Patients With LATE Pathology More Likely to Present as Cognitively Normal

Later development of cognitive symptoms and greater longevity is more likely to occur in LATE pathology compared with AD or LATE+AD.

Patients with limbic predominant age-related TAR DNA-binding protein 43 (TDP-43; LATE) pathology were more likely to develop cognitive symptoms later and live longer compared with patients with Alzheimer disease (AD) or LATE+AD. They were also more likely to be classified as cognitively normal compared with their counterparts. These are the findings of study published in Neurology.

Among individuals age 90 years and older, LATE is thought to be the second most common neurodegenerative disease. Although the clinical and pathological changes associated with LATE were established years ago, its recognition as a distinct pathology is relatively recent. As such, little is understood about clinical symptoms and its effects on patients.

In this study, researchers sourced from the Alzheimer’s Disease Research Center (ADRC) network. Patients (N=686) who had AD and/or LATE and were age 75 years and older at death between 2005 and 2020 were evaluated for clinical and pathological characteristics. Outcomes were compared between the subset of patients with LATE (n=31), AD (n=393), and LATE+AD (n=262) pathologies.

The LATE, AD, and LATE+AD groups comprised 54.8%, 50.4%, and 52.8% women; they were aged 89.5, 85.4, and 85.7 years at death (P =.004); 87.1%, 94.7%, and 92.4% were White; and 83.9%, 40.7%, and 32.4% were apolipoprotein E4 (APOE4) negative (P <.001), respectively.

[T]here are clear differences at initial presentation between those with LATE pathology relative to those with AD pathology and comorbid AD+LATE.

Compared with the other 2 groups, the LATE group tended to have a longer disease duration (mean, 8.9 vs 7.5-7.9 years; P =.06) and they were older at initial symptom onset (mean, 78.8 vs 72.5-72.9 years; P =.002).

At the initial visit, more of the LATE group were classified as cognitively normal (41.9%; P <.001) compared with AD (25.4%) or LATE+AD (12.2%); fewer of the LATE group self-reported memory decline (45.2%; P =.007) compared with AD (66.4%) or LATE+AD (74.4%); and more of the LATE+AD group had caregiver reported memory decline (85.1%; P <.001) compared with LATE (51.6%) or AD (70.2%).

In general, for all 11 neuropsychological tests, the LATE group had the best scores, followed by the AD group and the LATE+AD group. In which, the Mini Mental State Examination (MMSE) score, for example, differed significantly between groups (F[2,620], 15.3; P <.001).

At autopsy, more patients with LATE (32.2%) or LATE+AD (27.8%) had hippocampal sclerosis compared with AD (6.1%; P <.001) and fewer patients with LATE (48.4%; P <.001) had cerebral amyloid angiopathy compared with AD (74.5%) or LATE+AD (85.4%). No group differences in microinfarcts (26.7%-32.3%), Lewy Body pathology (43.3%-49.6%), arteriolosclerosis (50.9%-65.3%), or infarcts and lacunes (71.0%-85.9%) were observed.

The limitations of this study included the cohort size imbalances and the lack of a normative comparator group.

This study found evidence that LATE differed in many clinical and pathological features from AD and LATE+AD.

Researchers concluded, “In an autopsy confirmed sample, we found that there are clear differences at initial presentation between those with LATE pathology relative to those with AD pathology and comorbid AD+LATE. Perhaps most notably, patients who are ultimately found to possess LATE pathological changes on autopsy are more likely to be classified at baseline as cognitively normal based on consensus diagnosis.”

This article originally appeared on Neurology Advisor


Pagnotti RMB, Pudmjee SB, Cross CL, Miller JB. Cognitive and clinical characteristics of patients with limbic predominant age-related TDP-43 encephalopathy. Neurology. Published online March 23, 2023. doi:10.1212/WNL.0000000000207159