Introduction Frontotemporal dementia (FTD) compromises a group of clinically and pathologically heterogeneous neurodegenerative syndromes including two forms of primary progressive aphasia (PPA) – nonfluent aphasia and semantic dementia (SD). While language impairments are the most prominent and impairing initial symptom, over time additional disabilities accumulate as these illnesses progress, eroding quality of life and increasing the burden of care. Little is known about the chronology of acquiring non-language functional disabilities in PPA. The primary aim of this study is to describe the chronology of functional disabilities in PPA, and to examine temporal associations between psychiatric comorbidities and specific disabilities. Methods Data are from subjects enrolled in the National Alzheimer's Coordinating Center (NACC) database between June 2005 and May 2019. We included subjects whose recent diagnosis was PPA. Functional status was coded as a binary variable for the following functions: ambulation (gait and falls), transaction skills (shopping, taxes, and bills), verbal communication, meal preparation, and self-care. Descriptive statistics and cox proportional hazard analyses were used to characterize the emergence of disabilities and their association with medical and psychiatric comorbidities. Results We enrolled 1,944 subjects, comprising 91 with a CDR score of zero at baseline who were used in our analysis. Mean age of this population at baseline was 68.8 years and 43.5% were males. At the onset of the study, no individuals had impairments in self-care, while 7% had impairments in the transactions domain, 3% in ambulation, and 2% in meal preparation. Ninety-three percent had language impairments at the onset of the study, and all by 4 years. By 5 years, 41% of patients had impairments in ambulation and in self-care, 49% were impaired with respect to meal preparation and 70% had impairment in transactions. The presence of psychosis was associated with an increased risk for self-care impairment (HR 5.0, CI [2.4-10.6], p Conclusions We provide a preliminary estimation in a large sample of the year-by-year frequency of functional disability in PPA patients. Impairment in communication skills appear early, followed closely by impairment in transactions. Ambulation, self-care and meal preparation impairments occur later. A number of psychiatric symptoms were significantly associated with functional disability progression, suggesting the potential of forestalling disability progression by treating psychiatric symptoms. These findings, when fully developed, can be expected to provide clinicians with practical guidance for forecasting disabilities in their patients, providing a rational basis for targeted interventions, individualized programs of care, and care giver education and training. Funding The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA-funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG062428-01 (PI James Leverenz, MD) P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P30 AG062421-01 (PI Bradley Hyman, MD, PhD), P30 AG062422-01 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P30 AG062429-01(PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P30 AG062715-01 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD).
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Jan 1, 2024
Adam Eckart 
Open Access