DOI: 10.1002/alz.078514 ISSN: 1552-5260

Characteristics of oldest‐old individuals with ‘Pure’ Limbic‐predominant age‐related TDP‐43 encephalopathy: a 90+ Study case series

Zarui A. Melikyan, Anne‐Marie C Leiby, Kiana Alexis Scambray, Hannah L. Nguyen, Farheen Basith, Shahrzad Fakhraee, Syed A. Bukhari, Thomas J. Montine, María M. M. Corrada, Claudia H. Kawas, S. Ahmad Sajjadi
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) is an important contributor to dementia at age 90+. Given the high prevalence of multiple pathologies in the oldest old, the prevalence of ‘pure’ LATE and its clinical and cognitive features are poorly understood. The aims of this report are: (1) to determine the prevalence of ‘pure’ LATE among participants of The 90+ Study and (2) to describe clinical and cognitive features of ‘pure’ LATE.


Individuals for this report were identified from a total of 364 consecutive autopsies of The 90+ Study . We compared medical histories and cognition in three groups: those with ‘pure’ LATE, ‘pure’ Alzheimer’s disease neuropathologic change (ADNC), and ‘pure’ primary age‐related tauopathy (PART). ‘Pure’ LATE was defined as TDP‐43 in the hippocampus or neocortex, no moderate/severe ADNC, and no limbic/cortical Lewy bodies. ‘Pure’ ADNC group was defined as moderate/severe ADNC, no TDP‐43, and no limbic/cortical Lewy bodies. ‘Pure’ PART group was defined as limbic/cortical phosphorylated tau inclusions (Braak tau stage ≥2), no amyloid (A score = 0 and C score = 0), no TDP‐43, and no limbic/cortical Lewy bodies. All groups had <2 microvascular lesions.


LATE pathology was prevalent in the cohort (36%) but only 5 participants (1.4%) had ‘pure’ LATE. ‘Pure’ LATE group was on average older at death, more educated, and had lower proportion of women (Table) compared to the other two groups. Duration of cognitive impairment was longest and dementia was more prevalent in ‘pure’ LATE (6 years, 80%) compared to ‘pure’ ADNC (3 years, 43%) and ‘pure’ PART (3 years, 22%). Memory and executive function were more frequently impaired in ‘pure’ LATE compared to the other two groups (Table). Furthermore, histories of cardiovascular disease, syncope, depression, and extrapyramidal signs were more common, whereas osteoarthritis was less common, in ‘pure’ LATE compared to the other two groups (Table).


Given the high prevalence of multiple pathologies, ‘pure’ LATE is a relatively rare finding in the oldest old. Identifying differences between ‘pure’ LATE and other dementia related neuropathologies in this case series, may provide valuable insight to inform proper ante‐mortem diagnosis of LATE.

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