{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:01:18Z","timestamp":1790611278314,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Neurodegenerative diseases are among the most consequential disorders of later life, not only because of their increasing prevalence, rising from approximately 1\u20132% at age 65 to over 30% by age 85, but also because they develop within the broader clinical context of ageing, multimorbidity, frailty, and polypharmacy. In older adults, these conditions rarely present as isolated and static diagnostic entities; rather, they unfold as dynamic clinical trajectories involving the progressive interaction of cognitive decline, behavioural-neuropsychiatric symptoms, and extrapyramidal-motor dysfunction. In this review, we propose a trajectory-based framework for the interpretation and management of major neurodegenerative disorders in later life, including Alzheimer\u2019s disease, frontotemporal dementia, Parkinson\u2019s disease and Parkinson\u2019s disease dementia, dementia with Lewy bodies, and vascular cognitive impairment. Building on a conceptual model organized around three major symptom spheres: cognitive, behavioural-neuropsychiatric, and extrapyramidal-motor, we argue that each disorder can be understood according to the relative predominance and temporal evolution of these domains. Alzheimer\u2019s disease is typically cognition-led, frontotemporal dementia behaviour-led, and Parkinsonian syndromes motor-led, whereas dementia with Lewy bodies shows early multidomain convergence across all three spheres simultaneously. Vascular and mixed dementias follow more heterogeneous trajectories shaped by lesion burden, network disruption, and copathology. This framework has direct implications for diagnosis, prognostic stratification, and treatment selection, because interventions targeting one sphere may destabilize another and generate prescription cascades, delirium, or functional decline. We further discuss how biomarker-based diagnosis, disease-modifying therapies, non-pharmacological interventions, multidisciplinary care, deprescribing strategies, and palliative planning can be integrated within a trajectory-based approach. Interpreting neurodegeneration through clinical trajectories rather than diagnostic labels alone offers a more realistic and therapeutically useful model for precision geriatric neurology across the full course of disease.<\/jats:p>","DOI":"10.3390\/life16050827","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Trajectories\u00a0of Neurodegenerative Diseases in Older Adults: A Three-Sphere Framework for Precision Geriatric Neurology"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-5173","authenticated-orcid":false,"given":"Crescenzo","family":"Testa","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0444-603X","authenticated-orcid":false,"given":"Francesco","family":"Palmese","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Ravenna Campus, 48123 Ravenna, Italy"},{"name":"Internal Medicine Unit Addressed to Frailty and Aging, Department of Primary Health Care, \u201cS. Maria Delle Croci\u201d Hospital, AUSL Romagna, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Boni","sequence":"additional","affiliation":[{"name":"Geriatric Unit, AUSL Romagna, 48018 Faenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Domenicali","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Ravenna Campus, 48123 Ravenna, Italy"},{"name":"Internal Medicine Unit Addressed to Frailty and Aging, Department of Primary Health Care, \u201cS. Maria Delle Croci\u201d Hospital, AUSL Romagna, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5287-9972","authenticated-orcid":false,"given":"Fulvio","family":"Lauretani","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"},{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Ravenna Campus, 48123 Ravenna, Italy"},{"name":"Internal Medicine Unit Addressed to Frailty and Aging, Department of Primary Health Care, \u201cS. Maria Delle Croci\u201d Hospital, AUSL Romagna, 48121 Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"GBD 2019 Ageing Collaborators (2022). 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