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Frequency, sociodemographic, and neuropsychological features of patients with subjective cognitive decline diagnosed using different neuropsychological criteria

Alzheimer's Research & Therapy volume 16, Article number: 261 (2024) Cite this article

Abstract

Background

Subjective Cognitive Decline (SCD) is recognized as a risk stage for future cognitive impairment and dementia. The criteria for SCD include normal performance on neuropsychological testing; however, there is a lack of consensus regarding standard score cut-offs for neuropsychological tests to define cognitive impairment and to differentiate between SCD and Mild Cognitive Impairment (MCI). This study aimed to assess the frequency of SCD diagnosis using various neuropsychological definitions of cognitive normality and to characterize the sociodemographic and neuropsychological features of SCD patients diagnosed under these criteria.

Methods

The Cognitive Complaints Cohort (CCC) participants were diagnosed following Subjective Cognitive Decline Initiative (SCD-I) criteria. Normal cognitive performance was defined by the absence of Mild Cognitive Impairment (MCI) according to the five sets of MCI neuropsychologically based criteria defined by Jak and Bondi. Descriptive statistics were used to analyze sociodemographic, clinical, and neuropsychological data. A bootstrap methodology was employed to estimate the mean and 95% confidence intervals (CI) for specific parameters of interest, namely the SMC scale (subjective memory complaints scale), Mini-Mental State Examination (MMSE), Blessed Dementia Rating Scale – first part (BDRS first part), and Geriatric Depression Scale (GDS).

Results

Among the 1268 subjects included, the prevalence of SCD diagnosis exhibited substantial variation across SCD-I criteria using different neuropsychological definitions of cognitive normality (ranging from 16.4 to 81.3%). When using the most conservative criteria to define cognitive impairment (2 tests within a cognitive domain > 1.5 SD below age-adjusted means), the resulting Conservative SCD group had poorer global cognitive function (MMSE: mean 27.15, 95% CI 27.00-27.31), whereas when using the most liberal criteria to define cognitive impairment (only one test > 1 SD below age-adjusted means) the resulting Liberal SCD group had superior performance in daily-life functioning (BDRS first part: mean 0.30, 95% CI 0.23–0.38). However, subjective cognitive complaints and neuropsychiatric symptoms did not significantly differ among SCD diagnostic groups.

Conclusions

The utilization of diagnostic criteria using distinct neuropsychological definitions of cognitive normality significantly impacts the frequency of SCD diagnosis and characterizes different patient populations. Consequently, it is essential to specify the criterion when diagnosing a SCD patient and to understand the risks and benefits of using different criteria to define cognitive impairment.

Background

Over 55 million people worldwide presently have dementia, and it is estimated that this number will rise to 139 million people by 2050 [1]. It is well known that in the most common dementing neurodegenerative disorders, namely Alzheimer’s disease, clinical symptoms develop only after a long period of silent progressive brain damage [2].

Initially, the concept of mild cognitive impairment (MCI) emerged with the primary goal of identifying early cases of memory impairment typical of Alzheimer’s disease [3]. MCI was later more broadly defined by the presence of cognitive complaints raised by the patient or an informant associated with an objective cognitive impairment in one or more cognitive domains, with preservation of functional independence and no dementia [4]. The significance of the MCI concept lies in its pivotal role in establishing an elevated risk for dementia [4], [5]. Theoretically, by defining MCI, patients could be objectively diagnosed at an early stage of cognitive impairment, when interventions might prove more productive than at later stages [6]. However, before demonstrable cognitive impairment, patients may have experienced a subjective decline in memory or other cognitive domains [6]. There was no unified concept for this stage, with various ideas and terminologies employed in studies involving this patient population [7]. This limited the ability to compare and aggregate the findings obtained [7]. Additionally, the identification of patients for whom subjective complaints correspond to preclinical neurodegenerative disorders might prove challenging since many different physical and mental conditions can influence self-experienced cognitive fitness in the elderly. Subjective cognitive complaints are closely correlated with symptoms of depression [8,9,10], and anxiety [8], even subclinical [11]. Regarding personality traits, subjective cognitive complaints appear to be more common in patients with higher levels of neuroticism [8, 12] and inversely related to traits like openness and conscientiousness [8]. Age [9] and physical health problems [12] are also associated with higher subjective cognitive complaints.

Due to such heterogeneity, it became evident that a consensus on the terminology and research criteria was crucial to accurately study this important group of patients and generate comparability across studies. Thus, the Subjective Cognitive Decline Initiative (SCD-I) was created in 2012 to help develop a common research framework to characterize SCD [13]. SCD was then defined as a self-estimated decline in cognitive capacity compared to the individual’s previous level of functioning, which neuropsychological tests, and basic criteria cannot confirm were developed to create an operationalized definition (Table 1).

Table 1 SCD basic criteria according to SCD-I [13]
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However, despite the vital contribution of these criteria to the study of this population, the SCD concept still faces relevant challenges, mainly related to operationalization problems that limit the comparability and the generalizability of the clinical findings. There is neither a universally accepted neuropsychological test nor a self or observer/informant scale to classify an individual as having SCD. Furthermore, no standard cut-offs in neuropsychological instruments are consensual to define cognitive impairment and to differentiate between SCD and MCI [14]. Both entities involve the presence of cognitive complaints. Still, SCD requires normal cognition, and MCI entails impaired cognition, so the way neuropsychological tests define normality establishes in practical terms the boundary between these two entities [15]. To our knowledge, studies have yet to compare various commonly used neuropsychological definitions of cognitive normality for distinguishing between SCD and MCI. Concerning the diagnosis of MCI utilizing objective neuropsychological cut-offs, the Jak-Bondi criteria, formulated in 2009, stand as a significant milestone [16]. These criteria introduced a more comprehensive approach to MCI diagnosis. The authors achieved this by refining the operationalization of diagnosis by including a broader spectrum of cognitive domains, utilizing multiple tests within each domain, and adjusting commonly employed cut-off scores to define impairment. They found differences in MCI diagnosis depending on the classification criteria employed, and suggested that the “Comprehensive criteria” (2 tests within a domain > 1SD below adjusted-means) resulted in greater stability over some of the other criteria and offered a balance of sensitivity and specificity to detect impairment; (criteria that has become known as the Jak/Bondi criteria, also referred to as neuropsychological criteria or actuarial neuropsychological for MCI).

Hence, it is interesting to explore how applying the five sets of neuropsychologically based criteria for MCI, as determined by Jak-Bondi, might influence the frequencies and characteristics of the identified SCD groups. This is particularly pertinent in memory clinics, where such patients are frequently encountered and where the differential diagnosis between SCD and MCI holds significance.

Various longitudinal studies have shown that SCD is associated with increased risk of future cognitive impairment and dementia [17]. Thus, it became crucial to establish markers for stratifying the risk of progression to dementia, namely to AD, since several studies have linked SCD to brain-based AD biomarkers [18], [19], [20]. SCD-I proposed the SCD-plus variables [13] that indicate an increased risk of developing AD. Additionally, minor neuropsychological deficits were documented as a risk factor for AD-related clinical progression in SCD patients [21]. Thus, it would be interesting to see whether using different objective cognitive test cut-offs for differentiating between SCD and MCI would disclose groups of SCD patients with differential frequencies of SCD-plus variables.

The main objective of this study is to determine the frequency of SCD diagnosis using different neuropsychological definitions of cognitive normality within a large sample of memory clinic patients. The second objective is to provide a comprehensive account of the sociodemographic and neuropsychological features, including the presence of SCD-plus variables, that characterize SCD patients diagnosed using these different definitions.

We hypothesize that using different neuropsychological definitions of cognitive normality will result in variations in the frequency of SCD diagnosis. We also anticipate that the resulting SCD diagnostic groups will have distinct profiles in terms of global cognitive performance, daily-life functioning, subjective cognitive complaints, and neuropsychiatric symptoms.

With our work, we hope to contribute to the effort of harmonizing SCD research by elucidating the limitations of the existing conceptual framework and proposing potential improvements.

Methods

Participants

This study has a cross-sectional design, recruiting participants from the Cognitive Complaints Cohort (CCC). The CCC is a clinical cohort of non-demented patients with cognitive complaints established prospectively at the Faculty of Medicine, University of Lisbon [22]. The purpose of the CCC is to evaluate the outcome of subjects with cognitive complaints based on a comprehensive neuropsychological evaluation and other biomarkers. The same team of trained neuropsychologists performs the neuropsychological assessment at each CCC visit, following a standard protocol. The inclusion criteria of the CCC are (a) the presence of cognitive complaints and (b) having a detailed neuropsychological assessment. The exclusion criteria of the CCC are (a) the presence of neurological or psychiatric disorders that may induce cognitive deficits; patients with major depression according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) [23] or serious depressive symptoms (indicated by a score of > 10 points on the Geriatric Depression Scale (GDS) short version [24]); (b) systemic illness with cerebral impact; (c) history of alcohol abuse or recurrent substance abuse or dependence and (d) presence of dementia according to DSM-IV-TR [23], or a Mini-Mental State Examination (MMSE) score below the cut-off for the Portuguese population [25], [26]. More detailed information concerning the establishment of the CCC has been previously published [27], [22], [28].

All the participants gave their informed consent to inclusion in the CCC. The study was conducted in accordance with the Declaration of Helsinki, and the local Ethics Committee of the Lisbon Academic Medical Centre (CAML) approved this specific study within the CCC. All the individuals included in the CCC between 2000 and 2022 were selected for the present study.

Diagnosis of SCD

The diagnosis of SCD was conducted by operationalizing the criteria proposed by SCD-I shown in Table 1 [13]: (a) Patients have self-experienced persistent decline if they presented to a memory clinic with a complaint of cognitive decline (SCD index criterion), and cognitive complaints were discriminated through clinical records and from the application of the Subjective Memory Complaints Scale (SMC scale) [29], [30]; (b) normal age and education-adjusted performance on extensive neuropsychological testing defined by the absence of MCI according to the five sets of MCI neuropsychologically based criteria defined by Jak and Bondi in 2009 [16] (Table 2); (c) normal global cognition defined in this study by a score ≥ 22 for those with 1–11 years of schooling and ≥ 27 for > 11 years on the MMSE [25], [26] and normal performance in activities of daily living defined in this study by a score < 3 on the first part (items 1–8) of the Blessed Dementia Rating Scale (BDRS) [31], [32], [33]; (d) absence of MCI according to the different MCI criteria examined by Jak et al. (2009) and used for criterion b) [16] or dementia defined according to DSM-IV-TR criteria [23]; (e) absence of past or present psychiatric or neurologic diseases, medical disorders, substance abuse, or use of medications that might explain the presence of subjective cognitive complaints. It should be noted that, regardless of the stage of clinical stability, patients with Neurodevelopmental Disorders, Schizophrenia Spectrum and Other Psychotic Disorders, Bipolar and Related Disorders, Depressive Disorders, and Obsessive-Compulsive and Related Disorders diagnoses according to DSM-IV-TR [23] criteria were excluded.

Table 2 Jak-Bondi MCI criteria [16]
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Significantly, the five different types of SCD considered will be determined by the Jak-Bondi rules chosen to define criterion b), as the remaining four criteria for the diagnosis of SCD remain unchanged. The SCD groups obtained by the absence of objective cognitive impairment were designated according to the respective Jak-Bondi criterion, for example, Historical SCD for the absence of Historical MCI, and so on.

The presence of SCD-plus variables (subjective decline in memory, rather than other domains of cognition, age at onset of SCD ≥ 60 years, onset of SCD within the last five years, confirmation of cognitive decline by an informant, concerns/worries associated with SCD, feeling of worse performance than others of the same age group and the presence of the APOE ε4 genotype), according to the research framework for SCD-I [13], was assessed through clinical records.

Sociodemographic data (age, sex, nationality, marital status, education, and profession), family history (psychiatric disorder and major or mild neurocognitive disorders), medical comorbidities (including the presence of arterial hypertension and diabetes mellitus), age at onset of the SCD, information regarding lifestyle, substance use, and usual medication were obtained through clinical records.

Subjective cognitive complaints

Data regarding subjective complaints were collected from clinical records, and the results of the SMC scale were applied to all patients included in CCC [29]. , [30] The SMC scale is a 10-item scale concerning difficulties in daily-life memory tasks, with total scores ranging from 0 (absence of complaints) to 21 (maximal complaints score).

Neuropsychological assessment

Global cognitive functioning data were collected from the results of the Portuguese version of the MMSE [25], [26]. The MMSE is a 30-point test, one of the most widely used brief instruments for clinical evaluation of cognitive state in adults.

Cognitive performance (age and education-adjusted) data were collected from the neuropsychological evaluation results using the Battery of Lisbon for the Assessment of Dementia (BLAD) [34], [35]. The BLAD is a comprehensive neuropsychological battery evaluating multiple cognitive domains, validated for the Portuguese population, that includes some tests from the Wechsler Memory Scale [36].

For this study, two tests from the BLAD, each with a missing data percentage below 10%, were chosen for the five cognitive domains identified by Jak and Bondi in 2009 [16]. The selected tests (domains) were logical memory delayed free recall, and five-word delayed free recall (memory); cancellation task and digit span forward (attention); verbal phonemic fluency and interpretation of proverbs (language); clock-drawing and Raven progressive matrices (visuospatial functioning); digit span backward and motor initiative (executive functioning) (Table 3).

Table 3 Neuropsychological tests
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Data regarding performance in activities of daily living were collected from the results of the first part of the BDRS that addresses daily life activities [31], [32], [30]. The BDRS is a brief behavioral scale based on the interview of a close informant, assessing functional capacity for activities of daily living and changes in personality. This scale is composed of 22 items that address daily life activities (items 1–8), habits (items 9–11), and personality changes [12,13,14,15,16,17,18,19,20,21,22].

Neuropsychiatric symptoms

The GDS [30], [37] was used to characterize depressive symptoms. The GDS is a self-report assessment explicitly used to identify depression in the elderly. A short form (15 items) of the self-report instrument was used [24], [38]. Item 10 of the GDS, “Do you feel you have more problems with memory than most?” was treated as a distinct variable of interest since it does not dichotomously assess the presence or absence of memory complaints but rather seeks to evaluate their presence or absence using as a reference measure the memory complaints that most individuals would have. This aspect holds particular relevance, as research has demonstrated that variations in SCD measurement methodologies can influence the detection of early cognitive dysfunction [39]. , [40] The third part of BDRS evaluates personality and interests and drives changes. Clinical records were also reviewed for the presence of specific neuropsychiatric symptoms.

Statistical analysis

The statistical analyses, including multiple imputation, were performed using IBM SPSS Statistics for Windows, Version 28.0.1 (SPSS Inc., an IBM Company, Chicago, IL, USA).

An area-proportional Venn Diagram was generated to visually represent the differences and the similarities between the five SCD diagnostic groups using the DeepVenn Web application [41]. GraphPad Prism 10.2.0 (392) for Windows (GraphPad Software, Inc., San Diego, Calif., USA) was also used for graphical displays.

The sociodemographic, clinical, and neuropsychological data of each SCD diagnostic group were described using descriptive statistics. The neuropsychological assessments were standardized according to the age and education norms for the Portuguese population [42], and z-scores were calculated. The frequencies of SCD were computed considering the number of patients with SCD, according to the five different objective cognitive thresholds and considering three discrete intervals (0: absence of any SCD-plus variable; 1–3: presence of one to three SCD-plus variables, 4–7: presence of four or more SCD-plus variables).

To know whether the 5 SCD criteria might describe distinct patient populations, a bootstrap methodology [43] was employed to estimate the mean and 95% confidence intervals (CI) for specific parameters of interest, namely SMC scale (subjective cognitive complaints), MMSE (global cognition), BDRS first part (daily living functioning), and GDS (psychiatric symptoms), within each of the five SCD diagnostic groups. The means were considered statistically significantly different when the 95% CIs did not overlap (P2.5 and P97.5 were used as the limits of the non-parametric bootstrap CI for the mean).

Missing data were treated according to the principles of the TRIPOD statement [44]. Considering that the proportion of missing data among the ten employed neuropsychological tests was less than 10% and that the predominant absence of values in these variables is assumed to stem from random causes, the multiple imputation methodology [45], [46] was selected to address these variables. Recognizing the potential substantive contribution of additional variables to the imputed values, a multiple imputation model was formulated encompassing fourteen variables (ten neuropsychological tests, a metric for global cognitive performance (MMSE), a metric for subjective cognitive complaints (SMC scale), a metric for daily life functioning (first part of the BDRS), and a metric for neuropsychiatric symptoms (third part of the BDRS)). The automatic imputation method was selected in SPSS. After analyzing the data and considering that all fourteen variables were of a scale nature, SPSS employed the Monte Carlo method [47] for imputation, utilizing a linear regression analysis. Five sets of imputations were generated. The average of the five imputations for neuropsychological test variables was calculated to obtain the final data set.

Results

1417 patients were enrolled in the CCC between January 1, 2000, and December 31, 2022 (Fig. 1). Upon review of these patients’ clinical records and application of the SCD-I criteria (a), c), d), and e)), 149 patients were excluded due to insufficient clinical data, presence of dementia criteria, significant psychiatric disorders, and relevant non-psychiatric disorders, notably significant cerebrovascular disease. Consequently, 1268 subjects were included in this study.

Fig. 1
figure 1

Patient enrolment, from CCC to SCD-I criteria

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Frequencies of SCD diagnostic groups

Using different objective cognitive boundaries to define SCD (SCD-I criterion b), there was a considerable variation among subjects diagnosed with SCD, ranging from 208 (16.4%) (Liberal SCD) to 1031 (81.3%) (Conservative SCD). The SCD groups obtained by varying the definition of MCI according to Jak-Bondi criteria are also visually represented in Fig. 2. Only 207 subjects (16.3%) were diagnosed with SCD according to all 5 SCD criteria, roughly corresponding to the Liberal SCD group (n = 208). The only participant excluded from the Liberal SCD group would not be diagnosed with SCD solely based on the Comprehensive criteria. However, it would still be considered SCD according to the other four criteria. Only 197 subjects (15.5%) were considered SCD according to 4 SCD criteria (Conservative, Comprehensive, Historical, and Typical), and 284 (22.4%) were considered SCD according to 3 criteria (Comprehensive, Conservative, and Historical).

Fig. 2
figure 2

Venn diagram of SCD diagnostic groups

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Demographic variables and clinical characteristics of SCD diagnostic groups

The sociodemographic data and clinical characteristics of SCD patients diagnosed according to the five criteria are presented in Table 4. It is important to note that the different diagnostic groups of SCD share common patients. Therefore, a direct comparison between these groups was not conducted. Instead, we report descriptively the most relevant characteristics and their variations across the different diagnostic groups of SCD.

Table 4 Demographic and clinical characteristics of SCD patients diagnosed according to the five different criteria
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Across all SCD diagnostic groups, nearly two-thirds of the subjects were women. Age and educational levels remained consistent regardless of the SCD diagnostic group, with mean ages ranging from 66.6 years (Typical SCD) to 68.4 years (Conservative SCD) and average educational levels ranging from 10.0 years (Conservative SCD) to 11.3 years (Liberal SCD).

The SCD-plus variables were present in virtually all individuals. The presence of 4 or more of these variables varied between 67.8% (Historical SCD) and 71.6% (Liberal SCD). Irrespective of the SCD diagnostic group, the most prevalent SCD-plus variable was the onset of cognitive decline in the last five years, followed successively by cognitive decline in memory, concerns associated with SCD, onset age greater than or equal to 60 years, and confirmation of cognitive decline by an informant.

The Liberal SCD group exhibited the highest average score on the MMSE (28.2), while the Conservative SCD group had the lowest average MMSE score (27.2).

Regardless of how memory complaints were assessed, there were numerous complaints across all SCD diagnostic groups.

Regarding performance in activities of daily living, the Liberal SCD group showed the best performance in the first part of the BDRS (0.3). In contrast, the Conservative SCD group exhibited the worst performance (0.8).

Lastly, concerning psychiatric symptoms, the Liberal SCD group had the lowest frequency of psychiatric symptoms, as measured by both the third part of the BDRS and the GDS. This group also had the lowest percentage of documented depression in the clinical interview.

Performance of SCD diagnostic groups on the neuropsychological tests

The neuropsychological characteristics of SCD patients diagnosed according to the five criteria are shown in Table 5. The neuropsychological evaluation results of SCD patients are presented as the means of z scores for each test according to age and education norms for the Portuguese population (Table 5). Considering the overall performance in the neuropsychological assessment, the Historical SCD group exhibited the poorest performance, with average negative z-scores in all tests across the memory and attention domains and in the motor initiative (executive functions). In contrast, the Liberal SCD group demonstrated the best overall performance in the neuropsychological assessment, with no test having a negative average z-score. Interestingly, irrespective of the SCD diagnostic group, subjects displayed their poorest overall performance in memory tests. In contrast, their best overall performance, with no negative average z-scores, was consistently observed in language tests.

Table 5 Neuropsychological performance of SCD patients diagnosed according to the five different criteria
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Clinical populations represented by SCD diagnostic groups

We performed a bootstrap analysis to test the hypothesis that the SCD patients diagnosed according to the five criteria would represent distinct clinical populations (Fig. 3). The colored spots represent variables with means whose 95% CI does not overlap with other variables.

Fig. 3
figure 3

Bootstrap analysis of SMC scale, MMSE, BDRS first part, and GDS. The colored spots represent variables with means whose 95% CI does not overlap with other variables. Abbreviations: BDRS, Blessed Dementia Rating Scale; GDS, Geriatric Depression Scale; MMSE, Mini-Mental State Examination; SMC, Subjective Memory Complaints

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Considering the confidence intervals obtained, applying the different criteria selected patients representative of distinct populations in terms of global cognitive performance (assessed by the MMSE, Fig. 3A) and activities of daily living (as measured by the first part of the BDRS, Fig. 3B). Notably, the Conservative SCD was associated with a population of patients exhibiting poorer global cognitive functioning (MMSE: mean 27.15, 95% CI 27.00-27.31) since its 95% CI did not overlap with any other. The Liberal SCD group appears to correspond to a population with better global cognitive functioning than the Conservative SCD and Historical SCD groups. However, its 95% CI overlaps with the Comprehensive SCD and Typical SCD groups, while these overlap with the Historical SCD group.

Regarding activities of daily living, Liberal SCD (BDRS first part: mean 0.30, 95% CI 0.23–0.38) stood out as representative of a population exhibiting better performance than Typical SCD (BDRS first part: mean of 0.46 and 95% CI 0.40–0.53), and both better performance than Comprehensive, Conservative and Historical SCD that do not differ from each other.

On the other hand, the application of the five different diagnostic criteria resulted in SCD groups of patients representing populations not distinguishable regarding subjective cognitive complaints (as assessed by the SMC scale) and neuropsychiatric symptoms (measured using the GDS) (Fig. 3, C, and D).

Discussion

The most important finding was that applying criteria with different neuropsychological definitions of cognitive normality in a large sample of memory clinic patients resulted in substantial variations in the frequency of SCD diagnosis, varying between 16.4% (Liberal SCD) and 81.3% (Conservative SCD). Furthermore, patients diagnosed with different criteria showed distinct clinical characteristics; Conservative SCD represented a population of patients with poorer global cognitive functioning, while Liberal SCD showed better performance in activities of daily living than Typical SCD, and both better performance than Comprehensive, Conservative, and Historical SCD.

We hypothesized that employing various neuropsychological definitions of cognitive normality would lead to fluctuations in the frequency of SCD diagnosis. The previously mentioned study of Jak et al. (2009) reported that 10–74% of participants would receive the diagnosis of MCI depending on the diagnostic strategy. Indeed we found that, when different criteria are applied to diagnose SCD, the frequency of diagnosis varies considerably. It spanned from 16.4% (Liberal SCD), a rate more aligned with the reported prevalence of SCD in international cohort studies of aging [48], which generally falls around one-quarter of patients, to 81.3% (Conservative SCD), a proportion even surpassing that reported in certain studies examining SCD in older populations [49]. For instance, a recent systematic review in older adults indicated a prevalence of SCD among patients over 80 years old of 60.3% [49]. The SCD prevalence obtained using Conservative criteria is much more in line with studies that use community samples and various self-report measures, where nearly all elderly people may experience SCD [8], [50].

We also anticipated that the obtained SCD diagnostic groups might have distinct profiles in terms of global cognitive performance. This hypothesis was confirmed by the bootstrap approach, with Conservative SCD being associated with a population of patients exhibiting poorer global cognitive functioning and the Liberal SCD group appearing to correspond to a population with better global cognitive functioning than the Conservative SCD and Historical SCD groups. In line with these results, the bootstrap analysis also revealed that, in terms of daily-life functioning, SCD diagnostic groups exhibited distinct profiles, with the Typical SCD standing out as representative of a population exhibiting a worse performance when compared with the Liberal SCD criteria but a better performance than Comprehensive, Conservative, and Historical SCD that do not differ from each other.

The notable variability in the frequency of diagnosing SCD, depending on the specific criteria used for cognitive impairment assessment, presents significant challenges in the already intricate process of counseling these patients after SCD diagnosis and in determining appropriate follow-up protocols [15]. It is thus of clinical importance to specify the criteria employed for SCD diagnosis, as this appears to dictate the ability to identify distinct populations. Consequently, a patient diagnosed with SCD using Conservative MCI criteria is more likely to exhibit relatively worse cognition and function compared to SCD classified using more liberal criteria for cognitive impairment.

Conversely, individuals classified as SCD according to Liberal MCI criteria are broadly categorized as such, regardless of the criteria used, and seem to represent a cohort exhibiting better cognitive preservation and daily functioning. It appears clear that various diagnostic criteria for SCD may hold different relevance depending on the clinical setting. However, contrary to what we had anticipated, these groups do not seem to be particularly distinguished by the amount of subjective cognitive complaints or by the extent of neuropsychiatric symptoms, especially depressive symptoms [51].

The higher frequency of individuals with four or more SCD-plus variables in our sample, varying between 67.8% and 71.6% across the different SCD diagnostic groups, is an interesting finding, particularly when compared to analogous studies [52], where the prevalence of SCD patients with three or more SCD-plus variables was estimated as about 45%. Given that SCD-plus variables are associated with a higher risk of cognitive decline, one might question whether the use of different neuropsychological criteria for defining cognitive impairment would also allow for the selection of groups of patients with SCD at a higher risk for future cognitive deterioration. However, the marginal fluctuation in the prevalence of SCD-plus variables across distinct diagnostic SCD groups suggests that these criteria may not detect different probabilities of neurodegenerative disease. Conservative SCD individuals showed inferior performance in global cognitive functioning and activities of daily living, suggesting that Conservative MCI criteria results in underdiagnosing MCI, and those MCI individuals then end up in the SCD group, making the overall global cognition and functioning lower. Indeed, we advance the possibility that the diagnosis of SCD using the MCI Conservative criteria might represent a novel SCD-plus variable.

Using sensitive markers such as process scores to detect subtle cognitive decline before the onset of MCI, like the concept of objectively-defined subtle cognitive decline defined by Thomas and colleagues [53], may help in detecting individuals with SCD who are at risk of progressing. Further, combining various neuropsychological criteria that define cognitive impairment with SCD-plus variables, alongside other sociodemographic and clinical data, namely the performance in functional activities, seems a promising strategy [54], but presents a complex challenge. Approaches such as Artificial Intelligence, which have shown promise in investigating cognitive decline [55], particularly in early detection [56], may offer a beneficial strategy to tackle this challenge.

Limitations to the current study should be noted. The cross-sectional design does not allow for drawing definitive conclusions about the comparative ability of these criteria to detect patients at an early stage of neurodegenerative diseases. However, we sought to counterbalance this limitation by quantifying the SCD-plus characteristics within each diagnostic group. Given that this is a sample of patients from a single-memory clinic, the findings may not be generalizable to other clinical settings. Despite the mentioned limitations, this study has relevant strengths. The large sample size allowed capture of the variety and heterogeneity of SCD. The use of a well-established and long-standing clinical cohort allowed for the extensive characterization of the participants. The validated assessment tools ensured the reliability and validity of the results. The systematic comparison of all the 5 neuropsychological criteria from Jak and colleagues was performed. And, finally, it was possible to detail how different criteria select patients representative of distinct populations in terms of global cognition and activities of daily living.

We consider that the present findings need to be corroborated through a longitudinal study that might prospectively evaluate, over an adequate time interval, patients diagnosed according to different SCD criteria regarding the percentage of conversion to MCI and dementia, identifying the etiology of the neurocognitive disturbances and better-characterizing personality traits and the evolution of neuropsychiatric symptoms within each group.

Conclusions

In conclusion, applying diagnostic criteria with different neuropsychological definitions of cognitive normality significantly changes the frequency and characteristics of SCD in a sample of patients from a memory clinic. Therefore, it is essential to specify the criterion when diagnosing a SCD patient and to understand the risks and benefits of using different criteria to define cognitive impairment.

Data availability

The datasets used during the current study are available from the corresponding author on reasonable request.

Abbreviations

BDRS:

Blessed Dementia Rating Scale

BLAD:

Battery of Lisbon for the Assessment of Dementia

CAML:

Lisbon Academic Medical Centre

CCC:

Cognitive Complaints Cohort

CI:

Confidence Intervals

GDS:

Geriatric Depression Scale

MCI:

Mild Cognitive Impairment

MMSE:

Mini-Mental State Examination

SCD:

Subjective Cognitive Decline

SCD-I:

Subjective Cognitive Decline Initiative

SMC scale:

Subjective Memory Complaints Scale

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Acknowledgements

The authors thank Memoclínica for the facilities provided.

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Authors and Affiliations

  1. Psychiatry and Mental Health Department, Unidade Local de Saúde de Santa Maria, Av. Prof. Egas Moniz MB, Lisbon, Lisboa, 1649-028, Portugal

    Pedro Câmara Pestana & Frederico Simões do Couto

  2. University Clinic of Psychiatry and Medical Psychology, Lisbon Medical School, University of Lisbon, Lisbon, Portugal

    Pedro Câmara Pestana

  3. Institute of Environmental Health (ISAMB), Lisbon Medical School, University of Lisbon, Lisbon, Portugal

    Pedro Câmara Pestana

  4. Católica Medical School, Universidade Católica Portuguesa, Lisboa, Portugal

    Pedro Câmara Pestana & Frederico Simões do Couto

  5. Faculty of Medicine, University of Lisbon, Lisbon, Portugal

    Sandra Cardoso, Manuela Guerreiro & Alexandre de Mendonça

  6. ISPA - Instituto Universitário de Ciências Psicológicas, Sociais e da Vida, Lisbon, Portugal

    João Maroco

  7. Department of Psychiatry, University of Cologne, Cologne, Germany

    Frank Jessen

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Contributions

PCP: study conception and design; data collection; analysis and interpretation of results; draft manuscript preparation. SC: data collection; analysis and interpretation of results. MG: study conception and design; manuscript critical revision. JM: statistical review; manuscript critical revision. FJ: study conception and design; manuscript critical revision. FSC: study conception and design; manuscript critical revision. AM: study conception and design; manuscript critical revision. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Pedro Câmara Pestana.

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All the participants gave their informed consent to inclusion in the CCC. The study was conducted in accordance with the Declaration of Helsinki, and the local Ethics Committee of the Lisbon Academic Medical Centre approved this specific study within the CCC.

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Pestana, P.C., Cardoso, S., Guerreiro, M. et al. Frequency, sociodemographic, and neuropsychological features of patients with subjective cognitive decline diagnosed using different neuropsychological criteria. Alz Res Therapy 16, 261 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13195-024-01634-1

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Keywords

Alzheimer's Research & Therapy

ISSN: 1758-9193