Consideration of specific depressive symptom profiles may be predictive of certain neurodegenerative disease (NDG) syndromes in their early stages, thus helping to improve diagnostic sensitivity and provide more individualized patient care, according to a study results published in Frontiers in Neurology.

Recognizing that depressive symptoms are often comorbid with NDG, the researchers sought to examine patterns of self-reported depressive symptomatology in a cohort of patients with early NDG who had distinct clinically diagnosed neurodegenerative syndromes. In this observational, cross-sectional study, a total of 564 participants self-reported their symptoms of depression via use of the Geriatric Depression Scale (GDS)—a 30-item self-report questionnaire with “yes/no” responses. Total scores on the GDS range from 0 to 30, with scores between 0 and 9 considered to signify mild to moderate depression. The GDS was divided into subscales that represented 5 distinct symptoms: (1) dysphoria, (2) hopefulness, (3) withdrawal, (4) worry, and (5) cognitive concerns.

453 of the participants had been diagnosed with 1 of 6 NDGs and were in the early stages of the disease, whereas 111 were healthy older controls. Overall, of the 453 participants with NDGs, 1 of the following 6 disorders was present: (1) Alzheimer’s disease (AD) in 186 participants; (2) behavioral variant frontotemporal dementia (bvFTD) in 76 patients; (3) semantic variant primary progressive aphasia (svPPA) in 52 individuals; (4) nonfluent variant primary progressive aphasia (nfvPPA) in 46 participants; (5) progressive supranuclear palsy syndrome (PSPS) in 49 patients; and (6) corticobasal syndrome (CBS) in 44 individuals.

All participants in the NDG groups had significantly elevated measures of disease severity
(P <.001), compared with healthy controls, based on the Mini Mental Status Examination score, as well as on the CDR® Dementia Staging Instrument—a semistructured interview that gauges functional impairment across 6 domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. For each question in each of the domains, function scores are based on a 5-point Likert scale, with scores ranging from 0 to 4, with 0 denoting none, 0.5 denoting very mild, 1 denoting mild, 2 denoting moderate, and 3 denoting severe.

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Patients with PSPS exhibited significantly higher scores across all depressive symptom subscales compared with healthy controls (P <.00908). Hopelessness and withdrawal scores were significantly higher in the PSPS group than in all other NDG participant groups. Patients with PSPS had higher dysphoria scores than those with nfvPPA or AD. Those in the PSPS arm also had significantly higher cognitive concerns scores than those in the bvFTD and nfvPPA arms. Additionally, greater hopelessness, higher withdrawal, and lower worry all significantly predicted being in the PSPS group (P <.001, P <.005, and P <.05, respectively).

Although patients with CBS also presented with a hopeless, dysphoric, and withdrawn pattern, their symptoms were less severe than the participants with PSPS. The profile of patients with svPPA was characterized by worry as a key symptom, whereas individuals with AD presented only with elevated cognitive concerns. The accuracy of depressive profiles in predicting an NDG diagnosis varied between 70% and 84%.

The researchers concluded that future studies are warranted that observe patients throughout their disease course, in order to establish how these profiles change. Evaluation of mechanisms associated with these distinct symptom profiles will not only elucidate the clinical presentation of patients with NDGs, but it may also reveal key insights into the normal etiology of certain symptoms of depression in other groups of patients.


Shdo SM, Ranasinghe KG, Sturm VE, et al. Depressive symptom profiles predict specific neurodegenerative disease syndromes in early stages [published online May 29, 2020]. Front Neurol. doi: 10.3389/fneur.2020.00446