Dementia subtypes

Clinical observations and case reports suggest that fluctuating levels of consciousness (FC) occur in 80-90% of patients with DLB (Byrne et al., 1989 McKeith et al., 1992). In addition, FC occur in 20-25% of patients with AD (Kolbeinsson and Jonsson, 1993 Robertson et al., 1998) and between 35-50% of VaD (Hachinski et al., 1975 Roman et al., 1993) although the periodicity and causality in these dementia subtypes is hypothesized to be different (Walker et al., 2000a). These fluctuations in consciousness are characterized by periodic shifts in the level of arousal ranging from episodes of lucidity to reduced awareness and even stupor. 

Dementia is characterised by a progressive decline in cognitive function. The prevalence of dementia increases with age. With the demographical changes, the number of patients with dementia will increase. There are three major forms of dementia Alzheimer s disease, vascular dementia and a mixed dementia. Beside these, there are several less common subtypes of dementia. 

Tacrine is not an ester and interferes only with the choline-binding site of AChE. It is effective in alleviating symptoms of dementia in some subtypes of Alzheimer s disease. 

Metabotropic glutamate receptors act via G proteins and a variety of different types have been resolved. Class I (subtypes 1 and 5), Class II (subtypes 2 and 3), Class III (subtypes 4, 6, 7 and 8) and phospholipase D (PLD)-coupled mGlu-Rs couple through G proteins to increase PLC via Gao/Gaq (Class I), decrease adenylyl cyclase via Gai (Classes II and III) and to increase PLD-coupled mGlu-R. The glutamate receptors are excitatory and agonists can be neurotoxic. such as Amanita-derived ibotenic acid and the Guam cycad amino acid BMAA ((3-jV-methylamino-i-alanine), which causes a type of dementia (Table 5.5). 

Dementia occurring as a result of stroke is a subtype of vascular dementia. 

Late-onset Alzheimer s disease (AD) is the most prevalent subtype of age-related dementia accounting for 60% of cases of dementia and with a mean prevalence estimate of 3.4% (Kalaria et al., 2008). If growth in the older population continues, it is projected that the prevalence of AD will nearly quadruple in the next 50 years, by which time approximately 1 in 45 individuals will be afflicted with the disease (Brookmeyer et al., 1998). 

The sCJDW2 subtype has a W at PrP codon 129 and type 2 PrP It is the second most common form of sCJD and accounts for 16% of all sporadic human prion disease. The mean age at onset is 60 years and the mean duration of the clinical phase is six months. Ataxia is the most common presenting symptom for this subtype. At later stages, dementia almost always develops and is accompanied by myoclonus and pyramidal signs. PSW on EEG is rare and CSF 14-3-3 is positive in 80% of cases. 

The sCJDWl subtype has W at PrP codon 129 and type 1 PrP % and it accounts for 1% of the sporadic cases. The mean age at onset is 39 years and the mean clinical duration is 15 months. This younger age of clinical onset is unusual for a sporadic human prion disease and more closely resembles the age of onset that is characteristic in vCJD. This subtype shows dementia at the early clinical stages and is followed by myoclonus and pyramidal signs. There is no PSW on EEG and the CSF 14-3-3 is positive in all cases tested. 

The specific subtypes of the NnAChRs mediating the response of pulmonary sensory neurons to nicotine and their subunit compositions require further investigation. In view of the recent discoveries and developments of selective ligands targeting specific subunits of NnAChRs as the potential therapeutic interventions for neurodegenerative diseases (e.g., dementia) (Gatto et al. 2004 Ray et al. 2004), their possible side effects on pulmonary sensory nerves and airway irritation certainly merit further investigation. 

Neurochemical examination of biopsy and antopsy brain material from Alzheimer patients has revealed loss of the presynaptic marker enzymes acetyl coenzyme A (acetyl-CoA), chohne 6>-acetyltransferase and acetylcholinesterase (AChE), and of muscarinic receptor sites of the M2 subtype correlating with dementia score and severity of nenrohistopathology [8]. These alterations do, to some extent, reflect the well-documented neuronal cell loss in the nucleus of Meynert in presenile dementia and AD. Lesions of this brain nncleus in rats, a limited model for the cholinergic deficit of AD, resnlt in marked reductions in the levels of cholinergic en me markers in the neocortex accompanied by great decreases in the total muscarinic receptor levels [9,10]. 

Figure 46.2 Prevalence of subtypes of dementia. AD = Alzheimer s disease DLB = Lewy body dementia FTD = frontotemporal dementia VaD = vascular dementia.

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