Beauty and Paintings: Aesthetic Experience in Patients with Behavioral Variant Frontotemporal Dementia When Viewing Abstract and Concrete Paintings.

We assessed the aesthetic experience of patients with behavioral variant frontotemporal dementia (bvFTD) to understand their ability to experience feelings of the sublime and to be moved when viewing paintings. We exposed patients with bvFTD and control participants to concrete and abstract paintings and asked them how moved they were by these paintings and whether the latter were beautiful or ugly. Patients with bvFTD declared being less moved than control participants by both abstract and concrete paintings. No significant differences were observed between abstract and concrete paintings in both patients with bvFTD and control participants. Patients with bvFTD provided fewer "beautiful" and more "ugly" responses than controls for both abstract and concrete paintings. No significant differences in terms of "beautiful" and "ugly" responses were observed between abstract and concrete paintings in both patients with bvFTD and control participants. These findings suggest disturbances in the basic affective experience of patients with bvFTD when they are exposed to paintings, as well as a bias in their ability to judge the aesthetic quality of paintings.

ChatGPT as a Diagnostic Aid in Alzheimer's Disease: An Exploratory Study.

Background: The potential of ChatGPT in medical diagnosis has been explored in various medical conditions. Objective: We assessed whether ChatGPT can contribute to the diagnosis of Alzheimer's disease (AD). Methods: We provided ChatGPT with four generated cases (mild, moderate, or advanced stage AD dementia, or mild cognitive impairment), including descriptions of their complaints, physical examinations, as well as biomarker, neuroimaging, and neuropsychological data. Results: ChatGPT accurately diagnosed the test cases similarly to two blinded specialists. Conclusions: While the use of generated cases can be a limitation to our study, our findings demonstrate that ChatGPT can be a useful tool for symptom assessment and the diagnosis of AD. However, while the use of ChatGPT in AD diagnosis is promising, it should be seen as an adjunct to clinical judgment rather than a replacement.

Assessment of Mendelian and risk-factor genes in Alzheimer disease: A prospective nationwide clinical utility study and recommendations for genetic screening.

PURPOSE: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD). METHODS: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) ≤65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92). RESULTS: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees. CONCLUSION: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure.

The guaranteed euros: Probabilistic discounting in behavioural-variant frontotemporal dementia.

Financial decision-making requires trading off between guaranteed and probabilistic outcomes and between immediate and delayed ones. While research has demonstrated that patients with behavioural-variant frontotemporal dementia (bvFTD) prefer immediate rewards at the expense of future ones (i.e. temporal discounting), little is known about how patients choose between smaller, guaranteed and larger, but probabilistic, outcomes (i.e. probabilistic discounting). We thus investigated probabilistic discounting by inviting 18 patients with bvFTD and 20 control participants to choose between fixed smaller monetary amounts and a fixed larger monetary amount with a variated probability of occurrence (e.g. 'Would you rather have 40€ for sure or a 20% chance of winning 100€?'). Results demonstrated lower scores, indicating higher risk tolerance, on the probabilistic discounting task in patients with bvFTD (while impulsively choosing more immediate rewards on the temporal discounting task) compared to control participants. Probabilistic discounting was significantly correlated with a decline in general cognitive performance in patients with bvFTD. When dealing between smaller, guaranteed, and larger, but probabilistic, rewards, patients with bvFTD tend to prefer guaranteed rewards and discount the uncertain ones.

ChatGPT's dance with neuropsychological data: A case study in Alzheimer's disease.

Artificial intelligence continues to revolutionize the medical and scientific field, especially with the release of ChatGPT. We assessed whether it provides an accurate interpretation of neuropsychological screening. We provided ChatGPT with the neuropsychological data of a patient with mild Alzheimer's Disease and invited it and two neuropsychologists to interpret the data. While ChatGPT provided an accurate interpretation of scores on each of the neuropsychological tests, it did not use standardized scores and did not specify the cognitive domain that may be most impaired. In contrast, the neuropsychologists used standardized scores to determine that the patient was mainly suffering from memory decline. While ChatGPT may succeed in the general interpretation of neuropsychological testing, at least in patients with Alzheimer's Disease, it still cannot create a pattern of scores across different tests to better specify the nature of cognitive impairment.

The neutral past: emotional (dys)regulation of autobiographical memory in behavioural variant frontotemporal dementia.

BACKGROUND: While affective disturbances are a key symptomatic indicator of behavioural variant frontotemporal dementia (bvFTD), little is known about how patients process the emotional load of their autobiographical (i.e. personal) memories. METHODS: We assessed the interplay of emotional regulation and autobiographical memory by inviting 18 bvFTD and 20 control participants to remember past personal events. For each memory, participants rated its emotional valence "then" (i.e. when the event has occurred) vs "now" (i.e. when retrieving the event). RESULTS: Patients with bvFTD described their memories as neutral at both times (p = .85), while control participants rated their memories as more positive during "then" than during "now" (p = .013). Autobiographical retrieval triggered fewer emotional words (p < .001) and less specificity (p < .001) in bvFTD patients compared to control participants. CONCLUSIONS: The lack of significant differences between the emotional characteristics during "then" than "now" in patients with bvFTD (and the flattening of both) may mirror their hampered ability for emotional generation, which may be associated with difficulties in reframing their past experiences to modify and adapt their meaning. The hampered emotional regulation in bvFTD may also be associated with an avoidance strategy and a passive attitude toward the past.

Different Trajectories of Apathy and Depression Among Subjective Cognitive Impairment Individuals with or without Conversion to Dementia: Results from the Memento Cohort in France.

BACKGROUND: Apathy and depression are two early behavioral symptoms in Alzheimer's disease (AD) and related disorders that often occur prior to the onset of cognitive decline and memory disturbances. Both have been associated with an increased risk of conversion to dementia, with a distinct neuropathology. OBJECTIVE: The assessment of the trajectories of apathy and depression and their independent impact on dementia conversion. METHODS: Apathy and Depression were measured using the Neuropsychiatric Inventory for caregiver (NPI) and clinician (NPI-C), among the nondemented individuals reporting subjective cognitive decline (SCD) at baseline. They were followed up over a 60-month period. Some converted to dementia, according to the methodology carried out by the French Memento Cohort. RESULTS: Among individuals with SCD (n = 2,323), the levels of apathy and depression were low and did not evolve significantly over the 60-month period, despite a trend in apathy increasing as of month 24. Regarding SCD individuals who converted to dementia within the 60-month period (n = 27), the prevalence of depression remained globally steady, while the levels of apathy increased over time. CONCLUSION: Apathy and depression have different trajectories among individuals with SCD and apathy alone is more likely-compared to depression-to be associated with conversion to dementia.

The Pupil Knows: Pupil Dilation Indexes and Their Inhibitory Ability in Normal Aging.

Pupil dilation is considered an index of cognitive effort, as the pupil typically dilates as the cognitive load increases. In this paper, we evaluated whether older adults demonstrate increased pupil size when performing tasks requiring cognitive inhibition. We invited 44 older and 44 younger adults to perform the Stroop task while their pupil dilation was recorded with eye-tracking glasses. The dependent variables were the number of accurate responses on the Stroop task as well as pupil size in the three conditions of the task (i.e., color naming, word reading, and the interference condition). The results demonstrated less accurate responses in the interference condition than in the color-naming or word-reading conditions, in both older and younger adults. Critically, larger pupil dilation was observed in the interference condition than in the color-naming and word-reading conditions, in both older and younger adults. This study demonstrates that pupil dilation responds to cognitive effort in normal aging, at least in the interference condition of the Stroop task.

Plasma lysosphingolipids in GRN-related diseases: Monitoring lysosomal dysfunction to track disease progression.

GRN mutations are among the main genetic causes of frontotemporal dementia (FTD). Considering the progranulin involvement in lysosomal homeostasis, we aimed to evaluate if plasma lysosphingolipids (lysoSPL) are increased in GRN mutation carriers, and whether they might represent relevant fluid-based biomarkers in GRN-related diseases. We analyzed four lysoSPL levels in plasmas of 131 GRN carriers and 142 non-carriers, including healthy controls and patients with frontotemporal dementias (FTD) carrying a C9orf72 expansion or without any mutation. GRN carriers consisted of 102 heterozygous FTD patients (FTD-GRN), three homozygous patients with neuronal ceroid lipofuscinosis-11 (CLN-11) and 26 presymptomatic carriers (PS-GRN), the latter with longitudinal assessments. Glucosylsphingosin d18:1 (LGL1), lysosphingomyelins d18:1 and isoform 509 (LSM18:1, LSM509) and lysoglobotriaosylceramide (LGB3) were measured by electrospray ionization-tandem mass spectrometry coupled to ultraperformance liquid chromatography. Levels of LGL1, LSM18:1 and LSM509 were increased in GRN carriers compared to non-carriers (p < 0.0001). No lysoSPL increases were detected in FTD patients without GRN mutations. LGL1 and LSM18:1 progressively increased with age at sampling, and LGL1 with disease duration, in FTD-GRN. Among PS-GRN carriers, LSM18:1 and LGL1 significantly increased over 3.4-year follow-up. LGL1 levels were associated with increasing neurofilaments in presymptomatic carriers. This study evidences an age-dependent increase of ß-glucocerebrosidase and acid sphingomyelinase substrates in GRN patients, with progressive changes as early as the presymptomatic phase. Among FTD patients, plasma lysoSPL appear to be uniquely elevated in GRN carriers, and thus might serve as suitable non-invasive disease-tracking biomarkers of progression, specific to the pathophysiological process. Finally, this study might add lysoSPL to the portfolio of fluid-based biomarkers, and pave the way to disease-modifying approaches based on lysosomal function rescue in GRN diseases.

"Who am I?": Weakened sense of the self in patients with behavioral variant frontotemporal dementia.

While research has shown a distrusted sense of the self in patients with behavioral variant frontotemporal dementia (bvFTD), little is known about how patients describe their self-image. We used the "Who am I?" task to invite patients with bvFTD and control participants to produce statements beginning with "I am…." We distinguished between statements related to physical, social, and psychological self. Analyses showed fewer statements related to physical, social, and psychological self in the patients with bvFTD than in control participants. Another result was the proportionally similar production of statements describing physical, social, and psychological self in both patients with bvFTD and control participants. Finally, the total production of "Who am I?" statements was positively correlated with verbal fluency in both patients with bvTFD and control participants. Our findings demonstrate a diminished ability of patients with bvFTD to process self-images. Our study also paves the way toward the use of the "Who am I" task as a simple and ecologically valid tool allowing for the quantitative and qualitative assessment of the sense of self in patients with bvFTD.

How Do Women and Men Look at the Past? Large Scanpath in Women during Autobiographical Retrieval-A Preliminary Study.

While research has consistently demonstrated how autobiographical memory triggers visual exploration, prior studies did not investigate gender differences in this domain. We thus compared eye movement between women and men while performing an autobiographical retrieval task. We invited 35 women and 35 men to retrieve autobiographical memories while their gaze was monitored by an eye tracker. We further investigated gender differences in eye movement and autobiographical specificity, that is, the ability to retrieve detailed memories. The analysis demonstrated shorter fixations, larger duration and amplitude of saccades, and higher autobiographical specificity in women than in men. The significant gender differences in eye movement disappeared after controlling for autobiographical specificity. When retrieving autobiographical memory, female participants generated a large scan with short fixation and high saccade amplitude, while male participants increased their fixation duration and showed poorer gaze scan. The large saccades in women during autobiographical retrieval may constitute an exploratory gaze behavior enabling better autobiographical memory functioning, which is reflected by the larger number of autobiographical details retrieved compared to men.

Brain Metabolic Profile in Presymptomatic GRN Carriers Throughout a 5-Year Follow-up.

BACKGROUND AND OBJECTIVES: GRN variants are a frequent cause of familial frontotemporal dementia (FTD). Monitoring disease progression in asymptomatic carriers of genetic variants is a major challenge in delivering preventative therapies before clinical onset. This study aimed to assess the usefulness of fluorodeoxyglucose (FDG)-PET in identifying metabolic changes in presymptomatic GRN carriers (PS-GRN+) and to trace their longitudinal progression. METHODS: Participants were longitudinally evaluated over 5 years in a prospective cohort study focused on GRN disease (Predict-PGRN). They underwent cognitive/behavioral assessment, plasma neurofilament measurement, brain MRI, and FDG-PET. Voxel-wise comparisons of structural and metabolic imaging data between 2 groups were performed for each time point. Longitudinal PET changes were evaluated with voxel-wise comparisons and the metabolic percent annual changes method. The association of regional brain metabolism with plasma neurofilament and cognitive changes was analyzed. RESULTS: Among the 80 individuals enrolled in the study, 58 (27 PS-GRN+ and 31 noncarriers) were included in the analyses. Cross-sectional comparisons between PS-GRN+ and controls found a significant hypometabolism in the left superior temporal sulcus (STS) region (encompassing the middle and superior temporal gyri), approximately 15 years before the expected disease onset, without significant cortical atrophy. The longitudinal metabolic decline over the following 5 years peaked around the right STS in carriers (p < 0.001), without significantly greater volume loss compared with that in controls. Their estimated annualized metabolic decrease (-1.37%) was higher than that in controls (-0.21%, p = 0.004). Lower glucose uptake was associated with higher neurofilament increase (p = 0.003) and lower frontal cognitive scores (p = 0.014) in PS-GRN+. DISCUSSION: This study detected brain metabolic changes in the STS region, preceding structural and cognitive alterations, thus contributing to the characterization of the pathochronology of preclinical GRN disease. Owing to the STS involvement in the perception of facially communicated cues, it is likely that its dysfunction contributes to social cognition deficits characterizing FTD. Overall, our study highlights brain metabolic changes as an early disease-tracking biomarker and proposes annualized percent decrease as a metric to monitor therapeutic response in forthcoming trials.

Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort.

BACKGROUND AND OBJECTIVE: Blood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints. METHODS: The MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI, and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aß42/40 ratio, total tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period. RESULTS: Overall, 2,277 individuals had at least 1 baseline blood biomarker available (n = 357 for CSF subsample, n = 649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total tau were mildly correlated with their equivalence in the CSF (r = 0.33 to 0.46, p < 0.0001) and were associated with amyloid-PET status (p < 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 [95% CI = 0.69; 0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aß42/40 was less efficient than CSF Aß42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 [95% CI = 0.69; 0.77]); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 [95% CI = 0.69; 0.97]) than in patients with CDR = 0.5 (c-index = 0.70 [95% CI = 0.66; 0.74]). A "clinical" reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 [95% CI = 0.86-0.91] and performance increased to 0.90 [95% CI = 0.88; 0.92] when adding blood p181-tau + Aß42/40. A "research" reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 [95% CI = 0.89-0.93] increasing to 0.92 [95% CI = 0.90; 0.93] when adding blood p181-tau + Aß42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances. DISCUSSION: In a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.

Does a rabbit have feathers or fur? Development of a 42-item semantic memory test (SMT-42).

OBJECTIVE: We present the preliminary study of the 42-item Semantic Memory Test (SMT-42), a test developed to distinguish semantic variant primary progressive aphasia (svPPA) from the other variants: logopenic (lPPA) and nonfluent/agrammatic (naPPA). The test requires the patient to retrieve the conceptual features of items belonging to different lexical categories. METHODS: In the first study, we administered the French version of the SMT-42 to a population of healthy subjects and to patients with svPPA matched to a subgroup of the healthy subjects. In the second study, we administered the SMT-42 to four groups of patients (with svPPA, lPPA, naPPA and Alzheimer's disease [AD], respectively) to study its capacity to differentiate patients suffering from svPPA from the other patients. RESULTS: In the first study, 109 healthy subjects were included, 15 of whom were paired with 15 subjects presenting with svPPA. In the second study, designed to compare groups presenting a primary progressive aphasia variant and AD, 12 subjects with svPPA, 6 with naPPA and 9 with lPPA were included, along with 21 subjects with AD. The subjects presenting a semantic deficit were clearly distinguished from the others by their results on the SMT-42 (svPPA: mean = 30.0 (5.9); lPPA: mean = 37.8 (3.3), d = 1.5, p = 0.002; naPPA: mean = 39.8 (1.9), d = 1.89, p = 0.001; AD: mean = 38.5 (2.4), d = 1.63, p < 0.001); (svPPA: median = 31; lPPA: median = 38, U = 9, p = 0.002; naPPA: median = 40.5, U = 1.5, p = 0.001; AD: median = 39, U = 13.5, p < 0.001). CONCLUSION: The SMT-42 is simple, rapidly administered (3 minutes on average), easily scored and has good sensitivity, and it appears to be an effective tool for semantic screening in routine clinical practice.

Does Sex Matter? High Semantic Autobiographical Retrieval in Women and Men With Alzheimer's Disease.

The decline of autobiographical memory in Alzheimer's disease (AD) is mainly characterized by overgenerality. While there is a large body of research on autobiographical overgenerality in AD, this research has mainly assessed retrieval with a dichotomy between specific vs. general retrieval. To go beyond this dichotomy, we assessed several degrees of autobiographical specificity in patients with AD, namely, we assessed specific vs. categoric vs. extended vs. semantic retrieval. We also assessed sex differences regarding these degrees of autobiographical specificity. We invited patients with mild AD and control participants to complete sentences (e. g., "When I think back to/of…") with autobiographical memories. Memories were categorized into specific, categoric, extended, or semantic memories. Results demonstrated more semantic than specific, categoric or extended memories in men and women with AD. In control participants, analysis demonstrated more specific than categoric, extended, and semantic memories in men and women. Also, no significant differences were observed between women and men with AD, or between control women and men, regarding specific, categoric, extended, and semantic memoires. This study offers not only a nuanced analysis of autobiographical specificity in patients with mild AD, but also an original analysis regarding this specificity by sex.

"Look at the future": Maintained fixation impoverishes future thinking.

We evaluated the relationship between eye movements and future thinking. More specifically, we evaluated whether maintained fixation could influence cognitive characteristics of future thinking. We invited participants to imagine future events in two conditions: while freely exploring a white wall and while fixating a cross on the wall. Results demonstrated fewer and longer fixations, as well as fewer and shorter saccades during maintained fixation condition than in the free gaze condition. Shorter total amplitude of saccades was also observed during the maintained fixation condition than during the free-gaze condition. Regarding the cognitive characteristics of future thinking, fewer spatiotemporal details and less visual imagery, slower retrieval time, and shorter descriptions were observed for future thinking during maintained fixation than during free-gaze condition. These results demonstrate that maintaining fixation results in an effortful construction of future scenarios. We suggest that maintained fixation limits the cognitive resources that are required for future thinking.

Empathy of individuals with Alzheimer's disease (AD) toward other AD patients.

BACKGROUND: The objective of this study was twofold. We assessed whether individuals with Alzheimer's disease (AD) demonstrate higher empathy toward people with the same disorder. We also assessed whether empathy may enhance the recognition of these peoples' faces. METHOD: Twenty-seven mild AD participants and 30 healthy older adults were invited to retain faces depicting either people diagnosed with AD or healthy people. Participants were also invited to rate their empathy toward all faces. RESULTS: Although AD participants reported higher empathy for "AD-labeled" than for "healthy" faces, recognition was similar for both categories of faces. Healthy older adults also reported higher empathy for "AD-labeled" than for "healthy" faces. However, they demonstrated higher recognition for "healthy" than for "AD-labeled" faces. CONCLUSIONS: Although our paper shows no effect of empathy on face recognition in AD, it provides a clinically relevant finding: individuals with mild AD can demonstrate significant empathy toward people with the same medical condition.

Pupillometry as an index for cognitive processing in behavioral variant FrontoTemporal Dementia: a series of case studies.

We investigated whether pupil size can variate with the intensity of cognitive processing in patients with behavioral-variant-Frontotemporal-Dementia (bvFTD). We invited five bvFTD participants and 21 controls to perform forward spans and backward spans, and, in a control condition, to count aloud. We recorded pupil activity using eye-tracking-glasses during the spans and control condition. Analysis demonstrated larger pupil sizes during backward spans than during forward spans, and larger pupil sizes during forward spans than during counting in both bvFTD and control participants. These findings demonstrate how increased cognitive load triggers increased pupil size and how this connection is maintained in bvFTD.

On Covid-19 and mental health: An observational study on depression, anxiety, and loneliness during the second lockdown in patients with Alzheimer disease.

ABSTRACT: While visiting and socialization restrictions during lockdowns were instituted to cope with the Covid-19 spread and to prolong the life of residents of retirement homes, these measures could have been expected to decrease the quality of life of their residents.We assessed longitudinal effects of the two successive lockdowns, as implemented in France, on mental health (i.e., depression, anxiety, and loneliness) in 62 retirement home residents with Alzheimer disease (AD).Analysis demonstrated higher levels of depression, anxiety, and loneliness during the second lockdown than during the first lockdown.The increased levels of depression, anxiety, and loneliness during the second lockdown can be attributed to the longer duration of the restrictive measures, especially the restriction of visits, that were implemented in retirement homes. In addition, the increased workload of geriatric healthcare workers leading to higher levels of burnout and decreased quality of care may help explain the increased loneliness, depression, and anxiety of retirement home residents with AD, which were observed during the second Covid-19 era lockdown.

"Who will I be?": The future of the self as described by Alzheimer's disease (AD) patients.

We assessed how Alzheimer's disease (AD) patients would imagine their self in the future. AD patients and healthy controls were asked to generate statements beginning with "I-will-be" to describe how they saw themselves or how they wished to be in the future. These statements were analyzed in terms of four self-dimensions, i.e., physical self, social self, psychological self and self-cessation. The latter was investigated to assess how AD patients processed the idea of their own mortality. Findings demonstrated fewer total "I-will-be" statements in AD participants than in controls, suggesting that the construction of future self-concepts becomes weaker in the disease. Our results also demonstrated fewer statements related to the physical-self, the social-self and the psychological-self, and more statements related to self-cessation in AD participants than in controls. These findings suggest that AD patients are highly preoccupied by the idea of death when thinking about the future of their self.