Longitudinal clinical and neuropsychological outcomes in limbic predominant age related TDP_43 encephalopathy vs. Alzheimer's disease from The 90+ Study. (20th December 2022)

• Record Type: Journal Article
• Authors: Sajjadi, S. Ahmad; Qian, Tianchen; Bukhari, Syed; Woodworth, Davis C.; Montine, Thomas J.; Corrada, Maria M.; Kawas, Claudia H.
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 7
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.067366
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Limbic predominant age related TDP‐43 encephalopathy‐neuropathologic change (LATE‐NC) is prevalent in the oldest old. Our aim was to determine the association of longitudinal change in clinical and neuropsychological measures in relation to the presence of LATE‐NC and Alzheimer's disease neuropathologic change (ADNC) in an exclusively oldest‐old cohort. Methods: 323 participants from The 90+ Study with longitudinal evaluations and autopsy data were studied. LATE‐NC was considered present in those with TDP‐43 in hippocampus and/or neocortex and ADNC in those with high‐likelihood ADNC according to NIA‐AA guidelines. Scores in clinical dementia rating sum of the boxes (CDR‐SB) and neuropsychological tests representing global cognition (MMSE and modified MMSE (3MS)), memory (California verbal learning test‐long delay (CVLT)), language (Boston naming test (BNT)), executive function (TRAIL‐B), attention/concentration (digit span backward), and orientation (from MMSE) were used to calculate standardized effect sizes (SES) of LATE‐NC and ADNC on longitudinal change in the scores. Relationships were estimated using linear mixed effect models accounting for age at death, age at the time of testing, sex, and education. Results: Mean age at death was 97.7 years and 67% were female. Prevalence of LATE‐NC and ADNC in the whole cohort was 28% and 31% respectively and 11.4% had both pathologies. Of 34% who had dementia at death, 42.7% had LATE‐NC and 41.8% had ADNC (Table 1). LATE‐NC alone was associated with decline in global measures [MMSE (SES: ‐0.70), 3MS (SES:‐0.77), CDR‐SB score (SES: 0.89)] and with orientation (SES: ‐0.82). In contrast, ADNC alone was associated with decline in executive function‐ TRAILB (SES: 0.49). Both pathologies, LATE‐NC and ADNC, were related to decline in memory‐CVLT (SES: 0.73 for LATE‐NC & 0.46 for ADNC), language‐BNT (SES: 0.54 for LATE‐NC & 0.45 for ADNC), and attention‐digit span backward (SES: 0.41 for LATE‐NC & SES: 0.36 for ADNC) (Figure 1). Conclusion: Our results confirm the importance of LATE‐NC in the oldest old and highlight that LATE‐NC and ADNC are associated with partially distinct patterns of clinical and neuropsychological decline that might aid prediction of LATE‐NC during life.