Behavioral correlates of cerebrospinal fluid concentrations of aminoacids and monoamine metabolites according to APOE-ɛ4 carrier status in dementia with Lewy bodies compared with Alzheimer’s dementia and cognitively healthy people (P4.190)

Objective: To study associations of cerebrospinal fluid aminoacids and monoamine metabolites with behavior in dementia with Lewy bodies (DLB) compared with Alzheimer’s dementia (AD) and cognitively healthy people.

Background: Brain monoamine activity and aminoacid concentrations may correlate with behavioral features, reflecting their metabolism in dementia.

Design/Methods: Consecutive outpatients with probable DLB (fourth consensus report of the DLB Consortium) were paired with outpatients with late-onset AD (NIA-AA criteria) by gender, Clinical Dementia Rating (CDR) and Mini-Mental State Examination scores, and with cognitively healthy controls by gender and age (±1 year). Genotyping for rs7412/rs429358 was undertaken with TaqMan® Real-Time PCR technology. Cerebrospinal fluid concentrations of aminoacids (aspartate, glycine, glutamine, glutamate, taurine, GABA) and monoamine metabolites (HVA, 5-HIAA, VMA, MHPG, L-DOPA) were assessed by reverse-phase high-performance liquid chromatography, and correlated with Neuropsychiatric Inventory (NPI) domains.

Results: Twenty DLB participants (77.00±9.0 years-old, CDR sum-of-boxes 10.15±3.7, NPI 48.25±22.4, nine APOE-ɛ4 carriers) were paired with twenty AD participants (80.35±5.9 years-old, CDR sum-of-boxes 9.43±3.5, NPI 24.45±11.8, nine APOE-ɛ4 carriers) and twenty controls (77.15±9.0 years-old, CDR sum-of-boxes 0.25±0.5, NPI 11.00±10.1, three APOE-ɛ4 carriers). Aminoacids and the HVA/5-HIAA ratio were associated with apathy, dysphoria, or both in AD and DLB. Associations for APOE-ɛ4 carriers: lower levels of HVA, 5-HIAA, glutamate and taurine in DLB (p<0.05); glutamine with night-time disturbances (p<0.001); aspartate, glycine and the HVA/5-HIAA ratio with hallucinations in DLB (p<0.03); GABA, aspartate, glycine, glutamine and taurine with anxiety in AD (p<0.04). Associations for APOE-ɛ4 non-carriers: higher levels of glutamate in AD than in DLB (p=0.002); GABA and taurine with hallucinations and agitation in DLB (p<0.01); GABA, aspartate, glycine and glutamate with anxiety in DLB (p<0.0001); aspartate and glycine with night-time disturbances in DLB (p<0.001); VMA with dysphoria, delusions and night-time disturbances in AD (p<0.03). Levels of monoamine metabolites were unaffected by pharmacotherapy.

Conclusions: Neurotransmitter dysfunction may differentially affect behavioral phenotypes in dementia syndromes.

Study Supported by:

FAPESP (grant #2015/10109-5)

Disclosure: Dr De Oliveira has nothing to disclose. Dr. Miraldo has nothing to disclose. Dr. Castro has nothing to disclose. Dr. Machado has nothing to disclose. Dr. Almeida has nothing to disclose. Dr. Matas has nothing to disclose. Dr. Bertolucci has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Janssen, Merck, Novartis, Roche, Servier. Dr. Naffah-Mazzacoratti has nothing to disclose.