Dementia, Alzheimer’s-type

Medicinal chemistry has many examples of the development of successful therapeutics based on an exploration of endogenous compounds. The treatment of diabetes mellitus, for example, is based upon the administration of insulin, the hormone that is functionally deficient in this disease. The current treatment of Parkinson s disease is based upon the observation that the symptoms of Parkinson s disease arise from a deficiency of dopamine, an endogenous molecule within the human brain. Since dopamine cannot be given as a drug since it fails to cross the blood-brain barrier and enter the brain, its biosynthetic precursor, L-DOPA, has been successfully developed as an anti-Parkinson s drug. Analogously, the symptoms of Alzheimer s disease arise from a relative deficiency of acetylcholine within the brain. Current therapies for Alzheimer s-type dementia are based upon the administration of cholinesterase... 

The Rb-82 generator permits serial studies in the same patient as often as every 10 minutes with 20-60 mCi of Rb-82 for rapid bolus intravenous infusion. Inherent in the administration of high levels of Rb-82 activity is the need for precise flow control from an automated system to deliver the desired amount of radioactivity. The development of the alumina column parameters and the elution protocol as well as the automated microprocessor system controller are presented here. Some of the details of this system have been discussed in earlier publications (15,21). Generator produced Rb-82 is used as a diffusible flow tracer in myocardial perfusion studies and as a nondiffusible tracer in brain studies to assess blood brain barrier permeability changes in patients with brain tumors or Alzheimer s type dementia. 

What are the Alzheimer s type dementia clinical signs and symptoms ... 

There is no blood test or X-ray to diagnose Alzheimer s-type dementia per se, but there are tests for causes of dementia syndromes that may at first look like Alzheimer s disease, and often those causes are treatable. 

Another example is the patient who has Alzheimer s-type dementia. The preferred available antidepressant medications for patients who have both Alzheimer s disease and depression include the SSRIs and venlafaxine because they have the lowest probability of adverse cognitive side effects. Patients with Alzheimer s disease should generally avoid TCAs (they are too anticholinergic, and they worsen cognitive function, in addition to all of the other TCA side effects) they should avoid bupropion (increased confusion) and fluoxetine (too agitating for seniors generally, especially those with Alzheimer s disease). 

The term therapeutic touch is used to mean a particular hands-on therapy, as well as the entire realm of hands-on techniques, such as Reiki, Touch for Health, Jin Shin Jyutsu, and some forms of Reconnective Healing. In addition to reducing stress and anxiety, therapeutic touch has been shown to have positive effects on many conditions linked to acidity in the body, including osteoarthritis, cancer, irritable bowel syndrome, and Alzheimer s-type dementia.10 It can provide an increased sense of comfort and well-being, reduce pain, and in some cases improve symptoms and the condition itself. More study is required to validate the power of therapeutic touch as a treatment, either stand-alone or in combination with other healing therapies and medical treatments. But because therapeutic touch has no side effects and can help reduce stress, it is a welcome addition to the Kick Acid program, should you choose to incorporate it. 

Chan-Palay, V., Lang, W., Allen, Y.S., Haesler, U. Polak, J.M. (1985b) II Cortical neurons immunoreactive with antisera against neuropeptide Y are altered in Alzheimer s-type dementia. J. Comp. Neurol. 238, 390-400. 

Tomiyama, T., Nagata, T., Shimada, H., et al., 2008. A new amyloid beta variant favoring oligomerization in Alzheimer s-type dementia. Ann. Neurol. 63, 377-387. 

Other nootropic agents in some stage of clinical development include nebracetam (9), nefinacetam (10), and BMY 21502 (11). Nebracetam, an aminomethyl pyrrolidinone derivative, is expected to be approved in Japan in 1994 (73). In clinical studies involving patients having cerebrovascular or senile dementia of the Alzheimer s type, clinical symptoms such as spontaneous or emotional expression were enhanced in up to 71% of cases. Long-term treatment using nebracetam in patients with cerebral infarction also afforded marked improvement in most cases with few side effects (74). A review of this compound has beenpubUshed (75). 

AD is the most common type of dementia, affecting approximately 4.5 million Americans in the year 2000.2 Table 32-2 lists the different classifications of dementia.3 This chapter will address only dementia of the Alzheimer s type. 

Dementia of the Alzheimer s type (early- or late-onset)... 

The ChE inhibitors all have the indication for the treatment of mild to moderate dementia of the Alzheimer s type. Guidelines for the treatment of AD were written before the approval of memantine and recommend the use of ChE inhibitors as a valuable treatment for AD.27-29 None of the ChE inhibitors have been compared in head-to-head studies, so the decision to use one over another is based on differences in mechanisms of action, adverse reactions, and titration schedules. 

Donepezil is approved for the treatment of mild to moderate dementia of the Alzheimer s type at a dose of 5 mg/day. This dose should be increased to 10 mg/day if needed after 4 to 6 weeks. Table 32-5 describes the dosing strategies for all of the approved agents for Alzheimer s disease.34-38... 

The first neurochemical evidence of a disturbed serotonin function in cognition came from the changes in serotonin and/or 5-hydroxyindoleacetic acid (5-HIAA) levels in a number of forebrain nuclei, the temporal and cingulate cortex, hippocampus, and other areas of the brain taken at autopsy from patients with senile dementia of the Alzheimer s type (Adolfsson et al. 1978 Arai et al. 1984 D. M. Bowen et al. 1979, 1983 A. J. Cross et al. 1983 Winblad et al. 1982). The depletions are regionally selective reductions in se-... 

Similar results were obtained from material taken from patients with senile dementia of the Alzheimer s type (Chan-Palay et al. 1992). A loss of tryptophan hydroxylase immunoreactive neurons in the raphe nuclei, which was most pronounced in the lateral division, was correlated with both age and cortical pathology. Furthermore, tyrosine hydroxylase reactive neurons were also found to be reduced in the locus coeruleus, even more so than the tryptophan hydroxylase reactive neurons. The same was also found for material taken from brains with Parkinson s disease. 

Hong J-S, Tilson HA, Yoshikawa K Effects of lithium and haloperidol administration on the rat brain levels of Substance P. J Pharmacol Exp Ther 224 590-597, 1983 Honig A, Bartlett JR, Bouras N, et al Amino acid levels in depression a preliminary investigation. J Psychiatr Res 22 159-164, 1989 Honjo H, Ogino Y, Natitoh K, et al In vivo effects by estrone sulphate on the central nervous system on senile dementia [Alzheimer s type). Journal of Steroid Biochemistry 34 521-525, 1989... 

Nemeroff CB, Krishnan KRR, Reed D, et al Adrenal gland enlargement in major depression a computed tomographic study. Arch Gen Psychiatry 49 384-387, 1992 Nestler EJ, Terwilliger RZ, Duman RS Chronic antidepressant administration alters the subcellular distribution of cyclic AMP-dependent protein kinase in rat frontal cortex. J Neurochem 53 1644-1647, 1989 Nestor PC, Parasuraman R, Haxby JV, et al Divided attention and metabolic brain dysfunction in mild dementia of the Alzheimer s type. Neuropsychologia 29(5) 379-387, 1991... 

Prince DA, Wilder BJ Cortical mechanisms in cortical epileptogenic foci surrounded inhibition. Arch Neurol 16 194-202, 1967 Prinz PN, Vitahano PP, Vitiello MV, et al Sleep, EEC and mental function changes in senile dementia of the Alzheimer s type. Neurobiol Aging 3 361-370, 1982... 

Memantine is currently the only medication approved by the FDA for the treatment of moderate to severe dementia of the Alzheimer s type (Reisberg et al. 2003 Winblad and Poritis 1999). Although its use also has been investigated in patients with mild to moderate vascular dementia (Orgogozo et al. 2002 Wilcock et al. 2002), this specific use has not yet been approved. 

Persistent excitatory glutamatergic stimulation of postsynaptic NMDA receptors, which may cause neuronal toxicity by allowing excessive calcium entry into neurons, has been implicated in the symptomatology of dementia of the Alzheimer s type (Farber et al. 1998). Memantine is a moderate-affinity, noncompetitive inhibitor of NMDA receptors (Danysz et al. 2000). 

Chatellier G, Lacomblez L Tacrine (tetrahydroaminoacridine THA) and lecithin in senile dementia of the Alzheimer s type a multicentre trial. Groupe Fran(jais d Etude de la Tetrahydroaminoacridine. BMJ 300 495-499, 1990... 

Brain Studies. Rubidium-82 has also been used to study blood brain barrier changes in patients with brain tumors or Alzheimer s type senile dementia (28-30). The method of study is similar to the heart studies without gating. Figure 11 shows the uptake of Rb-82 in the three levels of a brain tumor. This non-invasive procedure provides information on the size and vascularity of the tumor. In the slice OM + 10 there is a vascular rim and a necrotic center in the tumor. The metabolism of glucose was determined in the same tumor patient using F-fluorodeoxyglucose produced on a cyclotron and the results correlated well with Rb-82 distribution. 

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