In the study, the AD research centre of Pittsburgh examined 1139 patients with probable AD between April 1983 and February 2000. They found several sub groups of AD with the sensitivity at 97% and the specificity at 80%. However, it was also found that from 1983 to 1989, the sensitivity was still high at 94% but the specificity was only 52%. The specificity increased from 1990 to 2000, to 88%. This was thought to be due to better diagnostic tools that detected other forms of dementia (e.g. vascular dementia, frontotemporal dementia, progressive supranuclear palsy and dementia with lewy bodies), separating them from what would have previously been a diagnosis of AD. This shows that although AD does show similar symptoms to other forms of dementia, better diagnostic tools have allowed these other forms to be identified. However, the study also shows that there are still many sub-types of AD and that the NINCDS-ARDA should be updated to recognise this. Also a second study, also by Lopez et. al (2000), showed comorbid conditions can affect cognition delineate clearly defined subgroups in AD. Later studies also show evidence of subtypes of AD.
These studies show that one subtype is AD with symptoms of psychosis (delusions or hallucinations). Hallucinations in AD were first described by Alzheimer himself in 1907. The records of this have been found and reported by Maurer, Volk and Gerbaldo (1997). According to the Alzheimer’s notes of his patient August D., one of the symptoms was that, ‘she felt that someone wanted to kill her began to scream loudly’ (p1548). The term ‘delusion’, however, refers to a variety of false beliefs, differing in form and content, each of which may require a different cognitive and neurobiological explanation (Frith, 1999). A study by Jeste and Finkel (2000) proposes criteria for the syndrome of psychosis in AD, since psychotic signs appear to represent a specific syndrome with longitudinal stability. In a more recent study by Shanks and Venneri (2002), the misidentification syndrome was investigated. One of the symptoms of the patients the patients showed was misidentifying objects (such as soft toys) as sentient beings and behavioural associations to that effect were observed. The study involved looking at three patient with AD using regional cerebral blood flow (rCBF), measurements with HMPO SPECT and a comprehensive clinical and neuropsychological assessment. It was found that the three patients showed a distinctive patter of rCBF with dysfunction centred in the right parietal area and sever visuospatial and visuoperceptive processing deficits. The patients also showed relatively preserved memory and language abilities.
This is important because one the major symptom that differentiates AD from other forms of dementia is memory deficits (as discussed earlier). It is also interesting because the patients in this study were in the early stages of illness. As discussed earlier, it is important to identify early characteristics of AD for appropriate diagnosis and prognosis of the patient. This possible subtype of AD would also allow for a clearer distinction between AD and dementia with lewy bodies (where hallucinations are a major characteristic).
A later paper by Sultzer et. al (2003), looked into the relationship of AD with psychosis and regional cortical metabolism in patients with AD. The study involved conducting PET scans on 25 patients with probable AD (not on psychotropic medication). The severity of the delusions was assessed using a semi-structured interview and the Neurobehavioral Rating Scale. The findings indicated that the severity of delusions was associated with hypometabolism in additional prefrontal and anterior cingulated regions. Although this research is useful in determining a link between the psychosis syndrome and regional brain functioning, there are methodological problems. Firstly, the study focused on metabolic rates in certain regions of the brain, on the basis on previous findings. This meant that associations between the severity of delusions and metabolic activity elsewhere in the brain. Additionally the limited number of participants limited the number of effects that could be observed. Finally, it could not be determined whether regional metabolic rates are a cause or an effect of delusional thoughts in AD.
A study in the same year (Cook et al., 2003) looked at psychotic symptoms in AD to investigate whether AD with psychosis was homogenous or a composite of subtypes. According to Cook et. al there are many types of delusions reported in AD. These include delusions or persecution, delusions of infidelity, delusions of abandonment, and delusions that deceased individuals are still living. In addition to these symptoms, a set of misidentification delusions are frequent in AD patients. The study used records of patients diagnosed with possible or probable AD and had at least one psychotic symptom. The occurrence of psychotic symptoms was subjected to an exploratory factor analysis. The results showed that misidentification/hallucinations and persecutory delusions might identify two sub types of psychosis with AD. This was discussed to be contrary to earlier studies (Rubin et. al, 1988) proposing to classify AD with psychosis into three further categories (delusions, misidentification syndromes, and hallucinations) based on qualitatively similar phenomenomology. There are also limitations to this study. Firstly, the CBRS rating data was obtained at baseline visit of each patient. In addition, patients were a convenience sample obtained AD research centre clinic and therefore may not be representative of the AD population.
A further study by Cook et. al (2004) looked at these subtypes and whether they have any different patterns of cognitive impairment, compared with AD patients without psychosis. The findings showed that the misidentification group did not differ from the non-psychotic group on tests of verbal fluency and visuospatial function. The paranoid group did not differ from the non –psychotic group on any test. This therefore provided further support for the identification of misidentification and paranoid groups as distinct subgroups of AD with psychosis. However, when MMSE scores were added into the analyses as a covariate, the significant associations failed to persist.
From these studies into psychosis in AD, it is clear that there needs to be a further look at the criteria for diagnosis of AD in the NINCDS-ARDA. Although there is evidence for subtypes of psychosis, the methodological problems warrant further study before these can be accepted generally.
Several studies have demonstrated that the great majority of Alzheimer’s disease (AD) patients suffer "non-cognitive" neuropsychiatric symptoms. As discussed earlier (with reference to the NINCDS-ARDA criteria), there are other associated symptoms with AD. According to Hochang and Constantine (2003), depression affects up to 50% of AD patients and is associated with serious negative consequences for the patient and their caregivers. Although depression is thought to be a negative symptoms of AD (one that does not clearly distinguish it from many other causes), its impact on the patient warrants further study so appropriate treatments can be constructed. Furthermore, it is suggested by Hochang and Constantine that the diagnosis of depression in AD is difficult because many of the characteristics of depression which overlap with other manifestations of dementia (eg. apathy).
Recently, the National Institute of Mental Health (NIMH) convened the Depression of Alzheimer’s Disease Workgroup, which proposed provisional diagnostic criteria for depression of Alzheimer’s Disease (NIMH-dAD). It was decided that depression specific to AD often differs in its features and course from major depressive disorder in the DSM-IV (APA, 2000). It was also stated that there are at least 4 sub-types of depression in AD patients including; 1) depression in AD as an adjustment disorder with depressed mood, 2) depression in AD as a recurrence of early and mid life major an minor depressive disorder, 3) depression in AD as vascular depression and 4) depression in AD as part of a general medical condition (i.e. AD). According to Hochang and Constantine (2003), further studies need to be conducted to create a permanent criteria for depression in AD along with specification of possible sub-types, specific to the disease. Perhaps some of the causes of the neuropsychiatric symptoms in AD may then be revealed and create additional or alternative methods of treatment.
As discussed earlier, a variety of neuropsychiatric symptoms occur in AD including agitation, psychosis, depression, apathy, disinhibition, anxiety, purposeless behavior, and disorders of sleep and appetite. According to Cummings and Black (1998), neuropsychiatric symptoms have been related to cholinergic deficiency and improve after treatment with cholinomimetic agents. They go further to say that these observations provide the basis for the cholinergic hypothesis of the neuropsychiatric symptoms of AD, suggesting that the cholinergic deficit of AD contributes to the neuropsychiatric symptoms of AD and that cholinomimetic therapy ameliorates the behavioral disturbances accompanying AD. Furthermore, another study by Francis et. al (1999) into the progress of the cholinergic hypothesis showed that Donepezil produced improvement or no deterioration in more than 80% of AD patients. However, the same study also produced improvement or no deterioration in 59% patients on placebo. Therefore, it is difficult to rely on the cholinergic hypothesis at present, without further study. Nonetheless, there is an obvious need for further study due to the positive effects on patients’ symptoms.
Another common theory on the cause of symptoms of AD is neurofibrillary tangles. However, there have been few studies examining the relationship, if any, of neurofibrillary tangles and psychosis in AD. One such study was conducted by Farber et. al (2000). The study followed 109 subjects with AD longitudinally with semi-structured assessments, in order to assign a Clinical Dementia Rating and determine whether psychosis was present. After the subjects dies their brains were obtained for histological examination. The results showed that psychosis occurred commonly in AD patients, as found in 63% of those investigated. Additionally, subjects with psychosis had a 2.3-fold greater density of neocortical neurofibrillary tangles than the subjects without psychosis. The increase was independent of dementia severity. It was suggested that some common underlying process or processes specific to AD might regulate both phenomena (i.e. neurofibrillary tangles and psychosis). However further investigation is needed to see if this is a common occurrence in AD patients and to determine is there is a causal relationship between the two phenomena. It is difficult to investigate this as the patient must be deceased for investigation such as this to be carried out. Furthermore, it may be interesting to see whether this effect occurs cross-culturally.
According to Chow et. al (2002) the prevalence of Alzheimer's disease is similar across ethnic groups. However, they also state that there have been few cross-cultural studies into behavioural symptoms. The study compared neuropsychiatric symptoms of Chinese and American patients with AD. It was found that caregivers of the Chinese samples reported more anxiety and delusions than Americans. The caregivers of the Americans reported more appetite changes and apathy than the Chinese. This shows that there are behavioural differences in AD cross-culturally.
Overall, these studies show that there is still much need for further study into the neuropsychiatric symptoms of Alzheimer’s disease. The current studies show that there are important symptoms that may warrant a change in criteria for AD to incorporate additional subtypes. However, the problems that the current studies have faced include relying on previous work, limited selection of participants and reliance on post-mortem for confirmation. Future studies might benefit from using cross-cultural studies and longitudinal observations from representatives samples. From this, a better understanding of AD can be established delivering a better prognosis for the sufferers.
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