Complementary and Alternative Medical Lab Testing Part 12: Neurology

By Ronald Steriti

Complementary and Alternative Medical Lab Testing (CAM Labs) contains summaries of the published research on lab tests, primarily from PubMed trials on humans. Each chapter (disease) begins with a brief summary of conventional lab tests, followed by additional lab tests, including diabetes, insulin resistance, metabolic syndrome, inflammation, etc. There are sections on endocrine hormones (thyroid, adrenal, sex steroids) and environmental medicine (toxic heavy metals). The nutritional assessments section includes minerals, vitamins and amino acids.

CAM Labs 12 - Neurology

1. Alzheimers Disease
2. Amyotrophic Lateral Sclerosis
3. Ataxia
4. Autism
5. Brain Injury
6. Cognitive Impairment
7. Epilepsy
8. Essential Tremor
9. Guillian-Barre Syndrome
10. Headache
11. Huntingtons chorea
12. Insomnia
13. Memory Loss
14. Migraine
15. Multiple Sclerosis
16. Muscular Dystrophy
17. Myasthenia Gravis
18. Narcolepsy
19. Parkinsons Disease
20. Peripheral Neuropathy
21. Sleep Apnea
22. Transverse Myelitis

• Language: English
• Publisher: Ronald Steriti
• Release date: May 29, 2016
• ISBN: 9781311934833

Ronald Steriti

Dr. Ronald Steriti is a graduate of Southwest College of Naturopathic Medicine and currently is researcher for Jonathan V. Wright at the Tahoma Clinic.

Book preview

Chapter 1. Alzheimers Disease

Alois Alzheimer, a German psychiatrist, first described Alzheimer’s disease in 1907. He noted the pathologic hallmarks of the disease, including neurofibrillary tangles and senile plaques. (Winslow et al., 2011)

Conventional Lab Tests

CBC, Thyroid panel (T3, T4, TSH) and Liver function tests

STD testing: VRDL for syphilis, HIV if young

Vitamin B12 and folate levels

Additional Lab Tests

Fasting Glucose, Hemoglobin A1C

Numerous studies have shown that people with type 2 diabetes have twice the incidence of sporadic AD. This relationship is so close that some authors have defined Alzheimer Disease as Type 3 Diabetes. (Vignini et al., 2013) (Kroner, 2009)

Type 2 diabetes mellitus (T2DM) causes brain insulin resistance, oxidative stress, and cognitive impairment, but its aggregate effects fall far short of mimicking AD. Extensive disturbances in brain insulin and insulin-like growth factor (IGF) signaling mechanisms represent early and progressive abnormalities and could account for the majority of molecular, biochemical, and histopathological lesions in AD. (de la Monte and Wands, 2008)

Insulin Resistance, Metabolic Syndrome

A study assessed the effect of metabolic syndrome on cognitive performance and decline over two years in 75 cases of early Alzheimer's disease (AD) and 73 healthy older adult controls in the Brain Aging Project. In healthy controls, a combined metabolic syndrome factor did not significantly predict cognitive performance, though higher insulin predicted poorer cognitive performance outcomes. In the AD group, higher scores on a combined metabolic syndrome factor predicted better cognitive outcomes. (Watts et al., 2013)

Altered metabolism, inflammation, and insulin resistance are key pathological features of both Alzheimer's disease (AD) and diabetes. (De Felice et al., 2014) (De Felice, 2013)

Hyperglycaemia induces increased peripheral utilization of insulin, resulting in reduced insulin transport into the brain. Defective insulin signalling make neurons energy deficient and vulnerable to oxidizing or other metabolic insults and impairs synaptic plasticity. (Bosco et al., 2011) (Wu et al., 2008)

C-Reactive Protein (CRP)

Low plasma levels of high-sensitivity C-reactive protein were associated with a significantly more rapid cognitive decline in a cohort of 122 patients having a clinical diagnosis of probable Alzheimer disease, each with at least 2 assessments across time. (Locascio et al., 2008)

Gamma-Glutamyl Transferase (GGT)

Gamma glutamyltransferase (GGT) plays a role in cellular glutathione uptake, which is an important element of antioxidant mechanisms. An increase in serum GGT is thought to be an early and sensitive marker of oxidative stress, which has a role in the pathogenesis of Alzheimer's disease. In this cross-sectional study, 132 patients with AD (mean age: 74.1 +/- 7.4, female 62.9%) and 158 age- and gender-matched normal controls (mean age: 74.5 +/- 6.3, female 67.1%) were evaluated. Median (min-max) GGT levels were 18 (9-70) in AD group and 17 (5-32) in normal controls. Mann-Whitney U test showed that GGT levels were significantly higher in AD patients (p = 0.012). Linear regression analysis revealed AD was an independent correlate of elevated GGT levels. GGT levels were increased significantly in AD patients. (Yavuz et al., 2008)

Comprehensive Thyroid Panel

TSH (Thyrotropin) in Women

The Framingham Study included 1864 cognitively intact, clinically euthyroid original cohort participants (mean age, 71 years; 59% women). During a mean follow-up of 12.7 years (range, 1-25 years), 209 participants (142 women) developed AD. Women in the lowest (<1.0 mIU/L) and highest (>2.1 mIU/L) tertiles of serum thyrotropin concentration were at increased risk for AD (multivariate-adjusted hazard ratio, 2.39 [95% confidence interval, 1.47-3.87] [P < .001] and 2.15 [95% confidence interval, 1.31-3.52] [P = .003], respectively) compared with those in the middle tertile. Thyrotropin levels were not related to AD risk in men. Analyses excluding individuals receiving thyroid supplementation did not significantly alter these relationships. In analyses limited to participants with serum thyrotropin levels of 0.1 to 10.0 mIU/L, the U-shaped relationship between thyrotropin level and AD risk was maintained in women but not when analyses were limited to those with thyrotropin levels of 0.5 to 5.0 mIU/L. Low and high thyrotropin levels were associated with an increased risk of incident AD in women but not in men. (Tan et al., 2008)

T4 (Thyroxine)

Thyrotropin, total and free thyroxine were examined in 665 men aged 71-93 years and dementia-free at baseline, including 143 men who participated in an autopsy sub-study. During a mean follow-up of 4.7 (S.D.: 1.8) years, 106 men developed dementia of whom 74 had AD. Higher total and free thyroxine levels were associated with an increased risk of dementia and AD (age and sex adjusted hazard ratio (95% confidence interval) per S.D. increase in free thyroxine: 1.21 (1.04; 1.40) and 1.31 (1.14; 1.51), respectively). In the autopsied sub-sample, higher total thyroxine was associated with higher number of neocortical neuritic plaques and neurofibrillary tangles. No associations were found for thyrotropin. These findings suggest that higher thyroxine levels are present with Alzheimer clinical disease and neuropathology. (de Jong et al., 2009)

T3 (Triiodothyronine)

A study compared 51 patients with Alzheimer’s disease, aged 55 years or older, with those of 49 healthy volunteers of similar age. The patients had significantly lower serum levels of T3 (P=0.03). Five patients and five controls had subclinical hypothyroidism (TSH>4.5). Moreover, six control subjects and none of the patients had subclinical hyperthyroidism (TSH<0.3). (Karimi et al., 2011)

Comprehensive Sex Steroid Panel

A literature review indicates that age-related losses of estrogens in women and testosterone in men are risk factors for AD. (Barron and Pike, 2012)

Estrogen

Overall, estradiol promotes the energetic capacity of brain mitochondria by maximizing aerobic glycolysis (oxidative phosphorylation coupled to pyruvate metabolism). The enhanced aerobic glycolysis in the aging brain would be predicted to prevent conversion of the brain to using alternative sources of fuel such as the ketone body pathway characteristic of Alzheimer's. (Brinton, 2008)

Estrogen in Women

The Leisure World Cohort includes 8,877 female residents of Leisure World Laguna Hills, a retirement community in southern California, who were first mailed a health survey in 1981. From the 2,529 female cohort members who died between 1981 and 1992, the authors identified 138 with Alzheimer's disease or other dementia diagnoses likely to represent Alzheimer's disease (senile dementia, dementia, or senility) mentioned on the death certificate. Four controls were individually matched by birth date (+/- 1 year) and death date (+1 year) to each case. The risk of Alzheimer's disease and related dementia was less in estrogen users relative to nonusers (odds ratio = 0.69, 95 percent confidence interval 0.46-1.03). The risk decreased significantly with increasing estrogen dose and with increasing duration of estrogen use. Risk was also associated with variables related to endogenous estrogen levels; it increased with increasing age at menarche and (although not statistically significant) decreased with increasing weight. This study suggests that the increased incidence of Alzheimer's disease in older women may be due to estrogen deficiency and that estrogen replacement therapy may be useful for preventing or delaying the onset of this dementia. (Paganini-Hill and Henderson, 1994) (Paganini-Hill and Henderson, 1996)

Testosterone in Men

A study included 28 older men with subjective memory loss or dementia. Serum total testosterone and sex hormone binding globulin (SHBG) correlated inversely with plasma levels of amyloid beta peptide 40 (Abeta40, r=-0.5, P=0.01 and r=-0.4, P=0.04, respectively). Calculated free testosterone was also inversely correlated (r=-0.4, P=0.03), and all three relationships remained statistically significant after allowing for age. A similar but non-significant trend was seen with dehydroepiandrosterone sulphate (DHEAS), and neither luteinising hormone (LH) nor estradiol correlated with Abeta40. These data demonstrate that lower androgen levels are associated with increased plasma Abeta40 in older men with memory loss or dementia, suggesting that subclinical androgen deficiency enhances the expression of Alzheimer's disease-related peptides in vivo. (Gillett et al., 2003)

A study included 83 referred Dementia of the Alzheimer's Type (DAT) cases and 103 cognitively screened volunteers (aged 75+/-9 years) from the Oxford Project To Investigate Memory and Ageing. Men with DAT (n=39) had lower levels (p =0.005) of total serum testosterone (TT=14+/-5 nmol/L) than controls (n=41, TT=18+/-6 nmol/L). Lower TT was more likely in men with DAT, independent of potential confounds (Odds Ratio=0.78, 95% C.I.=0.68 to 0.91). In women there was no difference in TT levels between cases (n=44) and controls (n=62). (Hogervorst et al., 2001)

DHEA

A nested case-control study examined baseline DHEA-S in participants of the Berlin Aging Study. Cases (n = 14) developed dementia of the Alzheimer type within 3 years. Control group A (n = 14) was matched for gender, age, multi-morbidity, and immobility. Control group B (n = 13) was matched for gender and age and comprised participants free from multi-morbidity, immobility, mult-medication, need of help, incontinence, visual impairment, hearing impairment, and depression. The mean plasma DHEA-S concentration of case subjects was 1.02 +/- 0.61 mumol/L. Both control groups had higher mean DEHA-S levels, in control group A, it was 1.89 +/- 1.24 mumol/L (p = .012) and in control group B 1.70 +/- 1.38 mumol/L (p = .093). (Hillen et al., 2000)

DHEA and Cortisol

Fourteen patients with AD and 12 healthy age-matched controls were studied. Mean cortisol levels were significantly increased and DHEAS titers were lowered in patients with AD, as compared with controls. Cortisol/DHEAS ratio was also significantly higher in patients. (Murialdo et al., 2000)

Fifty-two age-matched Alzheimer's disease (AD) patients (26 men, 26 women), mean age 76.2 years, were assessed. AD patients with higher levels of DHEAS scored better than those with lower levels on the subtests of Remembering a Name associated with a picture, Digit Span Total and Forward, and the Mini Mental Status Exam. AD patients with higher plasma cortisol levels performed worse on Delayed Route Recall than those with lower levels. (Carlson et al., 1999)

Melatonin

To determine whether melatonin production was affected in AD, melatonin levels were determined in the cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 1.1 yr) and in 82 age-matched controls (mean age, 76 1.4 yr). In AD patients the CSF melatonin levels were only one fifth (55 7 pg/mL) of those in control subjects (273 47 pg/mL; P = 0.0001). The melatonin level in AD patients expressing apolipoprotein E-epsilon3/4 (71 11 pg/mL) was significantly higher than that in patients expressing apolipoprotein E-epsilon4/4 (32 8 pg/ml; P = 0.02). (Liu et al., 1999)

Nutritional Assessments

Magnesium

One hundred and one elderly (>/=65 years) patients were consecutively recruited (mean age: 73.4+/-0.8 years; M/F: 42/59). AD patients had significantly lower MMSE scores (20.5+/-0.7 vs 27.9+/-0.2; p<0.001), and for the physical function tests. Mg-ion was significantly lower in the AD group as compared to age-matched control adults without AD (0.50+/-0.01 mmol/L vs 0.53+/-0.01 mmol/L; p<0.01). No significant differences were found in Mg-tot between the two groups (1.91+/-0.03 mEq/L vs 1.95+/-0.03 mEq/L; p=NS). For all subjects, Mg-ion levels were significantly and directly related only to cognitive function (Mg-ion/MMSE r=0.24 p<0.05), while no significant correlations were found in this group of patients between magnesium and ADL or IADL. (Barbagallo et al., 2011)

Thirty-seven patients (20 women, 17 men) and 34 controls were included in the study. There was a significant difference for Mg levels according to GDS (p = 0.030). Similarly, Mg levels were different between patients with low and high CDR stages (p = 0.003). Mg levels were lower in the group whose MMSE scores were <20 than in those whose MMSE scores were >/=20. A negative correlation was found between Mg levels and GDS and CDR (respectively: r = -0.35, p = 0.033; r = -0.360, p = 0.029). (Cilliler et al., 2007)

Zinc

43 patients with Alzheimer disease and 89 patients with normal cognitive function were evaluated. Mean zinc level from fingernail samples was 117.99 +/- 73.44 ppm in Alzheimer Disease patients, 123.86 +/- 77.98 ppm in control group (p: 0.680). (Kuyumcu et al., 2013)

To evaluate zinc status in Alzheimer's disease and Parkinson's disease, 29 patients with Alzheimer's disease, 30 patients with Parkinson's disease, and 29 age- and sex-matched controls were studied. Results showed a significantly lower blood zinc in patients with Alzheimer's and patients with Parkinson's than in controls. Urine zinc excretion, normalized to urine creatinine excretion, was not significantly different in either patient group compared to controls. These patients are probably zinc deficient because of nutritional inadequacy. (Brewer et al., 2010)

Homocysteine

In 32 healthy elderly individuals, homocysteine predicted follow-up cognitive scores and rate of decline in cognitive performance over a 5-year period. Homocysteine predicted word recall (p = 0.01), orientation (p = 0.02) and constructional praxis scores (p < 0.0001). One subject, with the second highest initial homocysteine, had developed probable AD at follow-up. (McCaddon et al., 2001)

In this pilot study, significantly elevated homocysteine levels were found in patients with Alzheimer's disease as well as in patients with vascular dementia, probably indicating similar pathophysiological pathways. (Leblhuber et al., 2000)

In a study at the author’s institute (Göteborg University, Mölndal, Sweden), however, they found serum-homocysteine (S-HCY) to be an early and sensitive marker for cognitive impairment. In patients with dysmentia (mild cognitive impairment), no less than 39% had pathological S-HCY levels, indicating insufficient 1-carbon metabolism. (Gottfries et al., 1998)

Thirty patients, aged 65 or over, seen consecutively in 1994 with features compatible with DSM-III-R criteria for primary degenerative dementia of Alzheimer type and 30 cognitively intact age-matched control subjects. Patients had a highly significant elevation of tHcy compared with control (p < 0.0001). Multiple regression highlighted the interrelated effects of tHcy and total serum cobalamin on cognitive scores. (McCaddon et al., 1998) (Lehmann et al., 1999)

Vitamin B12

The study took place at a memory-clinic of a department of geriatric medicine in a teaching hospital. There were seventy-three consecutive outpatients with probable AD, including 61 patients with normal and 12 patients with subnormal (<200 pg/ml) vitamin B12. Controlling for dementia duration and degree of severity of the cognitive deficits, there were significant inverse associations between vitamin B12 status and ICD-10 irritability (p=0.045) and NOSGER subscale disturbed behaviour (p=0.015). Low vitamin B12 serum levels are associated with BPSD in AD. (Meins et al., 2000)

The patients were 97 consecutive referrals to an AD clinic. Forty patients had either possible or probable AD, 31 had other dementias (OD) and 26 had mild cognitive impairment (cognitively impaired, not demented; CIND). In the AD group, only B12 was significantly correlated with MMSE. Using regression analysis, B12 contributed significantly to variance in MMSE. (Levitt and Karlinsky, 1992)

Vitamin B12 and Folate

A population-based longitudinal study in Sweden, the Kungsholmen Project: A random sample of 370 non-demented persons, aged 75 years and older and not treated with B(12) and folate, was followed for 3 years to detect incident AD cases. When using B(12) < or =150 pmol/L and folate < or =10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B(12) or folate had twice higher risks of developing AD (RR = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B(12) or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B(12)

Homocysteine, Vitamin B12 and Folate

Twenty-two VaD patients, 22 AD patients and 24 healthy subjects were studied. Folates were significantly reduced in both VaD (10.8 +/- 2.81 nmol/l) and AD (10.0 +/- 2.72 nmol/l; p<0.001) patients, while vitamin B12 showed significantly reduced levels only in AD patients (392.1 +/- 65.32 pmol/l; p=0.02). Increased levels of Hcy associated with low vitamin B12 plasma levels were found only in AD patients. (Malaguarnera et al., 2004)

Case-control study of 164 patients, aged 55 years or older, with a clinical diagnosis of dementia of Alzheimer type (DAT), including 76 patients with histologically confirmed AD and 108 control subjects. Serum tHcy levels were significantly higher and serum folate and vitamin B12 levels were lower in patients with DAT and patients with histologically confirmed AD than in controls. The odds ratio of confirmed AD associated with a tHcy level in the top third > or = 14 micromol/L) compared with the bottom third < or = 11 micromol/L) of the control distribution was 4.5 (95% confidence interval, 2.2-9.2). (Clarke et al., 1998)

Vitamin B6 (PLP, P5P)

Low vitamin B6 levels are associated with white matter lesions in Alzheimer's disease. (Mulder et al., 2005)

Forty-three patients with AD and 37 control subjects without AD were studied. The OR for low plasma PLP (<25 nmol/L) was 12.3 (p = 0.01) for patients with AD. (Miller et al., 2002)

Vitamin B1

A study compared the intake and functional levels of vitamins B6, C and B1 in 15 pairs of Alzheimer's disease and normal subjects. These were similar in both groups, except that B1 had lower functional values for the subjects with Alzheimer's disease. (Agbayewa et al., 1992)

Vitamin C

Patients with dementia who fulfilled criteria for Alzheimer's disease: severe Alzheimer group (N = 20), Mini-Mental State Examination (MMSE) score range 0-9; moderate Alzheimer group (N = 24), MMSE 10-23; hospitalized Alzheimer group (N = 9), MMSE 10-23. Control group (N = 19), MMSE 24-30. In the home-living Alzheimer subjects, vitamin C plasma levels decreased in proportion to the severity of the cognitive impairment despite similar vitamin C intakes. Plasma vitamin C is lower in AD in proportion to the degree of cognitive impairment and is not explained by lower vitamin C intake. (Riviere et al., 1998)

Vitamin E

A study compared CSF and serum levels, and the CST/serum ratio of alpha-tocopherol (vitamin E) in 44 apparently well-nourished patients with Alzheimer's disease (AD) and 37 matched controls. CSF and serum vitamin E levels were correlated, both in AD patients and in controls. The mean CSF and serum vitamin E levels were significantly lower in AD patients. (Jimenez-Jimenez et al., 1997)

Beta-Carotene and Vitamin A

In 38 AD patients and 42 controls, the serum levels of beta-carotene and vitamin A were significantly lower in the AD-patient group. (Jimenez-Jimenez et al., 1999)

Neopterin

Plasma samples from patients with mild-to-moderate AD (N = 34), aMCI (N = 27), and cognitively normal controls (N = 30) were obtained from the Johns Hopkins Alzheimer's Disease Research Center. AD subjects had significantly higher neopterin values compared with aMCI (beta = 0.202, p = 0.004) and normal (beta = 0.263, p = 0.0004) subjects. There was no statistically significant difference between normal and aMCI subjects. Significant associations between neopterin and IFN-gamma (r = 0.41, p < 0.0001) and IL-6 (r = 0.35, p = 0.0006) levels were found. (Parker et al., 2013)

Forty-three probable AD patients were investigated at baseline and follow up (14.5+/-0.5 months; mean+/-s.e.m.). The mean neopterin concentrations increased significantly from 9.8+/-1.0 to 13.6+/-2.1 nM (p=0.04). At follow up, the increase of neopterin correlated significantly with the decrease in the total CERAD and MMSE scores, according to the clinical progression (r=-0.353, p<0.05 and r=-0.401, p<0.01, respectively). (Blasko et al., 2007)

Plasma neopterin levels were higher in 51 patients with AD (9.3 +/- 5.9 ng/mL) than in 38 age-matched control subjects (6.3 +/- 2.6 ng/ml, p = 0.002). (Hull et al., 2000)

A study compared 24 patients with Alzheimer's disease (8 males, 16 females; age: 73.1+/-6.2 years; free of any infectious process) and fourteen controls of similar age (4 males, 10 females; age: 69.7+/-8.8 years). Compared to controls, significantly higher concentrations of neopterin (p< 0.01) were found in patients with Alzheimer's disease. Among patients, concentrations of neopterin were higher in those with lower mini-mental-state (p < 0.05), and an inverse correlation existed between mini-mental-state and neopterin concentrations. (Leblhuber et al., 1999)

Significantly lower mean plasma total biopterin in 18 patients with senile dementia of Alzheimer type. (Smith, 1984)

Docosahexaenoic Acid (DHA)

Low serum docosahexaenoic acid is a significant risk factor for Alzheimer's dementia. (Kyle et al., 1999)

Heavy Metals

Aluminum

A study investigated a possible relation between aluminum concentration (Al) in public drinking water and Alzheimer's disease (AD). Using the case/control odds ratio as an estimate of relative risk and aluminum > or = 100 microgram/L as the cutoff point, elevated risks for histopathologically verified AD were associated with higher aluminum. Comparing all AD cases with all non-AD controls, and using the aluminum of public drinking water at last residence before death as the measure of exposure, the estimated relative risk associated with aluminum > or = 100 microgram/L was 1.7 (95% CI: 1.2-2.5). Estimating aluminum exposure from a 10-year weighted residential history resulted in estimates of relative risk of 2.5 or greater. (McLachlan et al., 1996)

Mercury

A study measured blood mercury concentrations in AD patients (n = 33), and compared them to age-matched control patients with major depression (MD) (n = 45), as well as to an additional control group of patients with various non-psychiatric disorders (n = 65). Blood mercury levels were more than two-fold higher in AD patients as compared to both control groups (p = 0.0005, and p = 0.0000, respectively). In early onset AD patients (n = 13), blood mercury levels were almost three-fold higher as compared to controls (p = 0.0002, and p = 0.0000, respectively). These increases were unrelated to the patients' dental status. Linear regression analysis of blood mercury concentrations and CSF levels of amyloid beta-peptide (A beta) revealed a significant correlation of these measures in AD patients (n = 15, r = 0.7440, p = 0.0015, Pearson type of correlation). (Hock et al., 1998)

Mercury and Manganese

Comparison was made with between 173 patients with AD and in 87 patients with the combination of AD and minor vascular components (AD + vasc) and 54 healthy controls. The plasma concentrations of manganese and total mercury were significantly higher in subjects with AD (p < 0.001) and AD + vasc (p

Iron

Thirty-one AD and sixty-eight healthy control subjects participated in this study. High- and low-field strength MRI instruments were used in combination to quantify iron content of ferritin molecules (ferritin iron) using the field dependent relaxation rate increase (FDRI) method. Decreased transverse relaxation rate (R2) was used as an index of tissue damage. Compared with healthy controls, AD subjects had increased ferritin iron in hippocampus (p = 0.019) but not thalamus (p = 0.637), and significantly decreased R2 in hippocampus (p < 0.001) but not thalamus (p = 0.37). In the entire sample, FDRI and R2 were negatively correlated. The data shows that in AD, hippocampus damage occurs in conjunction with ferritin iron accumulation. (Raven et al., 2013)

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