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Antipsychotics and their impact on cognition in the elderly
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BIOL. PSYClUATRY 1991;42:IS-mS
01 soluble TNF receptors known to suppress nonREM sleep In animals. ~F·lnduced
increases In plasma TNF-a levels occur later during the night and are paralled by a tendency to a rebound of SWS, suggesting that, In humans. TNF-a increases slow wave sleep whereas antagonism of Its biological activity suppress SWS. In conclusion, our findings suggest that Infections affect human sleep primarily due to Increases in the systemic levels of cytoklnes such as TNF-a. The restriction 01 Increases In nonREM sleep amount and Intensity to low degrees of host defense activation may Indicate that the supposed Immuno-supportive role of SWS is confined to the initial (or final) phases of acute infection. Reference. [1) Krueger J.M., Takahashi S., Kapas L al aI. (1995): Cyloklnes In sleep regulalion. Adv Neurolmmunol5: 171-188. (2) PollmAcher T., MulWnton J., Korth C., Hlnze-Selch O. (1995): Innuance 01 host defense activation on sleep In humans. Adv Neurolmmunol 5: 155-169. [3J PollmAcher T., Korth C., Mulling10n J. at al. (1996): Enects of granulocyle colony·atim• ulatlng factor on plasma cytolone and cytoklne receptor Iavels and on the In vivo host response to endotoxin In humans. Blood 87:900-905.
6. The elderly and psychosis ~
Psychosis In the elderly
M. Davidson. Division of Psychiatry, The Chalm Sheba Medical Center, Te/·Hashomer, Israel Normal penception, judgement and thought processing are partially depen• dent upon preservation of rnetT1OIY, leamlng and attention. Thus elderty palients suffering from schizophrenia or degenerative dementias such as Alzheimer's, Pick's, Parldnson's and Lewy body disease often manilest both psychosis and cognitlve Impairment. Despite the phenomenological c0m• munality, post-mortem studies have failed to determine a common biological substrate for the degenerative dementias and psychosis. Nevertheless, both psychosis and cognitive Impairment contribute to the social deterioration of these patients. In schizophrenia, the severity 01 psychosis remains stable or Improves lightly over tine course of tine Illness. Cognitive impairment, on the other hand. gradually worsens. In tine dementlas, cognitive impairment and psychosis aggravate In parallel. Symptomatic treatment of either psychosis or cognitive impairment can improve the other and delay social deteriora• tion. Cholinomimetic drugs may delay cognitive decline In some patients with dementia and may ameliorate hallucinations. Conventional neurolep• tlcs ameliorate psychosis In elderly individuals suffering from dementia or schizophrenia and novel antipsychotics appear also to benefit cognitive func• tion In some elderiy patients suffering from psychosis. Unfortunately elderty Individuals suffering from dementia or psychosis are particularty vulnerable to the extrapyramidal side effects (EPS) 01 antipsychotic medication. It is therefore essential that antipsychotic drugs given to this group ot patients should have minlmal EPS liability.
16-21 Late onset psyChosis: diagnosis and treatment P.V. Rablns. Department of Psychiatry BIld Behavioral Sciences. Baltimore. USA Emile Kraepelin recognised that some patients with a schlzophrenia-like syndrome did not dilapidate In personality and he labelled this condition paraphrenia The term was resurrected In the ear1y 19505 by Martin Roth and applied to a condition which was charactarised by prorninen1 halluci• nations and delusions. no avldence of mood or cognitive disorder and later Ule onset Recent research suggests that lat~set psychosis Is a hetero• geneous disorder. Some patients have predominantly delusions and fulfil criteria for delusional disorder. A significant proportion of these Individuals deteriorate cognitlvely and later receive a diagnosis 01 dementia. Patients In 8 second group, with prominent halluclnations and delusions Including first rank symptoms, do not decline cognltively and have a treatment response and course more similar to that of schizophrenia. Risk factor for the latter psychosis Include female sex, hearing Impairment. premorbld Isolation and a slightly Increased family history of schizophrenia. Randomised control
The elderly and psychosis
trials are not available, but case studies suggest this disorder responds to neuroleptic treatment at about the sarne rate as schizophrenia. How• ever, thought disorder and personality dilapidation generally do not OCCUr at follow-up, suggesting that the condition is not a perfect phenocopy for schizophrenia.
16-31 elderly Antlpsychotics and their Impact on cognition In the P.O. Harvey. Department of Psychiatry, 8aK '229, Mount Sinal School of Medicine, New ~ USA Cognitive Impairment Is one 01 the most important predictors of poor overall outcome in schizophrenia. Regardless 01 the age of the patient. those with greater cognitive impairment are more Impaired In their adaptive skills and more likely to receive care in highly structured and expensive settings, Such as long·stay psychiatric hospitals or nursing homes. Several specific aspects of cognitive functioning are more Important than others for the prediction of outcome, including memory functions, executive functioning, and attention. Treatment of both geriatric and nongeriatric popUlations with conventional neuroleptics has been found to be of limited value for Improving these aspects of cognitlve Impairment. Furthermore, medications used to treat the side effects of typical neuroleptics have exaggerated effects on cognitive functioning In elderly patients, leading to even more severe Impairments In memory functioning. Newer antipsychotlcs have shown considerable promise for remedIation ot cognitlve impairments, and have less adverse cognitive side effects than conventional neuroleptics. Data from a number of research groups have shown that attention, problem-solving, worldng memory, serial encoding and delayed recall memory are all ImproVed by treatment with novel antipsychotics. These data strongly suggest the use of novel antipsychotics for the treatment 01 psychosis In the elderty and Indicate that these medications have promise to produce beneficial and direct effects on cognitive functioning In elderty patients.
16-41 Classic and novel antlpsychotlcs In the elderly: efficacy and side effects D.V. Jeste, J.P. Lacro, M.J. Harris. E. Rockwell. University of Celifomia. San Diego and San Diego Veterans' Administration Medical Center, San Diego, CA. USA Cognitive Impairment In schizophrenia 18 an Integral feature 01 the diSOl'der and Its severity forecasts worse functional abilities. poorer prognosis, as well as a greater cost of care. Elderly patients with schizophrenia and other psychotic disorders treated with conventional neuroleptics are at an Increased risk of side effects, particularly tardive dyskinesia. The effects of conventional neuroleptics on cognitlon are variable. depending on the type of drug (loW potency vs. high potency), the dose, length of treatment, and the patienfs baseline level of cognitive deficit. The newer antipsychotics are more effective than conventional neuroleptlcs In the treatment of negative symptoms of schizophrenia and also produce less extrapyramidal Side effects (EPS). The literature on the use ot these drugs in the elderly Is Iimlled. Nevertheless, several studies suggest that risperidone, when uSed at appropriate doses (I.e. lower doses than are necessary for non-elderly patients with chronic schiZophrenia) may Improve some cognltive defiCits in older patients with psychotic disorders. It is not dear whether this Is a result 01 Its direct effects on cognition or an Indirect effect (e.g. by reduCing negative symptoms while producing fewer EPS, less sedation and confuSion compared to conventional neuroleptics). Nevertheless, Improved cognition In elderty patients wouid be a major benefit of the newer antlpsychotics.
BIOL. PSYClUATRY 1991;42:IS-mS
01 soluble TNF receptors known to suppress nonREM sleep In animals. ~F·lnduced
increases In plasma TNF-a levels occur later during the night and are paralled by a tendency to a rebound of SWS, suggesting that, In humans. TNF-a increases slow wave sleep whereas antagonism of Its biological activity suppress SWS. In conclusion, our findings suggest that Infections affect human sleep primarily due to Increases in the systemic levels of cytoklnes such as TNF-a. The restriction 01 Increases In nonREM sleep amount and Intensity to low degrees of host defense activation may Indicate that the supposed Immuno-supportive role of SWS is confined to the initial (or final) phases of acute infection. Reference. [1) Krueger J.M., Takahashi S., Kapas L al aI. (1995): Cyloklnes In sleep regulalion. Adv Neurolmmunol5: 171-188. (2) PollmAcher T., MulWnton J., Korth C., Hlnze-Selch O. (1995): Innuance 01 host defense activation on sleep In humans. Adv Neurolmmunol 5: 155-169. [3J PollmAcher T., Korth C., Mulling10n J. at al. (1996): Enects of granulocyle colony·atim• ulatlng factor on plasma cytolone and cytoklne receptor Iavels and on the In vivo host response to endotoxin In humans. Blood 87:900-905.
6. The elderly and psychosis ~
Psychosis In the elderly
M. Davidson. Division of Psychiatry, The Chalm Sheba Medical Center, Te/·Hashomer, Israel Normal penception, judgement and thought processing are partially depen• dent upon preservation of rnetT1OIY, leamlng and attention. Thus elderty palients suffering from schizophrenia or degenerative dementias such as Alzheimer's, Pick's, Parldnson's and Lewy body disease often manilest both psychosis and cognitlve Impairment. Despite the phenomenological c0m• munality, post-mortem studies have failed to determine a common biological substrate for the degenerative dementias and psychosis. Nevertheless, both psychosis and cognitive Impairment contribute to the social deterioration of these patients. In schizophrenia, the severity 01 psychosis remains stable or Improves lightly over tine course of tine Illness. Cognitive impairment, on the other hand. gradually worsens. In tine dementlas, cognitive impairment and psychosis aggravate In parallel. Symptomatic treatment of either psychosis or cognitive impairment can improve the other and delay social deteriora• tion. Cholinomimetic drugs may delay cognitive decline In some patients with dementia and may ameliorate hallucinations. Conventional neurolep• tlcs ameliorate psychosis In elderly individuals suffering from dementia or schizophrenia and novel antipsychotics appear also to benefit cognitive func• tion In some elderiy patients suffering from psychosis. Unfortunately elderty Individuals suffering from dementia or psychosis are particularty vulnerable to the extrapyramidal side effects (EPS) 01 antipsychotic medication. It is therefore essential that antipsychotic drugs given to this group ot patients should have minlmal EPS liability.
16-21 Late onset psyChosis: diagnosis and treatment P.V. Rablns. Department of Psychiatry BIld Behavioral Sciences. Baltimore. USA Emile Kraepelin recognised that some patients with a schlzophrenia-like syndrome did not dilapidate In personality and he labelled this condition paraphrenia The term was resurrected In the ear1y 19505 by Martin Roth and applied to a condition which was charactarised by prorninen1 halluci• nations and delusions. no avldence of mood or cognitive disorder and later Ule onset Recent research suggests that lat~set psychosis Is a hetero• geneous disorder. Some patients have predominantly delusions and fulfil criteria for delusional disorder. A significant proportion of these Individuals deteriorate cognitlvely and later receive a diagnosis 01 dementia. Patients In 8 second group, with prominent halluclnations and delusions Including first rank symptoms, do not decline cognltively and have a treatment response and course more similar to that of schizophrenia. Risk factor for the latter psychosis Include female sex, hearing Impairment. premorbld Isolation and a slightly Increased family history of schizophrenia. Randomised control
The elderly and psychosis
trials are not available, but case studies suggest this disorder responds to neuroleptic treatment at about the sarne rate as schizophrenia. How• ever, thought disorder and personality dilapidation generally do not OCCUr at follow-up, suggesting that the condition is not a perfect phenocopy for schizophrenia.
16-31 elderly Antlpsychotics and their Impact on cognition In the P.O. Harvey. Department of Psychiatry, 8aK '229, Mount Sinal School of Medicine, New ~ USA Cognitive Impairment Is one 01 the most important predictors of poor overall outcome in schizophrenia. Regardless 01 the age of the patient. those with greater cognitive impairment are more Impaired In their adaptive skills and more likely to receive care in highly structured and expensive settings, Such as long·stay psychiatric hospitals or nursing homes. Several specific aspects of cognitive functioning are more Important than others for the prediction of outcome, including memory functions, executive functioning, and attention. Treatment of both geriatric and nongeriatric popUlations with conventional neuroleptics has been found to be of limited value for Improving these aspects of cognitlve Impairment. Furthermore, medications used to treat the side effects of typical neuroleptics have exaggerated effects on cognitive functioning In elderly patients, leading to even more severe Impairments In memory functioning. Newer antipsychotlcs have shown considerable promise for remedIation ot cognitlve impairments, and have less adverse cognitive side effects than conventional neuroleptics. Data from a number of research groups have shown that attention, problem-solving, worldng memory, serial encoding and delayed recall memory are all ImproVed by treatment with novel antipsychotics. These data strongly suggest the use of novel antipsychotics for the treatment 01 psychosis In the elderty and Indicate that these medications have promise to produce beneficial and direct effects on cognitive functioning In elderty patients.
16-41 Classic and novel antlpsychotlcs In the elderly: efficacy and side effects D.V. Jeste, J.P. Lacro, M.J. Harris. E. Rockwell. University of Celifomia. San Diego and San Diego Veterans' Administration Medical Center, San Diego, CA. USA Cognitive Impairment In schizophrenia 18 an Integral feature 01 the diSOl'der and Its severity forecasts worse functional abilities. poorer prognosis, as well as a greater cost of care. Elderly patients with schizophrenia and other psychotic disorders treated with conventional neuroleptics are at an Increased risk of side effects, particularly tardive dyskinesia. The effects of conventional neuroleptics on cognitlon are variable. depending on the type of drug (loW potency vs. high potency), the dose, length of treatment, and the patienfs baseline level of cognitive deficit. The newer antipsychotics are more effective than conventional neuroleptlcs In the treatment of negative symptoms of schizophrenia and also produce less extrapyramidal Side effects (EPS). The literature on the use ot these drugs in the elderly Is Iimlled. Nevertheless, several studies suggest that risperidone, when uSed at appropriate doses (I.e. lower doses than are necessary for non-elderly patients with chronic schiZophrenia) may Improve some cognltive defiCits in older patients with psychotic disorders. It is not dear whether this Is a result 01 Its direct effects on cognition or an Indirect effect (e.g. by reduCing negative symptoms while producing fewer EPS, less sedation and confuSion compared to conventional neuroleptics). Nevertheless, Improved cognition In elderty patients wouid be a major benefit of the newer antlpsychotics.