Long‐term memory over 1‐week and markers of brain pathology in cognitively unimpaired individuals from a Colombian cohort with autosomal dominant Alzheimer’s disease

  1. Ezama, Laura 3
  2. Chen, Kewei 2
  3. Vila‐Castelar, Clara 1
  4. Baena, Ana Y. 4
  5. Martinez, Jairo E. 1
  6. Aduen, Paula 1
  7. Munera, Diana 1
  8. Noriega, Daisy 1
  9. Langella, Stephanie 1
  10. Ramirez‐Gomez, Liliana A. 1
  11. Lopera, Francisco 4
  12. Quiroz, Yakeel T. 14
  1. 1 Massachusetts General Hospital, Harvard Medical School, Boston, MA USA
  2. 2 Banner Alzheimer’s Institute, Phoenix, AZ USA
  3. 3 Universidad de La Laguna, La Laguna Spain
  4. 4 Grupo de Neurociencias de Antioquia, Universidad de Antioquia, Medellin Colombia
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Revista:
Alzheimer's & Dementia

ISSN: 1552-5260,  1552-5279

Año de publicación: 2023

Volumen: 19

Número: S2

Tipo: Artículo

DOI: 10.1002/ALZ.068124 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Alzheimer's & Dementia

Resumen

BackgroundLong-term forgetting (LTF) over days or weeks may be a sensitive early marker of Alzheimer’s disease (AD), useful for preclinical AD trials. We examined associations between LTF and markers of brain pathology in individuals from the world’s largest kindred with autosomal dominant AD due to the Presenilin-1 (PSEN1) E280A mutation.MethodsA total of 14 cognitively unimpaired PSEN1 mutation carriers (mean age: 35.9 years) and 16 matched non-carriers (mean age: 32.8 years) from the Colombia-Boston Biomarker Study of autosomal dominant AD were included. Participants underwent amyloid (11-C Pittsburgh compound B) and tau (Flortaucipir) PET imaging, and memory tasks (NEUROPSI word list, stories and semi-complex figure). We examined performance on learning and delayed recall after a 20-min, 1-day and 7-day interval. LTF was calculated for the three tasks as the proportion of material retained at 20 min that was recalled 7 days later. Mann-Whitney tests were conducted to compare memory performance and LTF between PSEN1 mutation carriers and non-carriers. Spearman’s correlations were used to examine the association between LTF and brain pathology markers of amyloid burden and regional tau (entorhinal and inferior temporal cortices). Fisher’s exact tests were used to compare correlation coefficients between groups.ResultsLearning did not differ between carriers and non-carriers. Compared to non-carriers, carriers had lower 20-min recall in all three tasks (p<0.05), and lower 1-day and 7-day recall of word list and stories. There were no group differences in word list, stories or figure LTF. Further, no group differences were observed in the association of amyloid burden and LTF on any of the tasks. Lower word list LTF was associated with greater entorhinal burden among carriers, and the strength of this association was significantly different between carriers and non-carriers (p = 0.046; carriers: r = 0.73, p = 0.003; non-carriers: r = 0.43, p = 0.094).ConclusionsOur preliminary findings show that, while rates of LTF over 7 days did not differ between PSEN1 carriers and non-carriers, carriers had lower verbal memory recall over 1 and 7 days. Further, LTF was associated with early tau accumulation, suggesting that longer recall intervals may be more sensitive to detect subtle memory changes in cognitively unimpaired individuals at risk for AD.