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NEUROPRACTOPIN   |    
Phenomenological Distinctions Needed in DSM-V: Delirium, Subsyndromal Delirium, and Dementias
David Meagher, M.D., M.R.C.Psych.; Paula T. Trzepacz, M.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 2007;19:468-470.
View Author and Article Information

Dr. Meagher is affiliated with the Department of Adult Psychiatry, Midwestern Regional Hospital, Limerick, Ireland. Dr. Trzepacz is affiliated with Indiana University School of Medicine and Lilly Research Laboratories, Indianapolis, Indiana. Address correspondence to Dr. Meagher, Department of Adult Psychiatry, Midwestern Regional Hospital, Limerick, Ireland; meaghermob@eircom.net (e-mail).

Copyright © 2007 American Psychiatric Publishing, Inc.

Prior to DSM-III, the diagnostic criteria to distinguish delirium and dementia were lacking. Research using DSM-III and subsequent versions has highlighted substantial comorbidity between these two major cognitive disorders with up to 89% of hospitalized dementia patients experiencing delirium.1 Though delirium negatively affects subsequent functional capacity and the trajectory of cognitive decline and is associated with increased morbidity and mortality, it is frequently underdiagnosed, especially in older patients, in whom symptoms overlapping with dementias can present diagnostic challenges. Neuropsychiatric symptoms are almost ubiquitous during the course of dementia,2 but the role of unrecognized comorbid delirium in causing or exacerbating these symptoms has received limited attention, despite the heightened vulnerability to deliriogenic factors (e.g., anticholinergic medication effects) in dementia populations.

Various evidence suggests that psychotic symptoms in dementia may be due to unrecognised superimposed delirium. Two patterns in the course of psychotic symptoms in Alzheimer’s disease contrast: persistence with treatment resistance versus relative transience, the latter consistent with delirious states.3 Recent factor analytical studies indicate distinct phenomenological patterns to psychosis in Alzheimer’s disease—hallucinations and misidentifications which correlate with cognitive impairment, and persecutory delusions that relate more closely to mood disturbances or other factors, such as delirium.4,5 The risk of psychosis in both delirium and Alzheimer’s disease is related to the magnitude of medical morbidity6,7—a risk factor for delirium, as well as with COMT (catechol-O-methyltransferase) genetic variations.8,9 Moreover, dementia complicated by psychosis evidences generalized slowing on electroencephalography (EEG) comparable to that in delirium and is independent of dementia severity.10

The traditional distinction between delirium and dementia, according to acuteness of onset and temporal course, is less clear in those elderly who develop "persistent cognitive impairment" following an episode of delirium11 or experience the fluctuating symptom pattern of Lewy Body Dementia (LBD). Delirium may be the harbinger of an underlying undiagnosed dementia,12 or persistent cognitive deficits may relate to medical problems that caused delirium (e.g., hypoxemia, encephalitis), medication effects, consequences of inability to cooperate with treatments, or direct neurotoxicity of delirium. DSM-IV describes a circularity in delirium-dementia differentiation: delirium is the suggested diagnosis when cognitive changes "are not better accounted for by a preexisting, established or evolving dementia;" dementia is the suggested diagnosis when "deficits do not occur exclusively during the course of a delirium." Further, subsyndromal delirium is not recognized in DSM-IV-TR, nor are guidelines offered for when postdelirium cognitive impairment is better attributed to dementia.

DSM-V can provide more clarity regarding differential diagnosis and comorbidity by addressing relative frequencies and characteristics of individual symptoms, including further phenomenological delineation of dementia types, and by increasing awareness of symptoms possibly related to subsyndromal delirium. It is underappreciated that delirium symptoms predominate dementia symptoms when they are comorbid, but present with more impaired cognitive scores13 or more disorganized thinking and disorientation.14 These studies lend credence to the clinical dictum to "assume delirium until proven otherwise." Careful history-taking and use of sensitive and specific delirium assessment instruments (e.g., DRS-R98) can reliably distinguish delirium from dementia.

Neuropsychiatric symptom patterns also assist differentiation. In Alzheimer’s disease, attentional abilities are relatively spared compared with LBD and delirium.15 Blinded ratings of delirium and dementia cases found greater impairment in delirium for disturbances of attention, visuospatial ability, the sleep-wake cycle, perception, thought process, affective lability, motor agitation, comprehension, and acuity of onset and fluctuation of symptoms.16 EEG findings can further aid differential diagnosis, especially with prion-induced dementias and LBD.

Criteria exist for differentiating psychosis of Alzheimer’s disease from functional psychoses17 but are less clear regarding delirium, although differences exist. Delusions in delirium typically involve paranoia about immediate well-being or perceived danger in the environment, whereas delusions in Alzheimer’s disease commonly reflect themes of being robbed or abandoned or are really misidentifications.4 Formal thought disorder in delirium frequently involves illogicality and derailment compared with the poverty of thought in dementia.18 Visual illusions and hallucinations are most common in delirium and LBD, compared with Alzheimer’s disease where careful interviewing is needed to differentiate complex visual hallucinations from delusions or confabulations. Tactile hallucinations and formication are highly suggestive of delirium.

Psychosis in Alzheimer’s disease correlates with the rate and severity of cognitive decline, especially seen in disturbances of attention, construction, and fluency.19 In contrast, studies of delirium suggest no correlation between cognition and psychosis.20 Moreover, psychosis is related to structural neuropathological changes in Alzheimer’s disease,21 whereas psychosis in delirium may reflect neurochemical changes associated with particular etiologies. APOE genotype and premorbid schizotypal features are risk factors for psychosis in Alzheimer’s disease but not in delirium.2224

Psychotic symptoms in delirium respond well to neuroleptics,25,26 but less so in Alzheimer’s disease, reflecting the relatively greater increase in central dopaminergic function that occurs with delirium.27 Cholinergic agents are mainstays for Alzheimer’s disease treatment, and chronic prophylaxis with rivastigmine in vascular dementia reduces delirium incidence.28 Cholinergic agents show some promise in treating delirium.29 We hypothesize that neuropsychiatric symptom improvement in dementia using neuroleptics or cholinergic agents may be partly attributable to treating or preventing a component of delirium.

DSM remains the gold standard for research diagnoses and therefore its specificity in differentiating delirium and dementia is crucial to efforts to illuminate the neuropsychiatry of these disorders. We propose that 1) dementia research needs to assess more carefully any delirium component and utilize instruments that capture characteristics that differentiate these disorders (e.g., the Delirium Rating Scale—Revised); 2) the differing courses of delirium symptoms (acute transient versus recurring versus persistent improving/not improving) should be categorized; 3) DSM-V should include phenomenological detail about syndromal and subsyndromal delirium, including relative frequency of all core and associated symptoms; 4) DSM-V should include phenomenological detail and relative frequency of symptoms for major types of dementias; and 5) DSM-V should more strongly encourage differential diagnosis of delirium and subsyndromal delirium in the dementia sections as possible reasons for the clinical presentation during the course of illness or responsiveness to treatments.

.
Fick DM, Agostini JV, Inouye SK: Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc 2002; 50:1723—1732
 
.
Aalten P, de Vugt ME, Jaspers N, et al: The course of neuropsychiatric symptoms in dementia, part I: findings from the two-year longitudinal maasbed study. Int J Ger Psychiatry 2005; 20:523—530
 
.
Ballard C, O’Brien J, Coope B, et al: A prospective study of psychotic symptoms in dementia sufferers: psychosis in dementia. Int Psychogeriatrics 1997; 9:57—64
 
.
Perez-Madrinan G, Cook SE, Saxton JA, et al: Alzheimer disease with psychosis: excess cognitive impairment is restricted to the misidentification subtype. Am J Geriatr Psychiatry 2004; 12:449—456
 
.
Wilkosz PA, Miyahara S, Lopez OL, et al: Prediction of psychosis onset in Alzheimer disease: the role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes. Am J Geriatr Psychiatry 2006; 14:352—356
 
.
Webster R, Holroyd S: Prevalence of psychotic symptoms in delirium. Psychosomatics 2000; 41:519—522
 
.
Bassiony MM, Steinberg MS, Warren A, et al: Delusions and hallucinations in Alzheimer’s disease: prevalence and clinical correlates. Int J Geriatr Psychiatry 2000; 15:99—107
 
.
Sweet RA, Devlin B, Pollock BG, et al: Catechol-O-methytransferase haplotypes are associated with psychosis in Alzheimer disease. Mol Psychiatry 2005; 10:1026—1036
 
.
Nakamura A, Inada T, Kitao Y, et al: Association between catechol-O-methyltransferase (COMT) polymorphism and severe alcoholic withdrawal symptoms in male Japanese alcoholics. Addict Biol 2001; 6:233—238
 
.
Edwards-Lee T, Cook I, Fairbanks L, et al: Quantitative electroencephalographic correlates of psychosis in Alzheimer disease. Neuropsychiatry Neuropsychol Behav Neurol 2000; 13:163—170
 
.
Wacker P, Nunes PV, Cabrita H, et al: Post-operative delirium is associated with poor cognitive outcome and dementia. Dem Geriatr Cogn Disord 2006; 21:221—227
 
.
Koponen H, Sirvio J, Lepola U, et al: A long-term follow-up study of cerebrospinal fluid acetylcholinesterase in delirium. Eur Arch Psychiatry Clin Neurosci 1994; 243:347—351
 
.
Trzepacz PT, Mulsant BH, Dew MA, et al: Is delirium different when it occurs in dementia? a study using the Delirium Rating Scale. J Neuropsychiatry Clin Neurosci 1998; 10:199—204
 
.
Cole MG, McCusker J, Dendukuri N, et al: Symptoms of delirium among elderly medical inpatients with or without dementia. J Neuropsychiatry Clin Neurosci 2002; 14:167—175
 
.
Calderon J, Perry RJ, Erzinclioglu SW, et al: Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2001; 70:157—164
 
.
Trzepacz PT, Mittal D, Torres R, et al: Delirium vs dementia symptoms: Delirium Rating Scale-Revised (DRS-R-98) and Cognitive Test for Delirium (CTD) item comparisons. Psychosomatics 2002; 43:156—157
 
.
Jeste DV, Finkel SI: Psychosis of Alzheimer’s disease and related dementias: diagnostic criteria for a distinct syndrome. Am J Geriatr Psychiatry 2000; 8:29—34
 
.
Cole MG: Delirium in elderly patients. Am J Geriatr Psychiatry 2004; 12:7—21
 
.
Paulsen JS, Salmon DP, Thal LJ, et al: Incidence of and risk factors for hallucinations and delusions in patients with probable AD. Neurol 2000; 54:1965—1971
 
.
Meagher DJ, Moran M, Raju B, et al: Phenomenology of delirium: assessment of 100 adult cases using standardized measures. Br J Psychiatry 190:135—141
 
.
Farber NB, Rubin EH, Newcomer JW, et al: Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry 2000; 57:1165—1173
 
.
Eror EA, Lopez OL, Dekosky ST, et al: Alzheimer disease subjects with psychosis have increased schizotypal symptoms before dementia onset. Biol Psychiatry 2005; 58:325—330
 
.
Bassiony MM, Lyketsos CG: Delusions and hallucinations in Alzheimer’s disease: review of the brain decade. Psychosomatics 2003; 44:388—401
 
.
Van Munster BC, Kaorevaar JC, de Rooij SE, et al: The association between delirium and APOE-epsilon 4 allelle in the elderly. Int Psychogeriatrics 2005; 17(suppl 2):149
 
.
Breitbart W, Marotta R, Platt MM, et al: A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatry 1996; 153:231—237
 
.
Breitbart W, Tremblay A, Gibson C: An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics 2002; 43:175—182
 
.
Van der Cammen TJM, Tiemeier H, Engelhart MJ, et al: Abnormal neurotransmitter metabolite levels in Alzheimer patients with a delirium. Int J Geriatr Psychiatry 2006; 21:838—843
 
.
Moretti R, Torre P, Antonello RM, et al: Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: a controlled, open 24-month study of 246 patients. Am J Alzheimers Dis Other Demen 2004; 19:333—339
 
.
Diaz V, Rodriguez J, Barrientos P, et al: Use of procholinergics in the prevention of postoperative delirium in hip fracture surgery in the elderly: a randomized controlled trial. Rev Neurol 2001; 33:716—719
 
+

References

.
Fick DM, Agostini JV, Inouye SK: Delirium superimposed on dementia: a systematic review. J Am Geriatr Soc 2002; 50:1723—1732
 
.
Aalten P, de Vugt ME, Jaspers N, et al: The course of neuropsychiatric symptoms in dementia, part I: findings from the two-year longitudinal maasbed study. Int J Ger Psychiatry 2005; 20:523—530
 
.
Ballard C, O’Brien J, Coope B, et al: A prospective study of psychotic symptoms in dementia sufferers: psychosis in dementia. Int Psychogeriatrics 1997; 9:57—64
 
.
Perez-Madrinan G, Cook SE, Saxton JA, et al: Alzheimer disease with psychosis: excess cognitive impairment is restricted to the misidentification subtype. Am J Geriatr Psychiatry 2004; 12:449—456
 
.
Wilkosz PA, Miyahara S, Lopez OL, et al: Prediction of psychosis onset in Alzheimer disease: the role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes. Am J Geriatr Psychiatry 2006; 14:352—356
 
.
Webster R, Holroyd S: Prevalence of psychotic symptoms in delirium. Psychosomatics 2000; 41:519—522
 
.
Bassiony MM, Steinberg MS, Warren A, et al: Delusions and hallucinations in Alzheimer’s disease: prevalence and clinical correlates. Int J Geriatr Psychiatry 2000; 15:99—107
 
.
Sweet RA, Devlin B, Pollock BG, et al: Catechol-O-methytransferase haplotypes are associated with psychosis in Alzheimer disease. Mol Psychiatry 2005; 10:1026—1036
 
.
Nakamura A, Inada T, Kitao Y, et al: Association between catechol-O-methyltransferase (COMT) polymorphism and severe alcoholic withdrawal symptoms in male Japanese alcoholics. Addict Biol 2001; 6:233—238
 
.
Edwards-Lee T, Cook I, Fairbanks L, et al: Quantitative electroencephalographic correlates of psychosis in Alzheimer disease. Neuropsychiatry Neuropsychol Behav Neurol 2000; 13:163—170
 
.
Wacker P, Nunes PV, Cabrita H, et al: Post-operative delirium is associated with poor cognitive outcome and dementia. Dem Geriatr Cogn Disord 2006; 21:221—227
 
.
Koponen H, Sirvio J, Lepola U, et al: A long-term follow-up study of cerebrospinal fluid acetylcholinesterase in delirium. Eur Arch Psychiatry Clin Neurosci 1994; 243:347—351
 
.
Trzepacz PT, Mulsant BH, Dew MA, et al: Is delirium different when it occurs in dementia? a study using the Delirium Rating Scale. J Neuropsychiatry Clin Neurosci 1998; 10:199—204
 
.
Cole MG, McCusker J, Dendukuri N, et al: Symptoms of delirium among elderly medical inpatients with or without dementia. J Neuropsychiatry Clin Neurosci 2002; 14:167—175
 
.
Calderon J, Perry RJ, Erzinclioglu SW, et al: Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2001; 70:157—164
 
.
Trzepacz PT, Mittal D, Torres R, et al: Delirium vs dementia symptoms: Delirium Rating Scale-Revised (DRS-R-98) and Cognitive Test for Delirium (CTD) item comparisons. Psychosomatics 2002; 43:156—157
 
.
Jeste DV, Finkel SI: Psychosis of Alzheimer’s disease and related dementias: diagnostic criteria for a distinct syndrome. Am J Geriatr Psychiatry 2000; 8:29—34
 
.
Cole MG: Delirium in elderly patients. Am J Geriatr Psychiatry 2004; 12:7—21
 
.
Paulsen JS, Salmon DP, Thal LJ, et al: Incidence of and risk factors for hallucinations and delusions in patients with probable AD. Neurol 2000; 54:1965—1971
 
.
Meagher DJ, Moran M, Raju B, et al: Phenomenology of delirium: assessment of 100 adult cases using standardized measures. Br J Psychiatry 190:135—141
 
.
Farber NB, Rubin EH, Newcomer JW, et al: Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry 2000; 57:1165—1173
 
.
Eror EA, Lopez OL, Dekosky ST, et al: Alzheimer disease subjects with psychosis have increased schizotypal symptoms before dementia onset. Biol Psychiatry 2005; 58:325—330
 
.
Bassiony MM, Lyketsos CG: Delusions and hallucinations in Alzheimer’s disease: review of the brain decade. Psychosomatics 2003; 44:388—401
 
.
Van Munster BC, Kaorevaar JC, de Rooij SE, et al: The association between delirium and APOE-epsilon 4 allelle in the elderly. Int Psychogeriatrics 2005; 17(suppl 2):149
 
.
Breitbart W, Marotta R, Platt MM, et al: A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. Am J Psychiatry 1996; 153:231—237
 
.
Breitbart W, Tremblay A, Gibson C: An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics 2002; 43:175—182
 
.
Van der Cammen TJM, Tiemeier H, Engelhart MJ, et al: Abnormal neurotransmitter metabolite levels in Alzheimer patients with a delirium. Int J Geriatr Psychiatry 2006; 21:838—843
 
.
Moretti R, Torre P, Antonello RM, et al: Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: a controlled, open 24-month study of 246 patients. Am J Alzheimers Dis Other Demen 2004; 19:333—339
 
.
Diaz V, Rodriguez J, Barrientos P, et al: Use of procholinergics in the prevention of postoperative delirium in hip fracture surgery in the elderly: a randomized controlled trial. Rev Neurol 2001; 33:716—719
 
+
+

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