Suicidal Behavior in Alzheimer’s Disease: A Preliminary Study

Abstract

Background: Suicidal behavior presents a significant dilemma in the context of Alzheimer’s disease. Numerous ethical discussions have emerged regarding euthanasia for patients suffering from neurodegenerative conditions, and research indicates an elevated incidence of suicide in the early stages of dementia. However, there remains a gap in knowledge concerning the historical prevalence of suicidal ideations or attempts among individuals diagnosed with Alzheimer’s disease. This study aims to investigate the historical patterns of suicidal behavior and the associated factors across the lifespan in patients with Alzheimer’s disease. Methods: This study is an excerpt from a case–control research study, where the sample size was calculated at 150 participants, with 75 in the case group and 75 in the control group. Here, the descriptive statistics for the first third of the sample, 50 participants, are discussed. Results: Among the participants in the case group, 12.5% reported having suicidal ideation throughout life, compared to 24% in the control group (OR for suicidal ideation = 0.432 [0.095–1.966]). Additionally, among the participants in the case group, 4% reported having attempted suicide at some point in their life, compared to 8% in the control group (OR for suicide attempts = 0.479 [0.41–5.652]). People with Alzheimer’s disease tended to have a worse quality of life but less suicidality. Conclusions: It appears that suicidal behavior is inversely related to the risk of developing suicidal intentions. The odds ratio data demonstrate the need for a larger sample size to determine whether there is a difference in the history of suicide throughout the lives of people with Alzheimer’s disease and among the general population.

1. Introduction

Alzheimer’s disease (AD) has been one of the most studied illnesses in medical science in the last century. Even so, many of its mechanisms remain a mystery, such as the real causes that trigger the neurodegenerative process [1]. It is known that many factors are associated with the biological processes that lead to cellular apoptosis in dementia. Among these, genetic characteristics and cardiovascular diseases stand out [2,3].

Other mental disorders, such as depression, have been linked to the onset of dementia caused by AD [4]. One significant aspect associated with severe depression is suicidal behavior [5]. However, suicidality remains a largely under-researched topic. A meta-analysis of 12 studies examining suicidal behavior in dementia found that individuals with vascular dementia were significantly more likely to experience suicidal ideation (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.06; 3.8) and attempt suicide (OR = 1.94, 95% CI = 1.28; 2.94) compared to those with AD, though there was no significant difference in mortality by suicide (OR = 1.05, 95% CI = 0.69; 1.59). Additionally, individuals with dementia with Lewy bodies were significantly more likely to report suicidal ideation (OR = 1.56, 95% CI = 1.09; 2.23) than those who did not report significantly higher rates of suicidal ideation (OR = 1.65, 95% CI = 0.5; 5.46) [6].

In order to delve deeper into the connections between the two conditions, a further analysis was performed of the key factors that emerged from initial analysis, these being the role of depression, which often accompanies cognitive decline, and the presence of the e4 allele of apolipoprotein E, which has been associated with an increased risk of AD. These findings highlight the complex interplay between neurodegeneration and mental health, underscoring the importance of addressing both issues in clinical settings [7].

Currently, there is a notable absence of research focusing on the historical context of suicidal behavior among individuals diagnosed with AD. The primary objective of this study is to delve into and analyze the patterns of suicidal behavior experienced by these patients, as well as to assess their overall quality of life. By exploring these critical aspects, the study seeks to contribute valuable insights to the understanding of the psychological and emotional challenges faced by those living with AD.

2. Materials and Methods

2.1. Source Population

The participants in this study were selected from a pool of 11,739 patients treated at a psychogeriatrics outpatient clinic in São Paulo, Brazil. Out of these patients, 568 were diagnosed with AD between 2016 and 2024.

This study is a preliminary result of case–control research, with a total sample of 150 participants. It included the first third of the cases and controls (η = 50).

2.2. Sample Size

The prevalence of AD among the elderly has been measured at 1.6% [8]. If we consider a sampling error of 2% with a 95% confidence level, we will have a η of 150.

- The formula for calculating the sample size is as follows:

$$\mathsf{\eta }={\displaystyle \frac{\frac{Z^2}{2}·\mathrm{p}·\mathrm{q}}{E^2}}$$

where η is the sample size, Z²/2 is the critical value for the desired degree of confidence (1.96), p (0.016) is the proportion of favorable results of the variable in the population, q (0.984) is the proportion of unfavorable results in the population (q = 1 − p), and E (0.02) is the standard error.

2.3. Diagnostic Criteria

Cases were defined as elderly individuals (people over 65 years of age) with AD. Controls were elderly individuals (people over 65 years of age) without a diagnosis of AD. The AD diagnosis was made by the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association [NINCDS-ADRDA] [9]. All participants underwent a diagnostic battery, including the Rey Auditory Verbal Learning Test (RAVLT), the Cambridge Cognitive Examination—Revised (CAMCOG-R), and the Alzheimer’s Disease Assessment Scale—Cognitive (ADAS-cog) [10,11,12]. The diagnosis of AD was certified by the DSM-V TR criteria [13]. Brain magnetic resonance imaging (MRI) or computerized tomography (CT) scans were performed to confirm hippocampal atrophy. Blood tests were performed to rule out other causes of cognitive disorders, such as vitamin B12 and folic acid deficiency. The severity of AD was classified, according to the Clinical Dementia Rating [CDR], into minimal, intermediate, mild, moderate, and severe [14]. Individuals recruited with severe dementia classification were excluded. Remote memory was assessed by observing individuals’ recognition of photos of 5 famous Brazilian individuals from recent decades. Those who did not recognize at least three were excluded.

2.4. Instruments

Interpersonal variables were measured using Flanagan’s Quality of Life Scale (QoLS) and the Suicidal Behavior-Associated Facts Questionnaire (SAF-quest). Both instruments are validated in Portuguese [15,16]. The feasibility of both questionnaires was assessed in a pilot study with health controls [17].

2.5. Study Design

The case–control study was meticulously designed to evaluate the history of suicidal behavior and the overall quality of life among patients diagnosed with AD, while drawing comparative insights from a cohort of healthy control subjects. The investigation encompassed a total of 150 participants and was executed in two distinct phases, each of which was integral to the study’s objectives.

2.5.1. Clinical Phase

In the initial phase, participants underwent a comprehensive clinical evaluation paired with advanced neuroimaging analyses. This thorough assessment was crucial in establishing a clinical diagnosis based solely on observable symptoms and behavioral indicators associated with Alzheimer’s disease (AD). Notably, at this stage, no biomarker testing was conducted, as the focus was primarily on conducting clinical observations and examining imaging results to characterize the disease’s presentation.

Initially, a pilot study was conducted with twenty participants from the control group to verify the possibility of using the instruments with elderly people [17]. Subsequently, a study of the adequacy of the instruments was carried out on 25 participants in the case group [18]. Next, we present here the evaluation of the first third of the data, for 25 participants in the case group and 25 participants in the control group.

2.5.2. Biomarker Phase

The second phase of the study introduced an examination of blood biomarkers associated with AD in all participant samples. This phase aimed to substantiate the clinical diagnoses made in patients who exhibited symptoms consistent with the AD criteria. The diagnostic confirmation hinged upon the ATN classification system to categorize the presence of key pathological features: ‘A’ signifies the presence of beta-amyloid plaques, ‘T’ represents the detection of tau protein tangles, and ‘N’ indicates evidence of neurodegeneration. This two-phased approach allowed researchers to holistically evaluate both the psychological and physiological aspects of AD, providing a comprehensive understanding of its impact on individuals’ lives [19]. This phase of the study investigated the presence of significant differences in suicidal behavior among asymptomatic individuals who tested positive for biomarkers associated with AD. By exploring these aspects, the research enhances our comprehension of the relationship between AD and suicidal tendencies.

2.6. Data Analysis

Qualitative data are presented in tables. Continuous variables are summarized as means and SDs; categorical variables are summarized as frequencies and proportions. Data from the participants are presented in tables to detail their characteristics. All analyses were carried out using IBM Corp., released in 2023. IBM SPSS Statistics for Windows, Version 29, Armonk, NY, USA: IBM Corp.

3. Results

A flow chart of the study participants is shown in Figure 1. The study recruited 147 65-year-old individuals treated at the psychogeriatrics outpatient clinic at Unimed Bauru. Out of these, 25 were included in the case group because they met the diagnostic criteria for AD; 25 were included in the control group; 20 were included in the pilot study (17); and 25 were included in the adequacy study (19) [18]. Eight participants were excluded because they met severe CDR criteria; another five were excluded due to significant hearing difficulties; and two were excluded because they lacked recognition of at least three famous Brazilian people. Another 37 individuals did not agree to participate. All the included participants understood the questionnaires.

The demographic and clinical characteristics of the participants are summarized in

Table 1. Demographic and clinical characteristics of participants.

Characteristic	Alzheimer’s (n = 25)	Control (n = 25)	p-Value
Age (Mean ± SD)	82.6 ± 8.0	76.6 ± 6.0	0.003 *
% Female	64%	64%	1.000
% Married	48%	56%	0.757
% Living Alone	44%	24%	0.269
% High School Education or Less	100%	88%	0.231
% Unemployed	92%	88%	1.000
% Financial Difficulties	12%	8%	1.000
% Chronic Illness	84%	12%	<0.001 *
% Alcohol/Drug Use	0%	0%	-
% Heroic Behavior	4%	12%	0.602
% Heterosexual	100%	96%	1.000
% Has Children	96%	88%	0.602

* Statistically significant (p < 0.05).

. The Alzheimer’s group was significantly older than the control group (82.6 ± 8.0 years vs. 76.6 ± 6.0 years, p = 0.003). In total, 64% of the participants were women and 52% were married, and the mean age was 79.58 (±7.61). As expected, the prevalence of chronic illnesses was significantly higher in the Alzheimer’s group (84% vs. 12%, p < 0.001). Other demographic factors, such as sex distribution, marital status, living situation, education level, employment status, financial difficulties, alcohol/drug use, heroic behavior, and having children, were similar between the two groups (all p > 0.05).

3.1. Suicidal Behavior and Ideation

In the case group, 12.5% of participants had experienced suicidal ideation throughout their life, compared to 25% in the control group (OR for suicidal ideation = 0.432 [95% CI: 0.095–1.966]). Additionally, in the case group, 4% participants had attempted suicide at some point in their life, compared to 8% in the control group (OR for suicide attempts = 0.479 [95% CI: 0.41–5.652]); see Figure 2 and Figure 3, and

Table 2. Suicidal behavior and ideation.

Characteristic	Alzheimer’s (n = 25)	Control (n = 25)	OR (95% CI)
% Suicidal Ideation	12.5%	25%	0.432 (0.095–1.966)
% Suicide Attempts	4%	8%	0.479 (0.41–5.652)
% Would Consider Suicide in a Difficult Situation	16%	8%	2.1 (0.44–10.64)

.

While these findings suggest a trend towards lower rates of suicidal ideation and attempts in the Alzheimer’s group, the differences are not statistically significant, likely due to the small sample size. Interestingly, when asked if they would consider suicide in a hypothetical difficult situation, 16% of those in the Alzheimer’s group and 8% of those in the control group answered affirmatively.

3.2. Psychiatric Diagnoses

The prevalence of psychiatric diagnoses is shown in

Table 3. Psychiatric diagnoses.

Diagnosis	Alzheimer’s (n = 25)	Control (n = 25)	OR (95% CI)
Depression	24%	4%	7.67 (0.84–70.36)
GAD	4%	0%	-
Bipolar	4%	0%	-
PTSD	4%	0%	-
Borderline	4%	0%	-
Vascular Dementia	4%	0%	-
Panic	0%	0%	-
Schizophrenia	0%	0%	-

. Depression was more common in the Alzheimer’s group (24% vs. 4%), although this difference did not reach statistical significance (OR: 7.67, 95% CI: 0.84–70.36). Other psychiatric diagnoses, including generalized anxiety disorder, bipolar disorder, post-traumatic stress disorder, borderline personality disorder, and vascular dementia, were rare in both groups, each with a prevalence of 4% or less in the Alzheimer’s group and 0% in the control group.

3.3. Quality of Life

Quality of life scores, as measured by Flanagan’s Quality of Life Scale (QoLS), are presented in

Table 4. Quality of life (QoLS) scores.

QoLS Domain	Alzheimer’s (n = 25)	Control (n = 25)	p-Value
Material Comfort	5.9 ± 1.2	6.7 ± 0.6	0.006 *
Health	2.9 ± 1.5	5.9 ± 1.3	<0.001 *
Relationship with Relatives	5.4 ± 1.3	6.3 ± 1.2	0.022 *
Having a Family	6.4 ± 1.0	6.4 ± 1.0	0.834
Intimate Relationship	4.6 ± 2.0	5.8 ± 1.6	0.031 *
Close Friends	4.4 ± 1.9	5.4 ± 1.5	0.049 *
Helping Others	4.0 ± 1.3	4.8 ± 1.3	0.044 *
Public Participation	4.0 ± 1.3	5.0 ± 1.4	0.022 *
Learning	4.4 ± 1.4	5.8 ± 1.5	0.003 *
Self-Knowledge	4.2 ± 1.5	5.4 ± 1.5	0.011 *
Work	4.0 ± 1.3	5.6 ± 1.6	<0.001 *
Creative Communication	4.1 ± 1.4	5.4 ± 1.4	0.003 *
Active Recreation	3.9 ± 1.5	5.4 ± 1.4	<0.001 *
Entertainment	5.6 ± 1.2	6.3 ± 0.8	0.016*
Socialization	4.2 ± 1.6	5.4 ± 1.5	0.010 *
Total QoLS Score	68.1 ± 11.7	84.4 ± 9.4	<0.001 *

* These variables demonstraded significant difference statistics between the groups.

. The Alzheimer’s group had significantly lower scores across multiple domains compared to the control group. These domains included material comfort (p = 0.006), health (p < 0.001), relationship with relatives (p = 0.022), intimate relationships (p = 0.031), close friends (p = 0.049), helping others (p = 0.044), public participation (p = 0.022), learning (p = 0.003), self-knowledge (p = 0.011), work (p < 0.001), creative communication (p = 0.003), active recreation (p < 0.001), entertainment (p = 0.016), and socialization (p = 0.010). The total QoLS score was also significantly lower in the Alzheimer’s group (68.1 ± 11.7 vs. 84.4 ± 9.4, p < 0.001).

3.4. Other Relevant Factors

Table 5. Other relevant factors.

Factor	Alzheimer’s (n = 25)	Control (n = 25)	p-Value
% Religious	88%	92%	1.000
% Believe in Afterlife	84%	92%	0.602
% Talked About Suicide	12%	16%	1.000
% Childhood Trauma	28%	16%	0.478
% Parent Died by Suicide	4%	0%	1.000
% Sibling Attempted Suicide	8%	0%	0.490

summarizes other factors that could be associated with suicidal behavior. No significant differences were found between the groups in terms of religiosity (88% in Alzheimer’s group vs. 92% in control group, p = 1.000), belief in the afterlife (84% vs. 92%, p = 0.602), or having talked about suicide with someone (12% vs. 16%, p = 1.000). Childhood trauma was reported more frequently in the Alzheimer’s group (28% vs. 16%), but this difference was not statistically significant (p = 0.478). A history of a parent dying by suicide was present for 4% of individuals the Alzheimer’s group and no individuals in the control group (p = 1.000), while 8% of the Alzheimer’s group and no individuals in the control group had a sibling who had attempted suicide (p = 0.490).

Neither the cases nor the controls demonstrated high patterns of suicidality. All patients in the control group had some other mental disorder, while some of the cases had only AD as a neuropsychiatric disorder.

4. Discussion

This preliminary study explored the intriguing relationship between lifetime suicidal behavior and AD. Our findings, while limited by the small sample size, suggest potential differences in the historical patterns of suicidal ideation and attempts between individuals with Alzheimer’s and the control group. We also found significant differences in quality of life, as well as a higher prevalence of reported childhood trauma in the Alzheimer’s group.

Contrary to the initial hypothesis that individuals with AD might exhibit higher rates of suicidal behavior, our results indicate a trend towards lower rates of both suicidal ideation (12.5% vs. 25%) and attempts (4% vs. 8%) compared to the control group. However, these differences did not reach statistical significance. This aligns with some previous research suggesting that the cognitive impairments associated with AD, particularly in executive functioning and planning, may hinder an individual’s ability to formulate and execute a suicide plan [20,21].

Interestingly, while historical suicidal behavior appeared to be less frequent, a higher proportion of individuals with Alzheimer’s (16% vs. 8%) indicated that they might consider suicide in a hypothetical difficult life situation. This could be related to several factors. First, individuals in the early stages of Alzheimer’s, as was the case for those included in our sample, may retain insight into their declining cognitive abilities and the potential future burden on their families, leading to increased distress and contemplation of suicide as an escape [22]. Second, the significantly lower quality of life scores in the Alzheimer’s group across multiple domains, including health, social relationships, and engagement in activities, may contribute to a sense of hopelessness and a greater willingness to consider suicide in the face of adversity.

The higher prevalence of reported childhood trauma in the Alzheimer’s group (28% vs. 16%), although not statistically significant, is noteworthy. Childhood trauma is a well-established risk factor for suicidal behavior across the lifespan [23]. Early-life adversity may have a long-term impact on emotional regulation and coping mechanisms, potentially increasing vulnerability to suicidal ideation in the context of AD. However, further research with larger samples is needed to confirm this association and explore the underlying mechanisms.

Our findings add to the growing body of literature on suicide in dementia, which has yielded mixed results. Some studies have reported an increased risk of suicide in individuals with dementia, particularly in the early stages [24]. In contrast, others have found no significant difference, or even a decreased risk, compared to the general population [25]. These discrepancies may be attributed to differences in study populations, diagnostic criteria, assessment methods, and the stage of dementia being investigated.

We acknowledge several limitations in our study. First, the small sample size (n = 50) limited the statistical power to detect significant differences and increased the risk of Type II error (false negatives). Therefore, the observed trends, particularly the lower rates of suicidal ideation and attempts in the Alzheimer’s group, should be interpreted with caution. Second, the cross-sectional design prevented us from establishing temporal relationships or causality between AD and suicidal behavior. It is possible that pre-existing factors, such as personality traits or coping styles, may influence both the risk of developing Alzheimer’s disease and the likelihood of experiencing suicidal ideation. Third, our assessment of suicidal behavior relied on retrospective self-report, which may be subject to recall bias, particularly in individuals with cognitive impairment. However, we attempted to mitigate this by excluding individuals with severe dementia and using validated questionnaires. Fourth, our control group, while matched for some demographic characteristics, may not fully represent the general population, as these participants were also recruited from a psychogeriatric outpatient clinic.

Despite these limitations, our study provides valuable preliminary data and highlights several important directions for future research. Larger, prospective studies are needed to confirm the observed trends and further explore the complex interplay between AD, suicidal behavior, and associated factors. Future research should also investigate the role of specific cognitive deficits, such as impaired decision-making or impulsivity, in influencing suicide risk in dementia. Additionally, studies examining the impact of interventions aimed at improving quality of life, managing depression, and providing social support in individuals with AD may shed light on potential strategies for suicide prevention in this vulnerable population. It would also be beneficial to explore the ethical considerations surrounding end-of-life decisions and advance directives in individuals with neurodegenerative diseases, considering their capacity for decision-making and their expressed wishes.

5. Conclusions

These preliminary data suggest an inverse relationship between suicidal behavior and the prevalence of AD, such that patients with AD may experience lower rates of suicidal thoughts and actions. These intriguing findings underscore the need for more comprehensive and extensive studies that incorporate larger sample sizes, thereby enhancing the reliability and validity of the results.

Expanding the research framework is essential in order to thoroughly investigate the potential differences in suicidal behavior history among those diagnosed with AD compared to the general population throughout their lives. Such comprehensive examinations will shed light on the intricate mental health challenges faced by these two distinct groups, allowing for a better understanding of their unique psychological landscapes. There appear to be significant differences in the quality of life of cases compared to controls, but these preliminary data are limited to the issuance of an adequate opinion.

Ultimately, gaining deeper insights into this issue can pave the way for the development of more effective intervention strategies that are explicitly tailored to meet the diverse needs of individuals dealing with AD, as well as those within the broader community. By addressing these complex issues, we can better support both populations, fostering improved mental health outcomes.