Dementia: Test and Diagnosis

1st order laboratory parameters – obligatory laboratory tests.

Small blood count [MCV ↑ → possible indication of alcohol dependence, vitamin B12 and folic acid deficiency]
Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
Electrolytes – sodium, potassium, calcium.
Fasting glucose (fasting plasma glucose; preprandial plasma glucose; venous), oral glucose tolerance test (oGTT) if necessary.
Liver parameters – aspartate aminotransferase (AST, GOT), alanine aminotransferase (ALT, GPT), gamma-glutamyl transferase (γ-GT, gamma-GT; GGT) [γ-GT ↑, possible indication of alcohol dependence].
Renal parameters – urea, creatinine, possibly cystatin C or creatinine clearance.
TSH (thyroid-stimulating hormone) – to exclude hypo- or hyperthyroidism (hypothyroidism or hyperthyroidism).
Vitamin B12 (recommendation grade B)
CSF diagnostics – initial diagnosis when there is evidence of inflammatory brain disease.

Laboratory parameters 2nd order – depending on the results of the history, physical examination, etc. – for differential diagnostic clarification.

Apolipoprotein E genotype 4 (ApoE4 ) as a genetic marker (risk factor for the occurrence of dementia; indication: prescient senile dementia in the circa 6th decade of life without evidence of genetic burden from parents, grandparents)Note: An isolated determination of the apolipoprotein E genotype is not recommended (recommendation grade A).
- Prospective studies show that high serum cholesterol levels (hypercholesterolemia) in middle age and apoE4 together increase the risk of AD.
- Numerous epidemiological studies show that atherosclerosis-related risk factors (arteriosclerosis, hardening of the arteries), which are also vascular risk factors, are crucial in middle age for the development of later Alzheimer’s dementia.
Evidence of Alzheimer’s disease pathology by at least one of the following criteria:
- Positive amyloid detection with positron emission tomography (PET).
- Genetic test (DNA analysis): mutation leading to monogenically mediated Alzheimer’s disease (mutation on the genes presenilin 1 or presenilin 2 or on the gene of the amyloid precursor protein, APP) [see below Alzheimer’s disease/causes].
- CSF diagnostics (recognized dementia biomarkers are amlyoid-β1-42 (Aβ1-42), amlyoid-β1-40 (Aβ1-40), total tau and phospho-tau-181 (pTau), and 14-3-3 protein) [decreased Aß42 in CSF and increased tau protein or phosphorylated tau protein in CSF]In addition, CSF diagnostics (see below) exclude inflammatory CNS diseases.
Tau proteins (determination by “single molecule array”; detection limit of tau proteins was lowered to 0.019 pg/ml) – detection of impending dementia and related disorders already 4 years before the first symptoms.
Differential blood count
Blood gases (ABG), arterial
Drug screening including narcotics (alcohol, barbiturates, benzodiazepines, bromides).
Lues serology: VDRL test (for V. d. on neurolues).
HIV serology
Borrelia serology
Phosphate
HbA1c
Homocysteine
Advanced thyroid diagnostics – fT 3, fT4, SD antibodies.
Cortisol
Parathyroid hormone – to exclude hypo- or hyperparathyroidism (parathyroid hypo- or hyperfunction).
Coeruloplasmin – if Wilson’s disease is suspected.
Serum albumin
Ammonia level
Folic acid, vitamin B1, B6
Copper
Heavy metals (arsenic, lead, mercury, thallium).
CO hemoglobin
Carbodeficient transferrin (CDT) ↑ (in chronic alcoholism)* .
CSF diagnostics – to exclude infectious and autoimmunological diseases (e.g., sarcoidosis, vasculitis, autoimmune encephalitides).

* With abstinence, the values normalize within 10-14 days.

Apolipoprotein E genotyping

Apo E	Allele combination	Frequency	Clinical effects
Genotype E2	E2/E2	approx. 0.5	Association with type III of Fredrickson’s hyperlipoproteinemia (familial dysbetalipoproteinemia; incidence approximately 1:2,000). Lowered risk for LDL cholesterol elevation. Heterozygous or homozygous ApoE2 carriers with combinations 2/3 and 2/2 (together about 5% of the population) have about 40.0% lower risk of dementia.
Genotype E2	E2/E3	ca 10.0 %	Decreased risk of LDL cholesterol elevation. Heterozygous or homozygous ApoE2 carriers with combinations 2/3 and 2/2 (approximately 11.0% of the population) have an approximately 40.0% lower risk of disease for dementia.
Genotype E3	E3/E3	approx. 60.0 %	Intermediate risk for LDL cholesterol elevation.
Genotype E4	E2/E4	approx. 2.5	Predisposed to the familial late form as well as the sporadic form of Alzheimer’s-type dementia; have an approximately 2.6 increased lifetime risk (European/Caucasian)
	E3/E4	approx. 24.0	Risk for LDL cholesterol elevation Predisposition to familial late-onset form as well as sporadic form of Alzheimer’s-type dementia; have approximately 3-fold increased lifetime risk compared to 3/3 carriers (approximately 60% of population)
	E4/E4	approx. 3 %	Risk for LDL cholesterol elevation Predisposition to familial late-onset form as well as sporadic form of Alzheimer’s-type dementia; have up to 10-fold increased risk of developing Alzheimer’s dementia.

Of those with AD, approximately 45% are heterozygous and 10-12% are homozygous carriers of the epsilon 4 alleleAn isolated determination of the apolipoprotein E genotype as a genetic risk factor is not recommended due to lack of diagnostic discriminatory power and predictive value in the diagnostic setting.