The Role of Supplemental Antioxidants in Preventing Memory ... · The Role of Supplemental...
Transcript of The Role of Supplemental Antioxidants in Preventing Memory ... · The Role of Supplemental...
> 9,000 patients
4 full-time GP’s
≈ 10 new dementia cases pa
40+ established dementia
Homocysteine - mechanisms
Why IS homocysteine raised?
Case Studies
CBS
Cysteine
Cystathionine
Serine
Transsulfuration Pathway
THF
Methyl-THF
Methylene-THF
Serine
Glycine Methionine
SAM
SAH
Homocysteine
MS B12
Acceptor
Methylated Acceptor
ATP
Methionine Cycle
Folate Cycle
MTHFR
Glutathione
Dietary protein
McCaddon et al Biological Psychiatry 2003 (53): 254-260 Box & Whisker Plot: CYSTEINE
Mean ±SE ±1.96*SE ALZ CON
DIAG
105
110
115
120
125
130
135
140
145CY
STEI
NE
(50 AD patients v 57 controls)
Cysteine
CBS
Cysteine
Cystathionine
Serine
Transsulfuration Pathway
THF
Methyl-THF
Methylene-THF
Serine
Glycine Methionine
SAM
SAH
Homocysteine
MS B12
Acceptor
Methylated Acceptor
ATP
Methionine Cycle
Folate
Cycle
MTHFR
Glutathione
Could ↑Hcy reflect oxidative stress?
Glutathione McCaddon et al Biological Psychiatry 2003 (53): 254-260
Limited pathways to remove homocysteine in the brain The major pathway is impaired by oxidative stress
Inflammation Oxidative Stress
Why NAC?...
Safe, and orally bioavailable
Antioxidant in and of itself (via SH group)
Cysteine precursor Increased GSH
Lowers Hcy Urinary excretion
Oral NAC (600 mg daily) added. 1/12 later “..livelier and happier” MMSE improved to 25/30; regained ability to recall 3 objects
Mild cognitive deficits (27/30 on MMSE) Diagnosis? ‘Age-associated memory impairment’
70 yr old lady 1 yr H/O ST memory loss Controlled hypothyroidism
MMSE fell to 22/30. Borderline low B12 (195 ng/L) and folate (4.6 µg/L) Elevated tHcy (16.5 µmol/L) Low glutathione (2.1 µmol/l)
Commenced monthly im OH-B12 (1 mg) and oral folic acid (5 mg)
BUT cognitive function unchanged over 6/12 (21/30 on MMSE)
Memory declined over next 3 yrs - Forgot to convey messages to husband Inappropriate questions - enquired after deceased friends
Continued on this Tx for last 3 years; scored 27/30 on most recent MMSE
Now on AchE inhibitor in addition to B vitamins and NAC
71 yr old retired telecom engineer 10 yr H/O gradual ST memory impairment Frequently mislaid objects / forgot people’s names Father † senile dementia aged 74
Poor 6CIT (12/28). Elevated tHcy (15.6 µmol/L) but normal B12 (368 ng/L),
folate (9.3µg/L) and RCF (492 µg/L)
Diagnosis? Probable SDAT
Commenced oral CN-B12 (1mg) folate (5mg) and NAC (600mg)
Wife reported a “.. definite and immediate improvement” within 2 weeks
tHcy fell to 9.6 µmol/L. 1/12 later scored 28/30 on MMSE
Summary Homocysteine is a modifiable risk factor for cognitive impairment and cognitive decline
Homocysteine is likely also a marker of neuro-inflammatory oxidative stress in these patients
NAC can be used together with B-vitamins to address oxidative stress and lower blood Hcy
Can we delay the onset of dementia?