Worsening cognitive impairment and neurodegenerative pathology progressively increase risk for delirium.

BACKGROUND: Delirium is a profound neuropsychiatric disturbance precipitated by acute illness. Although dementia is the major risk factor this has typically been considered a binary quantity (i.e., cognitively impaired versus cognitively normal) with respect to delirium risk. We used humans and mice to address the hypothesis that the severity of underlying neurodegenerative changes and/or cognitive impairment progressively alters delirium risk. METHODS: Humans in a population-based longitudinal study, Vantaa 85+, were followed for incident delirium. Odds for reporting delirium at follow-up (outcome) were modeled using random-effects logistic regression, where prior cognitive impairment measured by Mini-Mental State Exam (MMSE) (exposure) was considered. To address whether underlying neurodegenerative pathology increased susceptibility to acute cognitive change, mice at three stages of neurodegenerative disease progression (ME7 model of neurodegeneration: controls, 12 weeks, and 16 weeks) were assessed for acute cognitive dysfunction upon systemic inflammation induced by bacterial lipopolysaccharide (LPS; 100 µg/kg). Synaptic and axonal correlates of susceptibility to acute dysfunction were assessed using immunohistochemistry. RESULTS: In the Vantaa cohort, 465 persons (88.4 ± 2.8 years) completed MMSE at baseline. For every MMSE point lost, risk of incident delirium increased by 5% (p = 0.02). LPS precipitated severe and fluctuating cognitive deficits in 16-week ME7 mice but lower incidence or no deficits in 12-week ME7 and controls, respectively. This was associated with progressive thalamic synaptic loss and axonal pathology. CONCLUSION: A human population-based cohort with graded severity of existing cognitive impairment and a mouse model with progressing neurodegeneration both indicate that the risk of delirium increases with greater severity of pre-existing cognitive impairment and neuropathology.

Delirium is a strong risk factor for dementia in the oldest-old: a population-based cohort study.

Recent studies suggest that delirium is associated with risk of dementia and also acceleration of decline in existing dementia. However, previous studies may have been confounded by incomplete ascertainment of cognitive status at baseline. Herein, we used a true population sample to determine if delirium is a risk factor for incident dementia and cognitive decline. We also examined the effect of delirium at the pathological level by determining associations between dementia and neuropathological markers of dementia in patients with and without a history of delirium. The Vantaa 85+ study examined 553 individuals (92% of those eligible) aged ≥85 years at baseline, 3, 5, 8 and 10 years. Brain autopsy was performed in 52%. Fixed and random-effects regression models were used to assess associations between (i) delirium and incident dementia and (ii) decline in Mini-Mental State Examination scores in the whole group. The relationship between dementia and common neuropathological markers (Alzheimer-type, infarcts and Lewy-body) was modelled, stratified by history of delirium. Delirium increased the risk of incident dementia (odds ratio 8.7, 95% confidence interval 2.1-35). Delirium was also associated with worsening dementia severity (odds ratio 3.1, 95% confidence interval 1.5-6.3) as well as deterioration in global function score (odds ratio 2.8, 95% confidence interval 1.4-5.5). In the whole study population, delirium was associated with loss of 1.0 more Mini-Mental State Examination points per year (95% confidence interval 0.11-1.89) than those with no history of delirium. In individuals with dementia and no history of delirium (n = 232), all pathologies were significantly associated with dementia. However, in individuals with delirium and dementia (n = 58), no relationship between dementia and these markers was found. For example, higher Braak stage was associated with dementia when no history of delirium (odds ratio 2.0, 95% confidence interval 1.1-3.5, P = 0.02), but in those with a history of delirium, there was no significant relationship (odds ratio 1.2, 95% confidence interval 0.2-6.7, P = 0.85). This trend for odds ratios to be closer to unity in the delirium and dementia group was observed for neuritic amyloid, apolipoprotein ε status, presence of infarcts, α-synucleinopathy and neuronal loss in substantia nigra. These findings are the first to demonstrate in a true population study that delirium is a strong risk factor for incident dementia and cognitive decline in the oldest-old. However, in this study, the relationship did not appear to be mediated by classical neuropathologies associated with dementia.

[The treatment pathway of a memory disorder patient]. / Muistipotilaan hoitoketju.

The treatment of a memory disorder patient is multiprofessional teamwork requiring professional personnel specialized in memory disorders. The memory disorder clinic plays a central role especially at the diagnostic stage. Treatment should be carried out as local services and according to the needs of the patients. A memory coordinator is a central person in the monitoring and supporting of a memory patient and his/her close relatives within outpatient care. In long-term therapy, know-how in rehabilitation and palliative treatment are essential. Development of the treatment and service chain requires capable management, systematic planning, regular updating of guidelines and contracts as well as financial input.

The association of the dopamine transporter gene and the dopamine receptor 2 gene with delirium, a meta-analysis.

Delirium is the most common neuropsychiatric syndrome in elderly ill patients. Previously, associations between delirium and the dopamine transporter gene (solute carrier family 6, member 3 (SLC6A3)) and dopamine receptor 2 gene (DRD2) were found. The aim of this study was to validate whether markers of the SLC6A3 and DRD2 genes are were associated with delirium in independent populations. Six European populations collected DNA of older delirious patients. Associations were determined per population and results were combined in a meta-analysis. In total 820 medical inpatients, 185 cardiac surgery patients, 134 non-cardiac surgery patients and 502 population-based elderly subjects were included. Mean age was 82 years (SD 7.5 years), 598 (36%) were male, 665 (41%) had pre-existing cognitive impairment, and 558 (34%) experienced delirium. The SLC6A3 rs393795 homozygous AA genotype was more frequent in patients without delirium in all populations. The meta-analysis showed an Odds Ratio (OR) for delirium of 0.4 (95% confidence interval (C.I.) 0.2-0.6, P = 0.0003) for subjects with AA genotype compared to the AG and GG genotypes. SLC6A3 marker rs1042098 showed no association with delirium. In meta-analysis the DRD2 rs6276 homozygous GG genotype showed an OR of 0.8 for delirium (95% C.I. 0.6-1.1, P = 0.24). When subjects were stratified for cognitive status the rs6276 GG genotype showed ORs of 0.6 (95% C.I. 0.4-1.0, P = 0.06) and 0.8 (95% C.I. 0.5-1.5, P = 0.51) for delirium in patients with and without cognitive impairment, respectively. In independent cohorts, a variation in the SLC6A3 gene and possibly the DRD2 gene were found to protect for delirium.

The use of psychotropics and survival in demented elderly individuals.

The present study aimed to examine the use of psychotropics and its relation to survival in demented elderly persons. A random sample of 700 individuals, aged 75 years or older, was drawn from the population of Kuopio city in January 1998. A geriatrician and a nurse carried out clinical examinations of 601 individuals, of whom 137 suffered from dementia according to DSM-IV criteria. The lifespan was calculated from the date of examination in 1998 to the end of 2003. In survival analyses, subjects were divided according to psychotropic use into groups: (i) users of only one of kind of psychotropics and (ii) concomitant users of all kinds of psychotropics. Psychotropics were classified into antipsychotics, antidepressants and a group of anxiolytics and hypnotics/sedatives. Seventy-one percent (n = 97) of demented elderly individuals used a psychotropic drug. Age- and sex-adjusted survival did not differ by severity of dementia (P = 0.076) or by the diagnosis of dementia (P = 0.54). When survival was compared with nonusers of psychotropics, the hazard ratio was 2.75 (P = 0.002) for individuals who used antipsychotics as their only psychotropic medicine and 1.76 (95% confidence interval 1.09-2.86) for concomitant users of all kinds of psychotropics. The use of several psychotropics or antipsychotics is a risk factor for death in demented elderly persons.

Use of psychotropics among home-dwelling nondemented and demented elderly.

OBJECTIVE: To describe the use of psychotropics in the nondemented and demented elderly. PARTICIPANTS: The home-dwelling elderly (n=523) among the random sample of 700 subjects from the total population of individuals aged 75 years or more in 1998 and living in the city of Kuopio, Finland. METHODS: A trained nurse interviewed the participants about their health and current use of medicines. A geriatrician performed clinical examinations and diagnosed diseases. Dementia and depression were diagnosed according to the DSM-IV criteria. RESULTS: The demented subjects used more medicines of all kinds (p<0.01), and especially more psychotropics than the nondemented (p<0.001). One in four demented subjects, compared to one in ten nondemented ones used at least two psychotropics (p<0.01). The demented subjects used antipsychotics six times more often than the nondemented ones (p<0.001). Among the nondemented subjects, one out of two antipsychotics users was suffering from depression according to DSM-IV criteria. Three out of four persons who had dementia with Lewy bodies were using psychotropics. Persons with moderate dementia were more commonly using all kinds of psychotropic preparations especially, antipsychotics three times more commonly than persons with mild or severe dementia. CONCLUSION: Psychotropics, especially antipsychotics, are commonly used in the treatment of both nondemented and demented elderly, even without proper indication. Physicians need more training about the appropriate use of psychotropics to minimize their adverse effects.

Kuopio 75+ study: does advanced age predict more common use of psychotropics among the elderly?

The elderly use more psychotropic medication than the general population, and its use has grown during recent decades. The aim of this study was to describe the use of psychotropics in the home-dwelling elderly aged 75 years or older in Finland. This Kuopio 75+ Study is a population-based health survey. A random sample of 700 subjects were drawn from the total population of people aged 75 years or more in January 1998. A geriatrician and a trained nurse carried out clinical examination and interview about the use of medicines for 523 home-dwelling elderly. At least one psychotropic medication was used by 37% of the sample, and 12% were using two or more psychotropics concomitantly. The psychotropic users were older, more often widowed and living alone compared to subjects without psychotropic medication. The probability of psychotropic use increased linearly with age for anxiolytics/hypnotics or antipsychotics, but not for antidepressants. Psychotropics are commonly used in the elderly, particularly among those aged 85 years or more, who are most vulnerable to adverse effects. Careful consideration is needed before prescribing psychotropics to the elderly.

Spouse caregivers' perceptions of influence of dementia on marriage.

OBJECTIVES: To investigate what kind of changes spouse caregivers of demented patients experience after the onset of dementia (a) in the general atmosphere, happiness, and relations of marriage and (b) in the sexual side of marriage. DESIGN: Semistructured telephone interviews of spouse caregivers of demented patients. SETTING: Community-living demented patients and their spouse caregivers in eastern Finland. PARTICIPANTS: The spouse caregivers of 42 demented patients recruited from a previous intervention study. MEASURES: The questionnaire covered different areas of marriage from the time before and after the onset of dementia. RESULTS: A statistically significant decline had occurred in extent of happiness (p = .012), in equal relations (p = .001), and in patients' expressions of sexual needs (p < .001) when compared the time before and after dementia. Twenty-five (60%) of the caregivers reported that the demented patient had shown at least one negative sexual behavioral change during the course of dementia. Seven male patients (24%) had shown the behavioral symptom of constantly expressing need for making love. One in 10 caregivers had experienced positive sexual behavioral changes. In one third of the patients, the expressions of tenderness towards the caregiver had increased. Dementia did not affect significantly the general atmosphere of the marriage. Out of those still in home care, at 3 years from the onset of dementia, 19 couples (46%) continued to practice intercourse, at 5 years the number was 15 couples (41%), and at 7 years it had declined to 7 couples (28%). CONCLUSIONS: Dementing illness has a major negative impact on many dimensions of marriage. However, there are also positive changes and preserved aspects of marriage. Dementia seems to have a surprisingly little impact on whether the couple continues to have intercourse when compared with the general aging population.