BDNF‐Met polymorphism on top of amyloid pathology predisposes for faster cognitive decline in cognitively normal elderly: The SCIENCe Project: Genetics/genetic factors of Alzheimer's disease. (7th December 2020)

• Record Type: Journal Article
• Authors: van den Bosch, Karlijn Antoinette; Verberk, Inge M.W.; Ebenau, Jarith; van der Lee, Sven J.; Jansen, Iris E.; Prins, Niels D.; Scheltens, Philip; Teunissen, Charlotte E.; van Der Flier, Wiesje
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• 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.042728
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Previous studies showed that in preclinical AD, the Brain‐derived neurotrophic factor (BNDF) Val66Met polymorphism Met was related to faster decline in episodic memory. We aimed to assess the joint associations of BDNF Val66Met polymorphism and amyloid positivity with decline over time in the main cognitive domains, and with risk of incident dementia in cognitively normal adults with subjective cognitive decline (SCD). Additionally, we explored the effect of BDNF plasma levels on cognitive decline. Method: We included 688 individuals with SCD (59 ± 8y, 39%F, MMSE = 28 ± 2) from the Amsterdam Dementia Cohort (ADC) and the SCIENCe project, with repeated performance on neuropsychological tests available (average follow‐up: 1.6 ± 2.4y, median number of visits 2 ± 2, total datapoints 1660). Participants were grouped by a four‐level variable based on Met‐carrierschip (Met+) and decreased baseline CSF Abeta42 (A+), resulting in n = 39 (6%) Met+A+, n = 206 (30%) M+A‐, n = 76 (11%) Met‐A+, n = 367 (53%) Met‐A‐ (reference group). For a subgroup (n = 198) baseline plasma levels BDNF was measured by Simoa. Linear mixed models (LMM) were used to assess associations with cognitive decline. We evaluated the association with risk of dementia using Cox proportional hazard model. All analyses were adjusted for age, gender and education. Result: Compared to Met‐A‐, Met‐A+ showed a steeper decline on some tests for memory, attention and executive functioning, while Met+A+ showed steeper decline on almost all cognitive tests, covering global cognition, memory, language, attention and executive functioning (Table 1). Met+A‐ was not associated with steeper decline. Met+A+ (HR = 9.2; 95%CI: 2.9‐29.1) and Met‐A+ (HR = 6.6, 95%CI: 2.2‐19.7) were at increased risk of dementia compared to Met‐A‐ (HR – reference), whereas Met+A‐ (HR 1.3, 95%CI 0.3‐4.8) was not. Plasma levels of BDNF were not associated with cognitive decline. Conclusion: Among individuals with SCD, Met‐carriership on top of amyloid pathology is associated with faster cognitive decline over time, and associated with higher risk of dementia. These results imply that this group might benefit from more frequent clinical monitoring.