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Novel Biomarkers and Therapeutic Options to Address Neuronal Injury
Table 1: Efficacy Studies of High-dose Vitamin B Therapy in Cognitive Impairment
Study Design and Objective
(Author, Year) Patient Population Results Conclusion
Double-blind, placebo-controlled study with 818 participants aged 50–70 years from Improvements in global cognitive function Folate therapy improved functions that
random assignment of 800mcg folic acid the FACIT trial with Hcy levels >13µmol/l. (p=0.033), memory (p=0.010), and tend to decline with age.
supplementation; three-year follow-up to Baseline MMSE = 29. All participants information processing speed (p=0.016).
compare cognitive performance. (Durga, 2007
48
) were B
12
-replete. No effect on complex speed and word fluency.
Double-blind, placebo-controlled pilot study to 57 consecutive outpatients with AD. The improvement in IADL scores and the The effect of folate supplementation on
assess random assignment for six months of Mean age 76.27±6.23 years. Baseline combined IADL/SB scores was statistically ChI was positive on secondary outcome
1mg of folic acid supplementation and ChI, and MMSE = 23.49±3.53. significant (both p=0.03) and not related to measures and improvement suggests
whether outcome measures were affected by changes in Hcy; no change in MMSE scores. that folate may act synergistically with ChI.
changes in Hcy levels. (Connelly, 2007
49
)
Prospective, observational study to examine 579 non-demented participants (age 49–93 57 participants developed AD after a mean After adjusting for age, gender, education,
whether diet plus intake of vitamins is years) from the Baltimore Longitudinal Study of follow-up of 9.3 years. Cox regression analysis and caloric intake, folate was associated
associated with a reduced risk for AD. Aging. Age at first intake report: 69.6 years of all variables found that only total intake of with a reduced risk (RR=0.45) for AD.
(Corrada, 2005
50
) (range 49–93); age at last follow-up: 78.9 years folate (diet plus vitamins) at or above the
(range 61–102). RDA was significant for reduced risk of AD.
Double-blind, placebo-controlled study to 211 women without dementia in three age Supplements had a significant positive effect Folate intake was associated with
assess the effects on cognition and mood groups: 25.20±3.19 years (n=56), on various standardized tests of cognitive improved performance on a variety of
from random assignment of 750mcg 49.19±2.6 years (n=80), 74.08±5.75 years processing resources, memory, executive measures of cognition (speed, memory,
folic acid, 15mcg B
12
, 75mg B
6
, or (n=75). function, and verbal ability, but no effect on and fluency); vitamin B
12
and vitamin
placebo for 35 days. (Bryan, 2002
51
) self-reported mood measures. B
6
intake was associated with improved
memory performance.
Patients in the treatment arm received an oral The treatment arm consisted of 30 consecutive Hcy levels returned to normal values of 9.5µmol/l No MCI patient progressed to dementia.
prescription of 10mg folic acid, 2mg B
12
, and ambulatory patients with mild cognitive (p<0.0001); albumin ratio decreased from Treatment with a high-dose combination
80mg B
6
for an average of 270 days. impairment, elevated serum Hcy levels, and baseline, indicating an improvement in blood– of vitamin B
12
–B
6
–folate appears to
(Lehmann, 2003
52
) a mean age of 72 years; the control arm brain barrier function (p<0.0002); MMSE improve blood–brain barrier function
consisted of 35 healthy age-matched controls scores remained unchanged; CSF-tau was in patients with mild cognitive impairment
with a mean age of 68 years. expected to increase, but an unexpected and hyperhomocysteinemia.
downward trend was observed.
Open-label trial to determine the effect of 33 consecutive patients with mild to Following vitamin therapy, Hcy levels were An elevated plasma Hcy concentration
two months’ supplementation with 5mg moderate dementia. Mean age 78.4±8.1 reduced to 11µmol/l (p <0.001) and MMSE is a valuable marker for detecting
folic acid and 1mg cyanocobalamin for years and plasma Hcy levels >19.9µmol/l. and SKT scores were significantly improved psychogeriatric patients with treatable
two months on cognitive function in (p<0.01). cobalamin/folate deficiency.
elderly patients with dementia. (Nilsson, 2001
53
)
Ad hoc, double-blind, placebo-controlled 30 volunteers (mean age 80.23±5.53 years) Greater folate deficiency at the beginning Patients treated with folate showed a
pilot study in which patients were randomly with serum folate levels <3ng/ml. Very mild of treatment was related to greater cognitive significant improvement in both memory
assigned 15mg folic acid or placebo to moderate cognitive decline as assessed improvement over two months of treatment and attention efficiency. Degree of
for 60 days. (Fioravanti, 1997
54
) by GDS. MMSE scores 16–24. as measured by RMT. memory improvement was positively
correlated with initial severity of folate
deficiency. Severity of initial cognitive
decline was unrelated to the degree
of folate deficiency.
Open-label trial using folinic acid 38 patients with conditions that included Patients treated with folinic acid experienced A relationship was observed between
supplementation to study the relationship depression, asthenia, irritability, forgetfulness, an increase in folate levels (192 versus 347ng/ml) folate deficiency and decreases in learning,
between folate deficiencies and lack of attention, and erythrocyte folate levels and improvements in Zung depression and memory, concentration, and vigilance;
neuropsychiatric disturbances. <300ng/ml were matched with 100 BRC scores. deterioration of associative memory and
(Rapin, 1988
55
) age-matched controls (62±5 years). disruption of spatio-temporal organization
had the greatest association with folate
deficiency. After treatment patients reported
that they ‘feel better’ and ‘have more
interest in life.’
Open-label trial to determine the effect of 50 patients (age 81±7 years) were enrolled Depression symptoms were resolved in
50mg folinic acid given parenterally (on from a frequency study in which 75% of four patients; self-sufficiency was recovered in
days one, 11, and 21) to patients with folate 1,000 elderly hospitalized patients were three dementia patients; and 32 patients
deficiency and depression and/or dementia. folate-deficient (serum folate <5ng/ml). showed improvement in either geriatric or
(Brocker, 1986
56
) psychiatric scores.
AD = Alzheimer’s disease; FACIT = folic acid and carotid intima-media thickness; ChI = cholinesterase inhibitor; MMSE = Mini-Mental State Examination; MCI = minimal cognitive impairment;
IADL = instrumental activities of daily living; SKT = Syndrom-Kurztest short cognitive performance test; SB = social behavior subscale; RDA = recommended daily allowance; GDS = global
deterioration scale; RMT = Randt memory test; BRC = a battery of rating scales.
US NEUROLOGY 29
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