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Abstract

Frontotemporal degeneration (FTD) is an umbrella term encompassing a range of rare neurodegenerative disorders that cause progressive declines in cognition, behavior, and personality. Hearing directly from individuals living with FTD and their care partners is critical in optimizing care, identifying meaningful clinical trial endpoints, and improving research recruitment and retention. The current paper presents a subset of data from the FTD Insights Survey, chronicling the diagnostic journey, symptoms, and the impact of FTD on distress, quality of life, and independence, in the mild to moderate stages of the disease. Survey respondents included 219 individuals diagnosed with FTD and 437 current care partners, representing a range of FTD diagnoses. Around half of survey respondents reported seeing three or more doctors before an FTD diagnosis was given, and a range of prior diagnoses were noted. Most frequently endorsed symptoms tended to be consistent with clinical characteristics of the specific diagnosis, though there was significant variability in symptoms reported within diagnostic categories as well as considerable overlap in symptoms between diagnostic categories. Cognitive and language symptoms of FTD were generally most distressing to the person diagnosed, and a loss of independence was endorsed as affecting quality of life. The distinct perspectives of diagnosed persons and care partners regarding disease impact differed notably for bvFTD/Pick’s disease. Participating independently in a range of activities, within the home, outside the home, and with other people, were reported as challenging for people living with FTD, underscoring the degree to which the lives of these individuals are affected even at the mild and moderate stages of disease. Overall, by heeding the perspectives of those living with FTD, we can begin to design more meaningful research studies, provide better care, and develop therapies that improve quality of life.

Keywords

frontotemporal degeneration frontotemporal dementia survey lived experience

Introduction

As experts on the lived experience of a disease, the perspectives of people diagnosed and their loved ones are key to consider in clinical research. Engaging persons diagnosed and their care partners in clinical research design has both practical and ethical benefits, including the identification of clinical trial endpoints that are meaningful for participants and their care partners, more positive participant research experiences, improved clinical trial recruitment and retention, and enhanced financial value for sponsors.¹ Within the United States, the past decade has seen changes to regulatory and legal requirements for such input. A leading framework is the 2014 FDA Roadmap to Patient-Focused Outcome Measurement in Clinical Trials, which includes (1) understanding the disease or condition, (2) conceptualizing treatment benefit, and (3) selecting/developing outcome measures.²

Hearing directly from those impacted by a medical condition is even more crucial in rare diseases, where fundamental information about the diagnostic journey, most troublesome symptoms, disease impact, and efficacy of existing interventions may be less defined. It may also prove more difficult to document change in the domains relevant to patients, as needed for orphan drug regulatory approval. Heterogeneity in symptom manifestation, inadequate information about the natural course of the disease, potential inability for patients to report on their own condition, and a lack of familiarity on the part of healthcare providers can all lead to misconceptions about what matters most to people with lived experience.³ Based on the FDA’s Roadmap to Patient-Focused Outcome Measurement in Clinical Trials, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Emerging Good Practices for Outcomes Research Task Force Report further outlined challenges specific to developing appropriate outcomes in rare disease research and highlighted solutions such as focusing on symptoms that are most common or most impactful based on patient perspective, better understanding of disease progression despite limited data, and working with patient advocacy organizations and registries to solicit patient and care partner input.⁴

Frontotemporal lobar degeneration (FTLD) refers to a group of neuropathological disease processes that generally target the frontal and temporal cortices of the brain. FTLD is associated with a range of different clinical disorders or phenotypes, and here we use the term “frontotemporal degeneration” (FTD) to refer to this group of related, rare neurodegenerative disorders. FTD disorders typically involve some degree of cognitive and behavioral dysfunction, sometimes with concomitant motor disturbances. FTD phenotypes include:

• Behavioral variant FTD (bvFTD), more commonly known as behavioral variant frontotemporal dementia, characterized by personality changes, apathy, and a progressive decline in appropriate social behavior, judgment, self-control, and empathy.

• Primary progressive aphasia (PPA), a primary impairment of language, in which one may lose the ability to speak, read, write, and understand others’ speech. PPA is further broken down into nonfluent/agrammatic variant (nfvPPA), semantic variant (svPPA), and logopenic variant (lvPPA), based on the specific language dysfunction.

• FTD with amyotrophic lateral sclerosis (FTD-ALS), in which FTD and ALS co-occur with both motor neuron and cognitive symptoms.

• Corticobasal degeneration (CBD), in which brain regions associated with initiating, controlling, and coordinating movement are also impacted. Corticobasal syndrome (CBS) is a clinical phenotype associated with CBD.

• Progressive supranuclear palsy (PSP), which primarily affects movement, such as balance, walking, and coordination.

While initially individuals may present with symptoms primarily consistent with one of these FTD phenotypes, over the course of the illness additional functional domains are impacted, ultimately leading to death. FTD disorders have a median onset in midlife and vary in clinical presentation, pathology, and etiology; however, diagnoses are typically made based on clinical manifestation. The heterogeneity of symptoms, which overlap with other neurodegenerative and psychiatric conditions; the absence of established biomarkers; and a lack of awareness of this young-onset dementia can lead to years of misdiagnosis.^5-7 Epidemiologists estimate the prevalence of the FTD disorders in the United States at approximately 60,000, however, this figure is widely believed to be an underestimation given challenges with accessing timely, accurate diagnoses and lack of awareness of the diagnostic criteria or tests.^8,9

While the experience of living with and caring for people with dementia, particularly Alzheimer’s disease, has been documented, there is little literature on the lived experience of FTD. Research in this area tends to focus specifically on caregiver burden or the experience of a single FTD disorder (e.g.^10-16

To better understand the breadth of experience of FTD and inform clinical trial design from a patient- and care partner-centered perspective, The Association for Frontotemporal Degeneration and the FTD Disorders Registry collaborated on the FTD Insights Survey, the largest data source to-date on community experiences with FTD. This article represents the first scientific publication from this dataset. It will report a subset of the data collected from the FTD Insights Survey, documenting the lived experiences of those in the mild to moderate clinical stages of the disease as it relates to diagnostic journey, symptoms experienced, impact of the disease, and, briefly, use of treatments.

Method

Participants

Individuals currently diagnosed with any FTD spectrum disorder, as well as biological relatives and care partners (current or past) of individuals with FTD, were invited to participate in the FTD Insights Survey between October 2020 and March 2021. In total, 1796 respondents completed the survey, including 219 diagnosed individuals, 338 biological relatives who are not (or were not) care partners, and 1238 current or past care partners who may or may not be relatives (one participant who could not be assigned relative status was removed from the dataset). In the current analyses, we included all data from survey respondents diagnosed with FTD. In order to focus on the lived experiences of the early to mid-stages of disease, we excluded all data from past care partners (i.e., care partners of those who are now deceased), and current care partners who indicated that the diagnosed individual with FTD was severely or profoundly functionally impaired (i.e., only those with mild or moderate functional impairment were included). Impairment was categorized by asking care partners how they would describe the current level of functioning of the person diagnosed: mild (needs little supervision to perform daily activities), moderate (needs supervision to perform most daily activities), severe (needs full supervision to perform nearly all daily activities), or profound (can no longer perform daily activities and has limited mobility and ability to communicate). We also excluded all data from biological relatives who are not care partners as they did not answer the survey questions relevant to the current investigation. Thus, the maximum number of participants included in the analyses below was N = 656 (219 diagnosed individuals [33%], 437 current care partners [67%]). Importantly, one diagnosed individual’s experience could be represented by multiple survey respondents (e.g., a person diagnosed with FTD completed the survey, and their care partner also completed the survey). Results presented in this paper reflect responses from persons diagnosed about their own experiences as well as responses from care partners about the experience of the person with FTD. The study participants represented a range of self-reported FTD diagnoses: 395 (60%) with bvFTD or Pick’s disease; 155 (24%) with PPA, including 21 nfvPPA, 41 svPPA, 26 lvPPA, and 67 PPA with no subtype known; 61 (9%) with PSP or CBS; 13 (2%) with FTD in the context of ALS; and 32 (5%) with an unknown diagnosis. Only individuals living in the United States, United Kingdom, or Canada were eligible to participate. Demographic information of the individuals with FTD represented in the survey (as reported by themselves or by their care partner), including age, sex, education, race/ethnicity, and country of residence, are available in Table 1.

Table 1.

Demographics of the individuals with FTD represented in the survey.

Demographic	N (%)
Age in years (M [SD])	66.5 [9.1]
Sex
Male	413 (63%)
Female	242 (37%)
Education*
Doctoral degree	42 (7%)
Master’s degree	154 (25%)
Bachelor’s degree	206 (33%)
Associate’s degree	80 (13%)
High school diploma	128 (21%)
Elementary or middle school	6 (1%)
Race or ethnicity
White/Caucasian	603 (92%)
Hispanic/Latinx	11 (2%)
East Asian	8 (1%)
Black/African American/African British	12 (2%)
American Indian or Alaskan Native	4 (<1%)
Middle Eastern	2 (<1%)
Indian	0 (0%)
Native Hawaiian or Pacific Islander	0 (0%)
Other	7 (1%)
More than one race	3 (<1%)
Prefer not to answer	3 (<1%)
Country of residence
USA	589 (90%)
Canada	28 (4%)
UK	35 (5%)
Self-reported diagnosis
bvFTD or Pick’s disease	395 (60%)
Diagnosed individuals	103
Care partners	292
PPA	155 (24%)
Diagnosed individuals	49
Care partners	106
PSP or CBS	61 (9%)
Diagnosed individuals	43
Care partners	18
FTD with ALS	13 (2%)
Not sure	32 (5%)

Note. Data from individuals with a current FTD diagnosis answering for themselves, and current/past care partners answering about the individual with FTD. *= education data from USA and Canadian residents only. Percentages calculated with number of participants who opted to answer the question as the denominator.

Survey Design

The FTD Insights Survey included a total of 191 questions, but not all participants answered all questions. Rather, the survey used branching and skip logic based on responses to previous questions. The main points of branching were based on whether the respondent was (1) an individual diagnosed with FTD, (2) a biological relative of someone diagnosed who is not a care partner, (3) deemed to be at biological risk of developing FTD, (4) a current care partner of someone diagnosed with FTD, or (5) a past care partner for someone with FTD who is now deceased. There were 36 questions that required answers in order to progress through the survey, 13 of which were slightly reworded replicates depending on the respondent (i.e., diagnosed person vs care partner).

The development of the survey was guided by The Association for Frontotemporal Degeneration and the FTD Disorders Registry, with input from experts in the field of FTD including clinicians and researchers. Core survey elements were derived from existing surveys designed and used by the FTD Disorders Registry. Pilot testing among the intended respondents was used to refine and finalize the FTD Insights Survey. Survey questions captured demographic information, family history of FTD, the diagnostic journey, symptoms experienced, distress regarding symptoms, independence and quality of life, past experiences with treatments, hopes for future treatments, and perspectives on research participation and clinical trials. For the current paper, we focus only on survey questions relating to the following themes/topics: the diagnostic journey, including the number of doctors seen prior to FTD diagnosis and any previous diagnoses; symptoms experienced, including cognitive, behavioral, psychiatric, motor, and sleep disturbances; and disease and treatment impact, including distress related to symptoms, disease impact on quality of life and independence, and the impact of past treatments.

Diagnostic Journey

Survey questions included “Prior to being diagnosed with FTD, was a different diagnosis given?”, and the response of “yes” would trigger a list of potential other diagnoses for the participant to select all that applied, including ALS, Alzheimer’s disease, anxiety, bipolar disorder, depression, Lewy Body disease, menopause, mid-life crisis, mild cognitive impairment, Parkinson’s disease, schizophrenia, stroke, vascular disease, other psychiatric diagnosis, other diagnosis, and “I’m not sure”. The survey also asked “How many different doctors were consulted before an FTD diagnosis was made?”, with response options including 1 or 2, 3 or 4, 4 or 5, more than 5, or “I’m not sure”.

Symptom Domains

Survey questions included “How would you describe the first indication that something was wrong?” and “Since the first symptom(s), what other symptoms have developed?”. Both questions allowed the respondent to select as many of the following as applied: language (e.g., speaking, finding words, understanding, knowing the meaning of objects); memory (e.g., remembering recent events, learning new information); thinking (e.g., solving problems, making judgments, organizing); spatial (e.g. judging distances, perceiving objects); personality (e.g., acting differently or inappropriately in a social situation); relationships (e.g., getting along with others); mood (e.g., anxious, not interested, depressed, irritable, emotional outbursts); eating/drinking (e.g., cravings, alcohol intake, weight gain); behavior (repetitive or compulsive behavior, rigid routines); sleep (e.g., not sleeping through the night, bad dreams, sleeping too much), delusions/hallucinations, a specific difficulty in everyday life, other, and “I’m not sure”.

Disease and Treatment Impact

The survey included the following questions relating to disease and treatment impact: “What symptoms, if any, distress [the person with FTD] the most?”, “What effect(s) of having FTD has had the most significant impact on the overall quality of life [of the person diagnosed?] (select up to three)”, “Do symptoms make it difficult for [the person diagnosed with FTD] to do any of the following activities independently? (select all that apply)”, “Do symptoms make it difficult for [the person diagnosed with FTD] to do any of the following activities outside of the home independently? (select all that apply)”, “Do symptoms make it difficult for [the person diagnosed with FTD] to do any of the following activities involving others? (select all that apply)”. All response options can be found in Tables 4 through 9. Regarding treatment impact, the survey included the question “Is there a treatment (medication or other) that has had the most positive impact on [the person with FTD’s] life?”, with response options including yes, no, and “I’m not sure”.

Procedure

The FTD Insights Survey was available online from October 9, 2020, through March 31, 2021. Survey responses were anonymous; no identifying information was collected. The survey link was promoted in newsletter notices, social media posts, and email invitations to The Association for Frontotemporal Degeneration and the FTD Disorders Registry constituent lists. Advertising materials were also disseminated to allied patient advocacy organizations. The survey was deemed to have “exempt” status by an Institutional Review Board (IRB) for data collection in the United States and Canada. Data collection in the United Kingdom was permitted under an existing research study protocol of the Genetic Frontotemporal dementia Initiative (GENFI) and was executed by special invitation. Geographic restrictions were largely based on a combination of survey design (i.e., language, pre-testing, geographic relevance of response options) and IRB factors. Further adaptions for language or geographic scope were outside the parameters of the current study.

Statistical Analyses

All survey data can be requested from the FTD Disorders Registry at https://ftdregistry.org/for-researchers. All frequencies were calculated using custom scripts in Python version 3.6. For ease of presentation, and based on broad phenotypic similarity across individual diagnoses, survey response frequencies were calculated for three overarching diagnostic categories: (1) bvFTD and Pick’s diseases; (2) PPA (all subtypes); and (3) PSP and CBS. Within these diagnostic categories, responses from diagnosed individuals and care partners were pooled, unless otherwise stated. Individuals with FTD-ALS were not included in the diagnostic category breakdowns, due to low numbers precluding meaningful interpretation of the data (N = 13). Percentages based on frequencies were calculated with the number of respondents who answered the specific survey question as the percentage denominator. Unanswered survey questions were coded as missing data. Note that survey responses cannot be interpreted as entirely independent as individuals with FTD may be represented by themselves and their care partners in separate survey responses. There was no way to account for this in analysis due to the anonymous nature of the survey.

Results

Diagnostic Journey

Table 2 presents the diagnostic journey survey results. Prior to being diagnosed with FTD, a different diagnosis was given to 259 (40%) of the individuals with FTD represented in the survey. This included 44% of those diagnosed with bvFTD/Pick’s disease, 26% of those with PPA, and 43% of those with PSP/CBS. Of those who received a different prior diagnosis, the most common in individuals who ultimately received a bvFTD/Pick’s disease diagnosis was depression (54%), followed by Mild Cognitive Impairment (38%) and anxiety (35%). In individuals who ultimately received a PPA diagnosis, the most common prior diagnosis was Alzheimer’s disease (37%), followed by anxiety (32%) and depression (32%). Of those who received another diagnosis prior to a PSP/CBS diagnosis, the majority (85%) were diagnosed with Parkinson’s disease. Across all diagnostic phenotypes, approximately half (49%) of people with FTD saw 3 or more doctors before an FTD diagnosis was given, though this varied among phenotype: 35% for PPA, 54% for bvFTD/Pick’s disease, and 59% for PSP/CBS.

Table 2.

Results of the survey questions relating to the diagnostic journey.

	bvFTD/Pick’s disease	PPA	PSP/CBS
Prior to being diagnosed with FTD, was a different diagnosis given?
No	208 (53%)	110 (71%)	33 (54%)
Yes	171 (44%)	41 (26%)	26 (43%)
Not sure	14 (4%)	4 (3%)	2 (3%)
If yes, what other diagnoses were given? (Select all that apply.)
ALS/Lou Gehrig’s disease or motor neuron disease	0 (0%)	0 (0%)	0 (0%)
Alzheimer’s disease	35 (20%)	15 (37%)	0 (0%)
Anxiety	59 (35%)	13 (32%)	0 (0%)
Bipolar disorder (manic depressive disorder)	35 (20%)	3 (7%)	0 0 (%)
Depression	93 (54%)	13 (32%)	1 (4%)
Lewy Body disease/dementia	10 (6%)	0 (0%)	1 (4%)
Menopause	9 (5%)	4 (10%)	0 (0%)
Mid-life crisis	16 (9%)	1 (2%)	0 (0%)
Mild cognitive impairment	65 (38%)	11 (27%)	0 (0%)
Parkinson’s disease/parkinsonism	6 (4%)	0 (0%)	22 (85%)
Schizophrenia	9 (5%)	0 (0%)	0 (0%)
Stroke	6 (4%)	1 (2%)	2 (8%)
Vascular disease/dementia	13 (8%)	0 (0%)	0 (0%)
Other psychiatric diagnosis	16 (9%)	1 (2%)	0 (0%)
Other	35 (20%)	4 (10%)	5 (19%)
I’m not sure	1 (<1%)	2 (5%)	0 (0%)
Number of doctors consulted before an FTD diagnosis was made
1 or 2	176 (45%)	100 (65%)	24 (39%)
3 or 4	130 (33%)	40 (26%)	26 (43%)
4 or 5	39 (10%)	8 (5%)	6 (10%)
More than 5	41 (10%)	6 (4%)	4 (7%)
Not sure	6 (2%)	1 (1%)	1 (2%)

Symptom Domains

Table 3 presents the survey results pertaining to experiences across different symptom domains. Information on the specific symptoms reported within each domain is beyond the scope of this paper. As expected, the experiences of symptom domains differed across diagnostic groups. In the bvFTD/Pick’s group, over 80% of survey respondents, including both persons diagnosed and care partners, reported the person diagnosed experiencing problems with thinking (92%), memory difficulties (83%), personality changes (86%), and mood changes (80%). Language problems were also commonly reported (72%). In the PPA group, unsurprisingly the vast majority reported language problems (99%), although thinking problems (75%) and memory difficulties (74%) were also frequently endorsed. In the PSP/CBS group, motor problems (e.g., tremor, balance, performing movements) were the most commonly reported symptom domain, though the majority also reported language changes (70%) and mood disturbances (66%). Spatial impairments were the least common cognitive symptom across all three diagnostic groups but were most common in the PSP/CBS group (43%) and least common in the PPA group (18%). Relationship and behavioral changes were most frequently reported in the bvFTD/Pick’s disease group (58-67%) but were also endorsed by those with PPA (26-36%) and PSP/CBS (21-23%). Delusions and hallucinations were relatively less frequently reported than other symptom domains, but were present across the diagnostic groups, most commonly in bvFTD/Pick’s disease (29%) and least often in PPA (13%).

Table 3.

Overview of symptoms experienced and the first indication of something wrong.

	bvFTD/Pick’s Disease (N=395)	PPA (N = 155)	PSP/CBS (N = 61)
Symptoms experienced
Language	283 (72%)	153 (99%)	43 (70%)
Memory	327 (83%)	114 (74%)	30 (49%)
Thinking	363 (92%)	116 (75%)	31 (51%)
Spatial	138 (35%)	28 (18%)	26 (43%)
Personality	338 (86%)	65 (42%)	22 (36%)
Relationships	227 (57%)	41 (26%)	13 (21%)
Mood	316 (80%)	76 (49%)	40 (66%)
Motor	163 (41%)	33 (21%)	58 (95%)
Eating	245 (62%)	57 (37%)	12 (20%)
Behavior	265 (67%)	56 (36%)	14 (23%)
Sleep	227 (57%)	58 (37%)	32 (52%)
Delusions or hallucinations	113 (29%)	20 (13%)	13 (21%)
I’m not sure	16 (4%)	8 (5%)	4 (7%)
First indication something was wrong
Language	112 (28%)	135 (87%)	13 (21%)
Memory	182 (46%)	51 (33%)	10 (16%)
Thinking	267 (68%)	62 (40%)	13 (21%)
Spatial	54 (14%)	6 (4%)	10 (16%)
Personality	280 (71%)	23 (15%)	11 (18%)
Relationships	163 (41%)	16 (10%)	8 (13%)
Mood	229 (58%)	27 (17%)	21 (34%)
Motor	58 (15%)	12 (8%)	41 (67%)
Eating	114 (29%)	17 (11%)	5 (8%)
Behavior	157 (40%)	15 (10%)	4 (7%)
Sleep	114 (29%)	19 (12%)	9 (15%)
Delusions or hallucinations	52 (13%)	1 (1%)	3 (5%)
I’m not sure	3 (1%)	1 (1%)	1 (2%)

Note. Raw numbers with percentages in parentheses. For both questions, survey respondents were allowed to select all that apply. Percentage denominator is the number of participants who selected at least one response. Language = e.g., speaking, finding words, understanding, knowing the meaning of objects. Memory = e.g., remembering recent events, learning new information. Thinking = e.g., solving problems, making judgments, organizing. Spatial = e.g., judging distances, perceiving objects. Personality = e.g., acting differently or inappropriately in a social situation. Relationships = e.g., getting along with others. Mood = e.g., anxious, not interested, depressed, irritable, emotional outbursts. Eating/drinking = e.g., cravings, alcohol intake, weight gain. Behavior = e.g., repetitive or compulsive behavior, rigid routines; Sleep = e.g., not sleeping through the night, bad dreams, sleeping too much. Other response options included “Other” and “A specific difficulty in everyday life”, which were free text responses.

The first indication that something was wrong, as reported by persons diagnosed and care partners, also differed across diagnostic phenotypes. For those with bvFTD/Pick’s disease, the most frequently reported first symptom domain was a change in personality (71%), followed by problems with thinking skills (68%), and mood disturbances (58%). Within the PPA group, language difficulties were the most commonly reported first indication of something wrong (87%), though more than a third noted problems with thinking (40%) or memory (33%) as the first symptom. Around two thirds of individuals with PSP/CBS endorsed motor changes as the first symptom domain affected (67%), but a third reported initial mood disturbances (34%).

Disease and Treatment Impact

Results on disease impact are presented separately by diagnostic groups as above (i.e. pooled across diagnosed individuals and care partners), and then by diagnosed individuals vs care partner responses for those with reported bvFTD/Pick’s disease. The distinct perspectives of diagnosed persons and care partners was important for bvFTD/Pick’s disease in particular because reduced awareness of symptoms (anosognosia), or a lack of concern about the impact of the disease (anosodiaphoria), are well-documented features of bvFTD¹. Other diagnostic categories were not split by respondent type due to relatively lower numbers in these groups, but also because poor awareness of symptoms is a more frequent feature of bvFTD compared to other diagnoses.^17,18 Tables 4 through 9 present the results relating to disease and treatment impact.

Table 4.

Results of the survey question that asks which symptoms of FTD distress the person with FTD the most.

	Diagnostic group			bvFTD/Pick’s Disease only
	bvFTD/Pick’s Disease (N = 395)	PPA (N = 155)	PSP/CBS (N = 60)	Diagnosed Person (N = 103)	Care Partner (N = 292)
Not distressed by symptoms	97 (25%)	19 (12%)	5 (8%)	6 (6%)	91 (31%)
Language	64 (16%)	88 (57%)	15 (25%)	13 (13%)	51 (17%)
Memory	60 (15%)	12 (8%)	4 (7%)	25 (24%)	35 (12%)
Thinking	45 (11%)	6 (4%)	4 (7%)	18 (17%)	27 (9%)
Spatial	2 (1%)	0 (0%)	0 (0%)	1 (1%)	1 (<1%)
Personality	5 (1%)	0 (0%)	0 (0%)	3 (3%)	2 (<1%)
Relationships	4 (1%)	2 (1%)	1 (2%)	1 (1%)	3 (1%)
Mood	16 (4%)	4 (3%)	4 (7%)	6 (6%)	10 (3%)
Motor	18 (5%)	2 (1%)	18 (30%)	5 (5%)	13 (4%)
Eating or drinking	9 (2%)	2 (1%)	0 (0%)	5 (5%)	4 (1%)
Behavior	4 (1%)	1 (1%)	0 (0%)	1 (1%)	3 (1%)
Sleep	13 (3%)	2 (1%)	2 (3%)	7 (7%)	6 (2%)
Delusions or hallucinations	5 (1%)	1 (1%)	0 (0%)	1 (1%)	4 (1%)
A specific difficulty in everyday life	13 (3%)	9 (6%)	4 (7%)	2 (2%)	11 (4%)
Other	24 (6%)	5 (6%)	3 (5%)	6 (6%)	18 (6%)
I’m not sure	16 (4%)	2 (1%)	0 (0%)	3 (3%)	13 (4%)

Note. Raw numbers with percentages in parentheses. Percentage denominator is the number of participants who opted to answer the question. “Other” and “A specific difficulty in everyday life” were free text responses.

In the bvFTD/Pick’s disease and PPA groups, cognitive symptoms (problems with language, memory, or thinking) were reported to be most distressing to individuals diagnosed. Of the symptom domains, language problems were by far the most distressing symptom in the PPA group (57%), followed by memory deficits (8%). For those with bvFTD/Pick’s disease, thinking, memory and language problems were reported as the most distressing symptom at 11-16% of the time. In the PSP/CBS group, motor disturbances were reported to be most distressing (30%), followed by language problems (25%). Interestingly, 31% of bvFTD care partners reported that the diagnosed individual was not distressed by their symptoms, while only 6% of diagnosed individuals reported that they were not distressed. Lack of distress was reported for 12% of people diagnosed with PPA and 8% of people diagnosed with PSP/CBS. Results are shown in Table 4.

A loss of independence due to FTD symptoms had the greatest impact on quality of life (QoL) as perceived by people diagnosed in both the bvFTD/Pick’s disease (61%) and PSP/CBS (71%) groups. By contrast, difficulty communicating affected QoL the most for persons with PPA (78%), though it also had a significant effect on QoL in those diagnosed with bvFTD/Pick’s disease (33%) and PSP/CBS (38%). A loss of identity or sense of self and the loss of a job or career impacted QoL in a quarter to a third of persons diagnosed within each diagnostic category (bvFTD/Pick’s disease = 34-36%; PPA = 30-34%; PSP/CBS = 26-31%). Unsurprisingly, reduced mobility affected QoL for the majority of those with PSP/CBS (62%), but only a minority of those with bvFTD/Pick’s disease (18%) and PPA (7%). Across all diagnostic categories, a loss of financial security was the least frequently reported effect of FTD on QoL for those diagnosed (all <10%), which may reflect the demographic of those who responded to the survey. However, notably, within the bvFTD/Pick’s disease group a loss of financial security was reported by 22% of diagnosed individuals to significantly impact their QoL, but by 0% of care partners. Likewise, anxiety about the future was reported by diagnosed individuals to impact QoL more frequently than by care partners (31% vs 18%). By contrast, a loss of family relationships was reported to significantly impact QoL by 20% of partners vs 11% of diagnosed individuals. A loss of independence was the most frequently endorsed response by both diagnosed individuals (51%) and care partners (64%) in the bvFTD/Pick’s disease group. All results are available in Table 5.

Table 5.

Results of the survey question that asks which effects of FTD have had the most significant impact on the quality of life of the person with FTD.

	Diagnostic group			bvFTD/Pick’s Disease only
	bvFTD/Pick’s Disease (N=395)	PPA (N = 155)	PSP/CBS (N = 61)	Diagnosed Person (N = 103)	Care Partner (N = 292)
Loss of identity or sense of self	134 (34%)	53 (34%)	16 (26%)	34 (33%)	100 (34%)
Loss of my job or career	143 (36%)	47 (30%)	19 (31%)	37 (36%)	106 (36%)
Loss of important family relationships	68 (17%)	21 (14%)	6 (10%)	11 (11%)	57 (20%)
Loss of friendships	68 (17%)	15 (10%)	6 (10%)	21 (20%)	47 (16%)
Loss of independence	240 (61%)	66 (43%)	43 (70%)	53 (51%)	187 (64%)
Difficulty communicating	131 (33%)	121 (78%)	23 (38%)	31 (30%)	100 (34%)
Reduced mobility	71 (18%)	10 (6%)	38 (62%)	17 (17%)	54 (18%)
Anxiety about the future	86 (22%)	34 (22%)	9 (15%)	32 (31%)	54 (18%)
Loss of financial security (retirement, savings, income)	23 (6%)	3 (2%)	6 (10%)	23 (22%)	0 (0%)
Other	20 (5%)	4 (3%)	2 (3%)	4 (4%)	16 (5%)
I’m not sure	17 (4%)	3 (2%)	0 (0%)	6 (6%)	11 (4%)

Note. The respondent is allowed to select up to three answers. Raw numbers with percentages in parentheses. Percentage denominator is the number of participants who selected at least one response.

With regard to maintaining independence, as reported by those diagnosed, paying bills or organizing financial/business files was the most frequently reported challenge for bvFTD/Pick’s disease (80%) and PPA groups (70%), whereas within the PSP/CBS group, the top challenges were preparing meals (75%) and performing household chores (73%). However, overall, the three diagnostic groups endorsed challenges across most response options, with at least 30% of persons diagnosed in each group reporting that FTD affected their ability to maintain independence performing daily hygiene, performing household chores, preparing meals, keeping track of appointments, managing medications, paying bills or organizing financial/business files, doing crafts, and managing communications. 20% of those diagnosed with PPA reported having no challenges doing the listed activities independently; this was notably lower for the bvFTD/Pick’s disease group (8%) and PSP/CBS group (10%). Within the bvFTD/Pick’s disease group, responses from diagnosed individuals and care partners were largely consistent; the main difference was that care partners endorsed difficulties maintaining independence in the listed activities more frequently than diagnosed individuals did, possibly reflecting the fact that if a diagnosed individual is self-completing the survey, they are likely to be relatively functionally independent. All results are available in Table 6.

Table 6.

Results of the survey question that asks whether symptoms make it difficult for the person diagnosed with to do any of the listed home activities independently.

	Diagnostic group			bvFTD/Pick’s Disease only
	bvFTD/Pick’s Disease (N = 394)	PPA (N = 153)	PSP/CBS (N = 60)	Diagnosed Person (N = 102)	Care Partner (N = 292)
Perform daily hygiene (shower, groom, dress)	177 (45%)	47 (31%)	35 (58%)	30 (29%)	147 (50%)
Perform household chores (laundry, vacuum, clean)	224 (57%)	65 (42%)	44 (73%)	39 (38%)	185 (63%)
Prepare a meal (cook)	261 (66%)	94 (61%)	45 (75%)	35 (34%)	226 (77%)
Keep track of appointments	289 (73%)	90 (59%)	26 (43%)	57 (56%)	232 (79%)
Manage medications	253 (64%)	73 (48%)	19 (32%)	46 (45%)	207 (71%)
Pay bills, organize financial or business files	314 (80%)	107 (70%)	36 (60%)	59 (58%)	255 (87%)
Do crafts	126 (32%)	50 (33%)	26 (43%)	22 (22%)	104 (36%)
Care for a pet	124 (31%)	33 (22%)	15 (25%)	15 (15%)	109 (37%)
Manage communications (use email, answer the phone, answer the door)	214 (54%)	93 (61%)	27 (45%)	31 (31%)	183 (63%)
I don’t have difficulties doing these activities independently	31 (8%)	31 (20%)	6 (10%)	22 (22%)	9 (3%)
Other	40 (10%)	9 (6%)	9 (15%)	6 (6%)	34 (12%)
I’m not sure	0 (0%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)

Note. The respondent is allowed to select all response options that apply. Raw numbers with percentages in parentheses. Percentage denominator is the number of participants who selected at least one response.

Maintaining independence in activities outside the home was also reported to be challenging for individuals with FTD. Over 40% (up to 75%) of individuals in each of the three diagnostic groups endorsed difficulties with working, shopping and other errands, driving, and using mass transit. The most frequently reported difficulty outside the home for individuals across all three diagnostic groups was driving a car (bvFTD/Pick’s disease = 73%, PPA = 60%, PSP/CBS = 75%). Engaging in physical activity was more commonly reported as a challenge for PSP/CBS (68%), but less so for bvFTD/Pick’s disease (43%) and PPA (26%). Again, individuals with PPA most frequently reported having no difficulties with the listed activities (26%), which was a higher percentage than the bvFTD/Pick’s group (10%) and the PSP/CBS group (8%). Within the bvFTD/Pick’s disease group, care partners again endorsed challenges with the listed activities more frequently than diagnosed individuals did. All results are available in Table 7.

Table 7.

Results of the survey question that asks whether symptoms make it difficult for the person diagnosed with to do any of the listed activities outside the home independently.

	Diagnostic group			bvFTD/Pick’s Disease only
	bvFTD/Pick’s Disease (N = 392)	PPA (N = 151)	PSP/CBS (N = 60)	Diagnosed Person (N = 101)	Care Partner (N = 291)
Attend school	83 (21%)	38 (25%)	10 (17%)	16 (16%)	67 (23%)
Work	231 (59%)	75 (50%)	26 (43%)	48 (48%)	183 (63%)
Shop for groceries, run other errands	258 (66%)	89 (59%)	43 (72%)	43 (43%)	215 (74%)
Drive a car	285 (73%)	90 (60%)	45 (75%)	65 (64%)	220 (76%)
Use mass transit	159 (41%)	70 (46%)	29 (48%)	28 (28%)	131 (45%)
Engage in physical activity (take a walk, ride a bike, exercise)	170 (43%)	39 (26%)	41 (68%)	41 (41%)	129 (44%)
No difficulties doing activities outside of the home independently	38 (10%)	39 (26%)	5 (8%)	16 (16%)	22 (8%)
Other	35 (9%)	9 (6%)	7 (12%)	8 (8%)	27 (9%)
I’m not sure	6 (2%)	2 (1%)	0 (0%)	0 (0%)	6 (2%)

Engaging in activities with others is another facet of life that individuals with FTD endorsed having difficulties in. Over 40% (up to 79%) of individuals in each of the three diagnostic groups reported having trouble playing games like cards or chess, participating in conversations, attending social or other gatherings, interacting with new people, and caring for children or grandchildren. Participating in conversations was the most highly endorsed challenge for individuals with PPA (79%), while attending gatherings was the most common challenge for those with bvFTD/Pick’s disease (69%). Individuals with PSP/CBS reported having conversations and attending gatherings as their two most frequent challenges. Being intimate with a spouse or partner was a more common challenge in bvFTD/Pick’s disease (68%) than the other two groups (PPA = 48%, PSP/CBS = 36%), as was maintaining friendships (bvFTD/Pick’s disease = 55%, PPA = 43%, PSP/CBS = 28%). Again, within the bvFTD/Pick’s disease group, care partners reported challenges engaging with others in the listed activities more frequently than diagnosed individuals, with the exception of attending social gatherings, which was slightly more commonly reported as a challenge by diagnosed individuals (72% vs 69%). All results are available in Table 8.

Table 8.

Results of the survey question that asks whether symptoms make it difficult for the person diagnosed with to do any of the listed activities with others.

	Diagnostic group			bvFTD/Pick’s Disease only
	bvFTD/Pick’s Disease (N = 392)	PPA (N = 154)	PSP/CBS (N = 58)	Diagnosed Person (N = 103)	Care Partner (N = 289)
Play a game like cards or chess	217 (55%)	85 (55%)	27 (47%)	42 (41%)	175 (61%)
Participate in conversations with family or friends	256 (65%)	121 (79%)	30 (52%)	40 (39%)	216 (75%)
Attend social or other gatherings where there will be more people	272 (69%)	101 (66%)	30 (52%)	74 (72%)	198 (69%)
Interact with new people in everyday life (in stores, on phone, etc.)	213 (54%)	97 (63%)	28 (48%)	38 (37%)	175 (61%)
Be intimate with a spouse or partner	265 (68%)	74 (48%)	21 (36%)	55 (53%)	210 (73%)
Maintain friendships	214 (55%)	66 (43%)	16 (28%)	45 (44%)	169 (58%)
Care for children or grandchildren	210 (54%)	72 (47%)	27 (47%)	27 (26%)	183 (63%)
Care for a spouse or parent*	20 (19%)	3 (6%)	13 (33%)	20 (19%)	N/A
No difficulties doing activities involving others	15 (4%)	12 (8%)	4 (7%)	12 (12%)	3 (1%)
Other	24 (6%)	4 (3%)	2 (3%)	5 (5%)	19 (7%)
I’m not sure	3 (1%)	1 (1%)	1 (2%)	0 (0%)	3 (1%)

Note. * = “caring for a spouse or parent” was not an option given in the care partner version of this question so N’s are based on diagnosed individuals only (N=103 bvFTD/Pick’s disease; N=48 PPA; N=40 PSP/CBS). The respondent is allowed to select all response options that apply. Raw numbers with percentages in parentheses. Percentage denominator is the number of participants who selected at least one response.

With regard to the impact of past treatments, the survey asked participants about a range of treatment and symptom management options, including prescription medications, over-the-counter medications, lifestyle modifications, allied health therapies (e.g., occupational therapy), and experimental research treatments (e.g., brain stimulation). The majority of persons diagnosed and care partners responding on behalf of those diagnosed, across all three diagnostic groups (59%), reported that there has not been a treatment that has had a positive impact on the diagnosed individual’s life. This was the case for 55% of the bvFTD/Pick’s disease group, 63% of the PPA group, and 63% of the PSP/CBS group. Results are available in Table 9.

Table 9.

Results showing whether any past treatment has had a positive impact on the life of the person diagnosed with FTD.

	bvFTD/Pick’s Disease (N = 390)	PPA (N = 150)	CBS/PSP (N = 60)
No	213 (55%)	95 (63%)	38 (63%)
Yes	143 (37%)	44 (29%)	19 (32%)
I’m not sure	34 (9%)	11 (7%)	3 (5%)

Note. Raw numbers with percentages in parentheses. Percentage denominator is the number of participants who opted to answer the question.

Discussion

The aim of this paper was to document aspects of the lived experience of FTD at the mild and moderate stages of disease, as reported by persons diagnosed and care partners in the FTD Insights Survey. Specifically, we sought to chronicle the experience of individuals with FTD regarding their diagnostic journey, symptoms, and past treatments, as well as the impact of the disease on quality of life and independence. This survey is the largest of its kind to date with additional questions, not reported here, related to care partner burden, specific symptom experiences, treatments, risk tolerance, genetic testing, and research readiness. Data are also available on the lived experience of FTD reported by caregivers of persons at severe stages of disease or who have passed away.

The diagnostic journey is often complicated for those with FTD and their families. Indeed, around half of our survey respondents reported seeing three or more doctors before an FTD diagnosis was made, and this was highest for the PSP/CBS group. Similarly, a 2017 web-based survey of almost 700 FTD caregivers reported that 65% saw 3 or more doctors before an FTD diagnosis was made.¹⁹ Misdiagnoses are common and a source of burden for care partners.¹⁰ Initial psychiatric diagnoses have been found to delay a correct diagnosis of FTD for up to 3-6 years,^5,7 which has implications for medication and symptom management, as well as financial and family ramifications. Although in the current dataset we could not verify the prior diagnoses as “misdiagnoses” per se, given the lack of clinical, biomarker or diagnostic information available to verify the presence of FTD, it is nevertheless informative to understand the breadth of other diagnoses that were given to individuals who subsequently received an FTD diagnosis. Psychiatric disorders were common, particularly in bvFTD and PPA, which is unsurprising as psychiatric symptoms are often part of the clinical presentation in these disorders.^20-25 By contrast, the most frequent diagnosis given to those who ultimately received a PSP or CBS clinical diagnosis was Parkinson’s disease, which is unsurprising given that both PSP and CBS are considered atypical parkinsonian disorders. Errors in an FTD diagnosis may lead to errors in treatment, with doctors prescribing medications that are ineffective or detrimental.²⁶ However, there remain multiple challenges to accurate clinical diagnosis of FTD, including a lack of established diagnostic biomarkers, and physicians’ poor familiarity with FTD(25).

The symptom domains reported are largely in line with what would be expected based on the clinical characteristics at early and moderate stages of each disorder. For example, overall, language problems were by far the most commonly endorsed symptom in those with PPA, motor symptoms were reported by the vast majority of individuals with PSP/CBS, and personality and cognitive changes were the most common symptoms in people with bvFTD/Pick’s disease. However, symptom domains varied considerably within diagnostic categories, particularly when it came to identifying initial symptoms. For example, over 25% of individuals with bvFTD/Pick’s disease endorsed changes in language, memory, thinking, personality, relationships, mood, behavior, eating, and sleep as among their initial symptoms experienced. Symptoms also heavily overlapped across diagnostic categories. For example, while language problems define PPA, over 70% of individuals with bvFTD/Pick’s disease or PSP/CBS endorsed difficulties with language. Likewise, personality, behavioral and relationship changes are pathognomonic of bvFTD/Pick’s disease, but a significant portion of those with PPA and PSP/CBS also reported changes within these domains (21-42%). While it is clear from the literature that FTD phenotypes ultimately evolve to encompass symptoms across many domains, these survey data shed light on the heterogeneous manifestations of FTD at its earliest clinical onset. Such information is often challenging to capture and to measure objectively in real time, as individuals with FTD typically are not being followed prior to disease onset unless they are part of a family with a known genetic mutation for FTD.

The symptoms found to be most distressing to the diagnosed person varied considerably both within and between diagnostic categories. Language changes were among the top two most distressing symptoms for individuals with PPA and PSP/CBS. However, the most frequently endorsed symptoms in each group were not necessarily reported to be the most distressing to the diagnosed person. For example, individuals with bvFTD/Pick’s disease reported cognitive symptoms (memory, thinking, language changes) to be most distressing, whereas personality changes, which were just as frequently experienced, tended not to be most distressing to the person diagnosed. Care partners in the bvFTD/Pick’s disease group frequently endorsed that that the diagnosed individual was not distressed by symptoms, consistent with known features of bvFTD including anosognosia, which is a lack of awareness of the disease, or “frontal anosodiaphoria”, which is a lack of concern about having the disorder.^17,27

However, patients with bvFTD do in fact report some symptoms to be distressing, with cognitive difficulties including language (13%), memory (24%) and thinking (17%) reported more frequently than changes in personality (3%), relationships (1%) and behavior (1%). A similar pattern of endorsement was observed within the care partners of patients with bvFTD (Table 4) suggesting that metacognitive capacities may vary for different types of symptoms. Indeed, impairments in elements of social cognition which are believed to underlie changes in personality, relationships, and behavior^28,29 may be more intimately linked with self-awareness^30,31 and therefore inherently less distressing than impairments in primary aspects of cognition such as memory and language that can occur in bvFTD, for example. Work examining the neuroanatomic substrates of social cognitive changes in bvFTD point to a degradation in orbitofrontal³² and ventromedial³³ regions of the prefrontal cortex (PFC), as well as the salience network,^34,35 all of which have been linked to reductions in self-awareness.³⁶

When survey participants were asked to endorse the top three effects of FTD that impacted quality of life, patterns of responses were largely consistent with the specific challenges for different diagnostic groups. For example, the majority of individuals with PPA noted that difficulty communicating affected quality of life, while those with PSP/CBS endorsed reduced mobility as impacting quality of life. Otherwise, a loss of independence was the most highly endorsed determinant of quality of life in the full sample; this suggests that strategies to maintain independence should be of utmost importance to researchers and stakeholders in the field.

In the bvFTD/Pick’s disease group, responses varied across care partners and diagnosed individuals. For example, anxiety about the future and a loss of financial security were both reported by diagnosed individuals to affect their quality of life, but were rarely noted by care partners. This indicates that the source of the information is critical to consider when devising strategies to improve the quality of life for people with FTD. Whether these differences reflect reliable differences across care partners and persons diagnosed would need to be validated in studies with dyad pairs, as it could be due here to a responder bias where the persons diagnosed who were able and willing to complete the survey represent a highly functioning subset of those affected.

As aforementioned, losing independence was reported to significantly affect the quality of life of people living with FTD. When asked which activities within the home were challenging to continue performing independently, the results were striking in how commonly almost all the listed response options were endorsed. These findings emphasize the importance of home-based intervention strategies to maintain independence, such as keeping a calendar, introducing phone alert reminder systems, installing safety switches on cooking appliances, and so on.

Likewise, maintaining independence in multiple different activities outside the home and participating in various activities with other people were endorsed as difficult for people with FTD. The relatively high rates of endorsement across different activities call attention to the significant degree to which the lives of people with FTD are affected even at mild and moderate stages of disease. In addition, the variability within and between diagnoses suggest that strategies or interventions should be tailored to the specific challenges of the individual, and that phenotype alone is not sufficient for determining intervention targets. The crucial need to develop interventions and treatments that may positively affect the lives of people with FTD was underscored by the survey results showing a half to two thirds of participants have not found any existing treatment to have a positive impact.

Clinical trialists that seek to monitor the effect of a treatment on patient-centered outcomes will need to address the heterogeneity of both symptoms and priorities within and across FTD disorders with shared underlying etiology. They will also need to address the issues of anosognosia and frontal anosodiaphoria, where the person diagnosed may not be aware of or distressed by their own symptoms, despite significant decline in function, independence, and family well-being, even at early stages of disease.

While these survey results are informative, several limitations need to be taken into account. Survey respondents are not necessarily representative of the broader community of those affected by FTD. The vast majority of participants identified as white/Caucasian, with extremely limited representation from other racial and ethnic groups. This is an ongoing problem in all biomedical research with specific challenges for FTD research³⁷ that are beginning to be addressed. Survey respondents were also more likely to have achieved higher-than-average levels of education. Respondents were restricted to the United States, Canada, and the United Kingdom. We can anticipate that many perspectives were missing from the survey, particularly from communities that may have less access to resources and healthcare specialists. Survey responses of persons diagnosed may reflect a relatively high-functioning demographic of individuals with FTD who are both motivated and able to respond to a research study. Second, the diagnoses cannot be clinically confirmed and it is both possible and likely that some self-reported diagnosis are incorrect or may actually reflect undiagnosed comorbidities, such as underlying Alzheimer’s pathophysiology. Third, comparisons between the responses of care partner and persons diagnosed may need validation with dyad-based research studies, as: (a) the persons diagnosed who were able to respond to the survey likely reflect a highly-functioning, non-apathetic subset of people affected by FTD, and (b) we do not know the degree of overlap between diagnosed person and care partner responses in the current survey. Fourth, more research is needed specifically on FTD-ALS, a group excluded from most of these analyses due to the small number of respondents that would preclude meaningful interpretation of results.

Overall, the FTD Insights Survey is an invaluable tool for researchers and other stakeholders to learn from the perspectives of people diagnosed with FTD, their family members, and care partners. By understanding the lived experience of FTD, we can design more successful research studies, develop new therapies, and provide better care to improve quality of life.

Footnotes

Acknowledgments

We would like to thank all survey respondents for their time and participation. We also thank experts in the field of FTD for their input on survey development and review of survey materials: Jonathan Rohrer, Caroline Greaves, Edward Huey, Adam Boxer, and David Knopman.

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S. Cosentino: S.C. received funds from Association for Frontotemporal Degeneration to support her time for survey development, analysis, and manuscript planning.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: At the time of writing M.S.B. was supported by an FTD Insights Postdoctoral Fellowship from The Association for Frontotemporal Degeneration.

ORCID iDs

Megan S. Barker

Shana G. Dodge

Notes

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Living With Frontotemporal Degeneration: Diagnostic Journey,Symptom Experiences,and Disease Impact

Abstract

Keywords

Introduction

Method

Participants

Survey Design

Diagnostic Journey

Symptom Domains

Disease and Treatment Impact

Procedure

Statistical Analyses

Results

Diagnostic Journey

Symptom Domains

Disease and Treatment Impact

Discussion

Footnotes

Acknowledgments

Declaration of Conflicting Interests

Funding

ORCID iDs

Notes

References