Frontotemporal dementia: Clinicopathological correlations
Open accessAbstract
Objective: Frontotemporal lobar degeneration (FTLD) is characterized by impairments in social, behavioral, and/or language function, but postmortem studies indicate that multiple neuropathological entities lead to FTLD. This study assessed whether specific clinical features predict the underlying pathology. Methods: A clinicopathological correlation was performed on 90 consecutive patients with a pathological diagnosis of frontotemporal dementia and was compared with an additional 24 cases accrued during the same time period with a clinical diagnosis of FTLD, but with pathology not typically associated with frontotemporal dementia. Results: Postmortem examination showed multiple pathologies including tauopathies (46%), FTLD with ubiquitin‐positive inclusions (29%), and Alzheimer's disease (17%). The pathological groups manifested some distinct demographic, clinical, and neuropsychological features, although these attributes showed only a statistical association with the underlying pathology. FTLD with ubiquitin‐positive inclusions was more likely to present with both social and language dysfunction, and motor neuron disease was more likely to emerge in these patients. Tauopathies were more commonly associated with an extrapyramidal disorder. Alzheimer's disease was associated with relatively greater deficits in memory and executive function. Interpretation: Clinical and neuropsychological features contribute to delineating the spectrum of pathology underlying a patient diagnosed with FTLD, but biomarkers are needed that, together with the clinical phenotype, can predict the underlying neuropathology. Ann Neurol 2006;59:952‐962
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Personality changes are more common in patients with bvFTD than fvAD, with differences in the nature of the personality change shedding light on the underlying diagnosis.
“Personality changes are more common in patients with bvFTD than fvAD, with differences in the nature of the personality change shedding light on the underlying diagnosis [10, 22].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [10]
The Results describe early personality changes in the frontal or social/dysexecutive variant of FTLD, and the Discussion says early clinical features can help distinguish pathological subgroups statistically. But the Results do not establish that personality changes are more common in bvFTD than in frontal-variant AD or identify differing types of personality change between them; they report that behavioral/social dysfunction alone was not significantly different among the pathological groups. Our copy provides no page numbers for these passages. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe proportion of fvAD is likely higher because AD pathology can be found in up to 25% of patients with a clinical diagnosis of bvFTD.
“although this figure is likely higher because AD pathology can be found in up to 25% of patients with a clinical diagnosis of bvFTD [9, 10].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [10]
The Discussion reports AD pathology in 16.7% of patients clinically diagnosed with FTLD, supporting the general point that AD can underlie a frontotemporal clinical presentation. It does not give a rate of up to 25% specifically for behavioral-variant FTD (bvFTD), and it does not establish that the proportion of frontal-variant AD is higher. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe presence of svPPA and FTD-ALS shows a strong correlation with TDP-43 pathology.
“The presence of svPPA and FTD‐ALS show a strong correlation with TDP‐43 pathology.”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [25]
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Frontotemporal dementia and related disorders: Deciphering the enigma
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Review: neuropathology of non-tau frontotemporal lobar degeneration
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Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention
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Self-citationAcetylated Tau Neuropathology in Sporadic and Hereditary Tauopathies
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Self-citationNeurocognitive contributions to verbal fluency deficits in frontotemporal lobar degeneration
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Self-citationReduced CSF p-Tau <sub>181</sub> to Tau ratio is a biomarker for FTLD-TDP
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Self-citationAntemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND
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Self-citationClinicopathologic differences among patients with behavioral variant frontotemporal dementia
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Csf p-tau<sub>181</sub>/tau ratio as biomarker for TDP pathology in frontotemporal dementia
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Longitudinal decline in autopsy-defined frontotemporal lobar degeneration
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Self-citationA 2-Step Cerebrospinal Algorithm for the Selection of Frontotemporal Lobar Degeneration Subtypes
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Biomarkers in frontotemporal lobar degenerations—Progress and challenges
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Self-citationDiagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road
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“Personality changes are more common in patients with bvFTD than fvAD, with differences in the nature of the personality change shedding light on the underlying diagnosis [10, 22].”
BackgroundAtypical Alzheimer Disease Variants
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Self-citationThe Use of Profanity During Letter Fluency Tasks in Frontotemporal Dementia and Alzheimer Disease
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- Authors
- Forman, M. S., Farmer, J., Johnson, J. K., Clark, C. M., Arnold, S. E., Coslett, H. B., Chatterjee, A., Hurtig, H. I., Karlawish, J. H., Rosen, H. J., Van Deerlin, V., Lee, V. M. ‐., Miller, B. L., Trojanowski, J. Q., & Grossman, M.
- Affiliations
- University of Pennsylvania (US)
- University of California, San Francisco (US)
- Corresponding author
- Grossman, Murray
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2006-05-22
- Volume
- 59
- Issue
- 6
- Pages
- 952-962
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC2629792
- OpenAlex
- W2098399185
- Cited by
- 478
- References
- 57
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 13 · 2023: 16 · 2022: 10 · 2021: 14 · 2020: 15 · 2019: 17 · 2018: 13 · 2017: 18 · 2016: 15 · 2015: 17 · 2014: 23 · 2013: 28 · 2012: 37
- FWCI
- 30.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01-AG09215, R01-AG15116, P30AG10124, P01 AG-17586, K08 AG20073, P30AG010124, P01AG009215, R01AG015116, P01AG017586, R01AG022538, K08AG020073, P01-AG19724, L30 AG024692, P01AG019724)
- National Institute of Neurological Disorders and Stroke (R01-NS44266, K08 NS41408, K08NS041408, R01NS044266)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- frontotemporal dementia, frontotemporal lobar degeneration, clinicopathological correlation, tauopathy, Alzheimer's disease, motor neuron disease, extrapyramidal disorders, memory impairment, executive dysfunction, neuropathology, biomarkers
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Inclusion Bodies, Dementia, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neuropsychological Tests, Thiazoles, Age of Onset, Neurodegenerative Diseases, Tauopathies, Ubiquitin, Benzothiazoles
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