Abstract
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.
Disputes & Debates: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.