and Cued Selective prior to diagnosis; this was 2–3 years for (48 W and 44 M) Reminding Test), Grober et al. (2008) [35] executive-function performance (associated Mean age: 79.8 years executive functions (categorical fluency, letter and with pathological signs in the frontal circuits), Mean years of education: 16.5 path fluency), while verbal-intelligence performance Country: United States, Netherlands and verbal intelligence (AMNART) declined in the vicinity of diagnosis. 131 subjects (68 W and 63 M): 25 HC subjects Mean age: 69 years Mean years of education: 13.5 32 subjective MCI NEUROPSYCHOLOGY Mean age: 71 years Wechsler Test of Adult Reading (WTAR); Both the amnestic-MCI and subjective-MCI Mean years of education: 13 estimated full-scale intelligence quotient (FSIQ); Boston Saunders and Summers (2010) [36] groups displayed impaired attentional 60 amnestic MCI Naming Test (BNT); processing and working-memory capacity. Mean age: 71 years Rey Auditory Verbal Learning Test (RAVLT); Mean years of education: 13.1 Paired AssociateLearning (PAL). 14 mild AD Mean age: 76 years Mean years of education: 12 Country: Australia Geriatrics 2022, 7, 30 6 of 14 Table 1. Cont. Authors Sample Methodology Results Patients meeting preclinical AD criteria NEUROPSYCHOLOGY showed deterioration of memory, executive 132 participants with SCCs (56 W and 76 M) Neuropsychological assessments with 1–2 years functions and global cognition over time, Mean age: 61.4 years follow-up (MMSE) van Harten et al. (2013) [37] associated with evidence of CSF. Mean years of education: 6 CSF BIOMARKERS MMSE total scores, delayed recall and Country: Netherlands CSF biomarker data on β-amyloid, initiation/perseveration subscales were total tau, hyperphosphorylated tau-181 significantly lower than the control group. 522 subjects (253 W and 269 M): 307 CN subjects (138 W and 169 M) Mean age: 73.9 years CSF BIOMARKERS 71 subjects with SCCs (25 W and 46 M) Conversion from executive SCI to Analysis of CSF biomarker data Mean age: 71.6 years MCI/dementia of 50% at 7 years. NEUROIMAGING 51 subjects with executive SCI (21 W and 30 M) Participants with SCCs showed atrophy of Toledo et al. (2015) [38] Hippocampal volume measurements and Mean age: 77.3 years orbital prefrontal regions and higher p-tau MRI-SPARE-AD values 66 subjects with memory SCI (49 W and 17 M) and RM-SPARE-EA values (indicative of Hypometabolic convergence index Mean age: 75 years pathological changes). Posterior cingulate metabolic rate for glucose 27 subjects with multi-domain SCI (20 W and 7 M) Mean age: 78 years Country: United States 265 participants (178 W and 79 M): 188 CN subjects (120 W and 60 M) Mean age: 71.94 years Significantly lower pre-DCL-group scores in Mean years of education: 9.69 NEUROPSYCHOLOGY visual memory and executive functions, with Seo et al. (2016) [39] 77 subjects with pre-DCL MMSE; categorical and phonemic fluency tests, Stroop poor performance in inhibition and (58 W and 19 M) test, path test and TMT A–B goal-directed behavior. Mean age: 72.64 years Mean years of education: 9.64 Country: Korea A total of 16% of participants showed progression to MCI and AD at the 2–3 year follow-up. NEUROPSYCHOLOGY 238 participants with SCI (109 W and 129 M) Reduced fronto-temporo-parietal cortical Neuropsychological assessment (MMSE) Verfaillie et al. (2016) [40] Mean age: 62 years thickness associated with reduced NEUROIMAGING Country: Netherlands memory performance. Measurement of cortical thickness by MRI Reduced temporal cortical thickness was associated with decreased executive performance. Geriatrics 2022, 7, 30 7 of 14 Table 1. Cont. Authors Sample Methodology Results 55 participants (35 W and 20 M): 23 subjects with mild AD (9 W and 14 M) Mean age: 73.95 years NEUROPSYCHOLOGY Participants with mild AD and their Mean years of education: 15.56 Fogarty et al. (2017) [41] Application of the BRIEF-A to participants and informants informants reported greater difficulties in 32 adult control subjects (26 W and 6 M) (spouse/child) most of the clinical scales assessed. Mean age: 69.84 years Mean years of education: 13.96 Country: England NEUROPSYCHOLOGY 1442 participants MMSE, Participants with SCCs performed worse on 1088 HC subjects Bae et al. (2017) [42] initiation/perseveration (IP), Subscale of the Korean all cognitive tests that evaluated memory and 354 with SCCs version of Mattis Dementia executive functions. Country: South Korea Rating Scale (K-DRS) Patients and informants were more likely to NEUROPSYCHOLOGY 83 participants (51 W and 32 M): report executive problems in working MMSE and Weschler Memory Scale, Geriatric Depression 35 adults with SCI (22 W and 13 M) memory, planning/organising and Scale, Beck Depression Inventory II Mean age: 68.5 years monitoring. and Big Five Inventory Viviano et al. (2018) [43] 48 adults without SCI Subjective cognitive impairment was NEUROIMAGING (29 W and 19 M) associated with lower functional connectivity Assessment of functional connectivity of brain regions Mean age: 67.08 years in retrosplenial–precuneus regions and using MRI and Country: United States, Netherlands memory-system regions (poorer performance diffusion of regions in visual working memory). Neuropsychological follow-up for 1 year 68 normal subjects (46 W and 22 M): NEUROPSYCHOLOGY Pre-AD subjects showed significantly higher 52 HC (33 W and 19 M) Subjective Cognitive Complaints Questionnaire (SCI-Q) scores with respect to language, attention and Mean age: 63.87 years MMSE, Memory Alteration Test, Boston Naming Test, executive decline, confirmed by their Mean years of education: 11.96 Valech et al. (2018) [44] comprehension of commands (BDAE), incomplete letters informants. 16 pre-AD (13 W and 3 M) and number location (VOSP), TMT-A, phonetic fluencies Significantly decreased cognitive Mean age: 66.5 years (FAS), Free and Cued Selective Reminding Test performance in pre-AD on tests of inhibition Mean years of education: 9.56 (FHCRT-IR), semantic fluency test (animals), Stroop test and semantic fluency. Country: Spain Hospital Anxiety and Depression Scale NEUROPSYCHOLOGY Significant association between β-amyloid TMT A-B, rule shift card subtest (BADS), automatic deposition and low executive performance in 195 participants with SCD (121 W and 74 M) inhibition subtest (AI-SKT), digits (WAIS-III), letter, automatic inhibition Mean age: 65.71 years semantic and verbal fluency tests Pérez et al. (2020) [45] (AI-SKT). Mean years of education: 14.94 NEUROIMAGING Low executive performance was associated Country: Spain Functional neuroimaging studies (positron emission with lower volume in bilateral hippocampal tomography with 18F-Florbetaben and MRI) and left frontal regions. Analysis of gray matter volume Geriatrics 2022, 7, 30 8 of 14 Table 1. Cont. Authors Sample Methodology Results 1442 participants (886 W and 556 M) NEUROPSYCHOLOGY (age: ≥65 years): Significant relationship between depression Mini-Mental State Examination, Korean version 1088 HC subjects (642 W and 446 M) and SCCs. (MMSE-KC)—use of the recording and retrieval subscales Kim et al. (2020) [46] Mean years of education: 5.66 Lower performance in global cognition, for memory assessment and the initiation/perseveration 354 SCC subjects (244 W and 110 M) memory and executive functions (verbal subscales (Korean rating scale K-DRS) to assess Mean years of education: 3.33 fluency) in the study group. executive functions Country: Korea 62 subjects: 17 SCC subjects The older SCC subjects faced problems in NEUROPSYCHOLOGY Esmaeili et al. (2021) [47] 30 amnestic-MCI subjects maintaining alertness to external stimuli Attention Network Test (ANT) 15 HC subjects (attention-processing problems). Country: Iran 136 subjects (67 W and 59 M): 28 young adults with SCCs (17 W and 11 M) Mean age: 21 years NEUROPSYCHOLOGY 37 young adults without SCCs (16 W and 11 M) The older adults with SCCs presented deficits Iowa gambling task (IGT) Mean age: 23 years in the decision-making process. These data Garrido et al. (2021) [48] NEUROLOGY 32 older adults with SCCs (18 W and 14 M) were also observed in the neuronal Electroencephalogram (EEG) Mean age: 63 years mechanisms studied. Feedback-related negativity (FRN) 39 older adults without SCCs (16 W and 23 M) Mean age: 65 years Country: Spain Abbreviations: W, women; M, men; SCCs, subjective cognitive complaints; SCD, subjective cognitive decline; AD, Alzheimer’s disease; HC, healthy control; CSF, cerebrospinal fluid; CN, cognitively normal; SCI, subtle cognitive impairment; MRI-SPARE-AD, spatial pattern abnormalities for early Alzheimer’s recognition; MRI, magnetic resonance imaging; MCI, mild cognitive impairment. Geriatrics 2022, 7, 30 9 of 14 The experimental designs included cross-sectional analyses to describe the executive performance of the studied population at a given time. In addition, a few longitudinal follow-up and prospective analyses were conducted. The descriptive studies corroborated the existence of a direct relationship between subjective cognitive complaints and the impairment of several executive processes, such as attention, working memory, initiative, cognitive flexibility, inhibition, planning, monitoring, verbal fluency, decision making and goal-directed behaviors [36,39,42,45–48]. These functions were directly associated with self- reported complaints from participants but also their informants [34,41,43,44]. On the other hand, the characterization of executive performance throughout the evolution of cognitive deterioration, based on cognitive complaints before or after clinical diagnosis, pointed to follow-up studies as essential not only to diagnose and monitor cognitive impairment but, more importantly, to determine a possible predictive relationship with subjective cognitive complaints. Thus, the longitudinal studies [33,35,37,38,40,44] indicated that, in a variable percentage, people presenting subjective cognitive complaints showed a significant cognitive decline in executive processes during the progressive neuropsychological follow- ups, evolving to a possible picture of mild cognitive impairment (MCI) or dementia. In addition, a 15-year prospective study on people with Alzheimer’s disease showed that lower cognitive performance at the executive level started to become more pronounced 2–3 years prior to receiving a clinical diagnosis [35]. The application of standardized neuropsychological tests was the common tool in all the studies, with MMSE as a general screening tool to assess cognitive performance being used in seven of them. However, the review shows that the administration of classical screening tests or questionnaires to study cognitive impairment may not be sufficient for a detailed understanding of executive performance since they are not sensitive enough. Thus, inserting specific neuropsychological tools for executive functions is essential in any clinical analysis. Among them, the most used tests assessed verbal and semantic fluency, cognitive processes such as working memory (digits—WAIS), attentional control (digits, symbol- substitution test and TMT A–B), initiation/perseveration (Korean rating scale K-DRS), BRIEF-A and inhibitory control (Stroop test). On the other hand, not all but some of the studies complemented the neuropsychological assessment with biological markers in the CSF or the use of neuroimaging [37,38,40,43,45,48]. Despite the high cost of neuroimaging studies and their limitations in terms of specificity and power resolution in the initial clinical analysis, which limits their applicability in the population with subjective cognitive complaints, the studies related executive performance to the presence of biomarkers in the CSF and to reductions detected by regional volumetric analyses. Interestingly, a direct relationship between CSF biomarkers present in the preclinical stages of dementia and the impairment of executive processes was found. Thus, higher p-tau values and β-amyloid deposition were associated with subjective cognitive complaints and lower performance in executive functions such as inhibition [37,38,45]. Similarly, neuroimaging studies revealed a direct relationship between subjective cognitive complaints and atrophy of orbital prefrontal regions, reduced functional connectivity in retrosplenial–precuneus regions, reduced temporal cortical thickness (bilateral hippocampi) and left frontal regions, associated with decreased executive performance [38,40,43,45]. 4. Discussion The first observation of this systematic review is that, despite the scarcity of literature focusing on the early study of cognitive decline in executive processes, there is a recent growing interest in the prodromal stages of this cognitive domain and the potential predic- tive value of subjective complaints in this respect. The data corroborate the relationship among subjective cognitive impairment and executive functioning, the relevance of not underestimating the patients’ and/or informants’ complaint reports. However, the data can be considered inconclusive, a fact that may be due to the rather small number of SCI patients used in most of the studies, as well as the heterogeneity of the neuropsychological tools used and multiple variables involved. Consistency regarding the screening tools is Geriatrics 2022, 7, 30 10 of 14 needed. Complementing neuropsychological screening with biomarkers and neuroimaging was presented as critical to confirm the early changes in neurological substrates poten- tially underlying the subjective complaints. Still, despite the complexity of the studies with biomarkers, some studies used almost only MMSE, a test with global acceptance but without the necessary specificity and sensitivity to assess SCI or even MCI patients. The need for further research and guidelines is enhanced in the current aging popu- lation [1] and the global health situation, where the number of middle-aged people with cognitive complaints has dramatically increased [24,25]. The most recent work, a systematic review on the relationship between subjective cognitive complaints and informants’ reports, by Wasef et al. [49] in the context of anesthesiology, provides a general description of the number of cognitive domains affected, with executive functions figuring among them. Studies assessing executive characteristics in patients with a defined diagnosis, an- alyzing their impact on a possible prognosis, were more common. For instance, people with amnestic mild cognitive impairment (aMCI) exhibiting frontal executive dysfunc- tion at baseline had overall cortical thinning, including frontal areas, and a higher risk of dementia conversion than those exhibiting visuospatial or language dysfunction [50]. In that clinical scenario, confirming this poor prognosis was essential to determine the higher priority of this subgroup for intervention therapy among aMCI patients. Similarly, proper consideration of the reliability and possible predictive value of subjective cognitive complaints and a better understanding of the early stages of cognitive decline in executive functions would help to define timely interventions in a population that may be at risk. In this sense, comprehensive educational group interventions in community-dwelling older women reporting normal age-related cognitive complaints in the absence of actual cognitive decline were shown to be effective [51]. Complainers receiving psycho-education about cognitive aging and contextual factors, including health, lifestyle, beliefs and negative age stereotypes, reported significatively fewer negative emotional reactions towards cognitive functioning, considered by the authors as a prerequisite for improved subjective cognitive functioning and wellbeing. Studies analyzing the need to include tools (self-reports) that assess more executive processes such as working memory rather than declarative memory processes also ad- vocated for the relevance of multiple-cognitive-domain screening compared to classical unidimensional cognitive assessments [52]. Thus, one of the limitations in the analyzed studies was the generalization in neurocognitive assessments. Despite the use of more-or- less-specific tests for executive functioning, the study of memory as a unitary process and predictor of dementia continued to be prioritized. However, authors such as Giovanello and Verfaille [53] considered the need to study memory as a multimodal process related to other cognitive functions, making it possible to analyze the relationship of this process with cognitive impairment in-depth. In this sense, the study of specific memory modal- ities would be associated with executive processes and the activation of frontal regions, which could be associated with preclinical stages of dementia. Types of memory such as prospective memory and metamemory associated with self-awareness of illness are processes that have been investigated in recent years concerning cognitive complaints and executive functioning, as they share a common anato-functional niches, such as the prefrontal cortex [54–57]. In the same vein, self-reports and reports from external informants can work as sen- tinels providing valuable information about executive functioning at preclinical stages. Fogarty (2017) [41] stated that people with mild AD had more significant concerns re- garding their executive functions associated with their daily lives, an opinion which was corroborated, to a lesser extent, by their informants. However, other studies indicated that only self-reported cognitive complaints predicted future cognitive changes and were associated with executive functioning, unlike informants’ reports being associated with other cognitive processes [58,59]. Highly heterogeneous variables influence subjective cognitive complaints, contribut- ing to underestimating the reliability of this psychological construct. Emotional factors and Geriatrics 2022, 7, 30 11 of 14 affective disorders, including depression and anxiety, negatively influence memory but also executive performance. To monitor their contribution, some of the revised studies included neuropsychiatric symptoms in clinical assessments [60,61]. In addition, personality factors can directly influence the self-perception of everyday failures, which could be associated with executive problems [62]. Still, none of the revised works on subjective cognitive com- plaints and executive functions considered nor assessed the contribution of age stereotypes. In fact, only a few research reports in the literature have specifically studied subjective cognitive complaints and age stereotypes [12,63]. Lubitz et al. [63] recently developed and assessed the psychometric properties of a new questionnaire on subjective cognitive complaints in multiple cognitive domains, its association with psychological variables and the distinction of complainer types. Their study confirmed the strong influence of depressiveness on the overall level of subjective cognitive complaints. Most importantly, it detected that people with complaints about executive functions exhibited the highest levels of affective disorders, were younger and had less social integration. Depressive symptoms and memory impairments are associated with heightened stress hormone levels during aging; conversely, long-term exposure to high endogenous levels of glucocorticoids is associated with both memory impairment and smaller hippocampal volume. In this context, Sindi et al. [12] studied the role of internalized negative aging perceptions and found them to be associated with increased depressive symptoms and subjective—but not objective—memory complaints. Interestingly, negative age stereotypes did not predict increased cortisol levels, suggesting that the mechanism underlying the association between stereotypes and cognitive impairments may be independent of age- related dysregulations of cortisol secretion [12]. However, although depression and stress contribute to cognitive performance, almost none of the studies used as an obligatory criterion the absence of psychiatric comorbidity. The studies analyzed in the present review did not provide conclusive data about the relationship among sociodemographic variables, such as gender and level of education, that may influence the individual’s subjective perceptions and executive impairment. Neverthe- less, gender medicine considers essential to analyze the effects of sex and gender [64,65] and a recent research study found significant differences in executive performance between men and women with subjective cognitive complaints, with men performing worse than women [66]. On the other hand, in the study, there was minimal specificity of participants’ level of education and its relationship as a possible predictor of dementia. In this sense, we recently confirmed the relevance of considering the interactions between sex/gender and education factors, since a lower level of education in women can be a critical risk factor for dementia in vulnerable subjects [67]. 5. Conclusions In conclusion, the study of subjective cognitive complaints and their relation to execu- tive functioning draws attention to several dimensions of clinical interest; therefore, it can be foreseen to be a promising emerging field. However, the specific search for information in this regard will find limitations as long as the term “subjective cognitive complaints” remains ambiguous and does not have a precise definition. Psychiatric comorbidity should be considered as a confounding factor, thus an exclusion criterion. Studies including a rather small number of SCI patients, no consistency regarding tools and the general use of MMSE are other limitations of the current literature. The studies corroborated the relationship between subjective cognitive complaints and some executive processes, which is noteworthy since many people with subjective executive complaints progress to dementia. The relational studies confirmed that impaired executive performance was associated with CSF biomarkers and reduced cortical volume in specific brain regions. However, it is necessary to focus on unifying the screening tools based on processes rather than isolated functions when studying the significant heterogeneity involved in this preclinical construct. Applying an adequate neuropsychological assessment in parallel to the clinical study and a detailed analysis of sociodemographic variables Geriatrics 2022, 7, 30 12 of 14 would allow a better definition of the neurocognitive profile of adults who report executive complaints in their daily lives to be obtained. Otherwise, there is a risk of underestimating the reliability and predictive value of self-reporting, which may hamper the chances of providing an adequate diagnosis and early and timely intervention. Author Contributions: Conceptualization, F.W.-C. and L.G.-L.; methodology, F.W.-C.; writing— original draft preparation, F.W.-C.; writing—review and editing, F.W.-C. and L.G.-L.; supervision, L.G.-L.; funding acquisition, L.G.-L. All authors have read and agreed to the published version of the manuscript. Funding: Memorial Mercedes Llort Sender 2021/80/09241941.5. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Not applicable. Conflicts of Interest: The authors declare no conflict of interest. References 1. Arai, H.; Ouchi, Y.; Yokode, M.; Ito, H.; Uematsu, H.; Eto, F.; Oshima, S.; Ota, K.; Saito, Y.; Sasaki, H.; et al. Members of Subcommittee for Aging. Toward the realization of a better aged society: Messages from gerontology and geriatrics. Geriatr. Gerontol. Int. 2012, 12, 16–22. [CrossRef] 2. Marquet, M.; Missotten, P.; Adam, S. 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