1998

Hedda Aguero-Eklund, 1998

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Almberg B. Family caregivers caring for relatives with dementia. Pre- and post-death experu Doctoral dissertation. NEUROTEC, Karolinska Institute, Stockholm; and Stockholm Geront Research Center, Stockholm, Sweden. Correspondence to: Stockholm Gerontology Res Center, Box 6401, S-113 82 Stockholm, Sweden, e-mail: Britt.Almberg@neruotec.ki.se. ISB 628-3846-6.

The purpose of this thesis was to describe caregiving relatives' experiences pre- and post-death relative with dementia disease. This thesis involved 52 caregivers for demented elderly persons 66 non-caregivers for non-demented elderly persons who were included in the Kungsholmen Project, a population-based study of people aged 75 years and over. The Burden Questionnaire (Grafström et al. (1992), the Burnout Measure (Pines et al. 1981), the Patient Hassles (Kinney & Stephens (1991), and the Nursing Home Hassles Scale (Stephens et al. 1991) were in this thesis. The Stress Process Model (Pearlin et al. 1990) was applied in order to present the dif stressors in a caregiver's career. Study 1 There was not always a difference in strain between the caregivers and the non-caregivers. In a cross-gender comparison, females' total experiences proved to be the most strained. ' controlling for gender, the females did not suffer uniformly. Within a same-gender group of caregivers, the results indicate that the males caring for demented elderly persons experienced lack of positive outlook and a limitation of social support. Study 2 In the caregiver group, older wives and daughters were the most likely to report burnout their lives. Limitations in social life, poor health and a lack of positive outlook on caring we most important factors when explaining burnout. Study 3 The caregivers in this study used different coping strategies, depending on whether they felt burned-out or not. Those who experienced burnout used emotion-focused strategies caregivers who did not experience burnout, however, used problem-focused strategies more Furthermore, the caregivers who did not feel burnout used the emotion-focused strategy of acceptance, frequently in combination with the problem-focused strategies of seeking information and seeking social support. The elderly person's living place (home or institution) in this study did not appear to have any significant impact. Study 4 The caregivers in this study who had their demented elderly relatives institution experienced patient hassles (cognitive, behaviour, basic ADL) and nursing home h (caregiver-staff, patient-staff, practical/logistical). The analysis showed the nursing home h to be the stressors explaining variance in burnout. Study 5 Bereaved caregivers who reported more positive appraisal (pre-death) were likely t relieved after the death. They were also satisfied with their support. Caregivers expressed more often when the same person(s) helped them pre- and post-death. Caregivers who reported being exhausted and having a breakdown during the caregiving process expressed negative thoughts and guilt in the post-death phase. Finally, caregivers in the detachment phase who said they were able to say good-bye to their relatives often expressed that they were ready to go on with their lives. KEY WORDS: Dementia, caregiver, non-caregiver, strain, burnout, coping, social support bereavement, grief, gender differences, elderly living place, population-based project.

The clinical diagnosis of Alzheimer's disease (AD) is difficult and an antemortem biological marker serving the function to confirm the presence or absence of the disease would be of great help in the diagnostic procedure. Today, this is possible with biopsies of the brain and with noninvasive methods in a few families with known pathogenic mutations in the amyloid precursor protein gene. In this amino acids, cobalamin, metals and white matter hyperintensities (WMH) were studied in AD subjects as putative biological markers of the disorder.
In study I, reduced levels of plasma taurine and glutamate and cerebrospinal fluid (CSF) glycine, valine in AD patients compared with healthy volunteers were observed. Also low CSF/plasma ratios of alanine, glutamine, glycine, phenylalanine, valine were observed in the AD cases. It is suggested that these changes provide evidence for a disruption of amino acid metabolism that may occur secondary to a disorder of carbohydrate metabolism in AD. Finally, the observed correlations between glutamate and glutamine levels and copying ability and behavioural functions, respectively, would suggest that measurements of these two amino acids may serve as useful early markers for visuo-spatial and behavioural deficits in the disorder.
The plasma levels of aluminium, cadmium, mercury and selenium were increased in study 1 the contents of iron and manganese were lower in the AD sufferers as compared with nondemented individuals. In CSF there were low levels of cadmium and calcium and increased content of copper cases. Calcium in both blood and CSF of AD patients correlated inversely with memory and co^ functions and aluminium in CSF were related with changes in behaviour.
Low CSF levels of cobalamin were observed in AD patients as compared with healthy control subjects in study II. Furthermore, the cobalamin concentrations could not be related to cognition, behaviour or severity of dementia. The volumes of the subarachnoid spaces, ventricles and white matter changes in brain observed on magnetic resonance imaging were not correlated to CSF or serum concentrations of cobalamin.
In study IV, the participants were a population-based cohort of 545 subjects aged over 74 years. The results indicate that serum cobalamin concentrations decrease in normal ageing, but not in A association between AD and low cobalamin levels were found. AD patients had normal cobalamin as compared with aged-matched subjects. The lower cobalamin concentrations observed in AD sufferers still living in their own home seemed to be related to eating habits.
In study V, WMH were assessed with a low field magnetic resonance imager on AD sufferers and subjects with vascular dementia (VaD). The total volume of the WMH as well as the regional distribution of these changes differed significantly between vascular dementia and AD. The regional distribution of the WMH differed between the groups with significantly more changes in the posterior part of the brain as well as in the right hemisphere in the vascular demented as compared with the AD patients. No correlations between cognitive dysfunction and the degree of the WMH were found.
In conclusion, the changes in amino acid concentrations seem to be a secondary phenomenon due to impaired carbohydrate metabolism in the brain, with the exception of glutamate and glutamine which may serve as useful diagnostic markers for visuo-spatial and behavioural deficits in the disease. There are significant changes in metal concentrations in AD sufferers. The relevance of these results are unclear. Cobalamin levels are neither reduced nor related to cognition in AD. Moreover, it is not correlated to brain changes observed on MRI. Low serum cobalamin concentration in AD subjects may be related to eating habits. WMH can contribute to differentiate between AD and VaD, but WMH seem not to be related to the degree of global cognitive decline in dementia and whether they play a causative role in the development of dementia needs to be further investigated.

ISBN 91-628-1019-7.

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The general aims of this thesis were to examine the occurrence of depressive symptoms three years before the diagnoses of depression and Alzheimer's disease (AD), and to study the effects of depression on cognitive functioning in aging and AD. Five empirical studies were conducted. All data were taken from the Kungsholmen Project, a longitudinal population-based study of aging and dementia targeting persons who are 75 years and older, living in the Kungsholmen district in Stockholm, Sweden.
The specific objectives of Study I were to examine preclinical markers of depression, in terms of presence and severity of depressive symptoms, as well as to examine whether cognitive deficits were present during the preclinical period of old age depression. The chief aim of Study II was to investigate depressive symptomatology, with respect to mood- or motivation-related symptoms, in the preclinical phase of AD. In particular, Study II examined mood- and motivation-related symptoms in relation to subjective memory problems to elucidate whether depressive symptoms reflect insight into the dementing process, or is rather a part of the neurodegenerative process. Study HI and IV investigated the influence of depression on AD-related deficits in various cognitive domains (e.g., episodic memory, short-term memory, verbal abilities, visuospatial skill) in mild to moderate stages of AD, whereas Study V examined the influence of depression on global cognitive functioning longitudinally, from the preclinical stage of AD to the time of diagnosis. Study V also addressed whether a concurrent diagnosis of depression causes more rapid decline in global cognitive functioning over a 3-year interval among persons who were going to develop AD.
Findings from Study I showed that depressive symptoms are elevated preclinically in old age depression. Persons who were to be depressed showed a greater number of depressive symptoms (i.e., dysphoria, appetite disturbance) and their symptoms were also more severe (i.e., dysphoria, appetite disturbance, lack of interest, psychomotor disturbances), compared to individuals who remained non-depressed. In addition, depressive symptoms were associated with somewhat poorer global cognitive functioning. These data suggest that there are preclinical markers for old age depression. Study II revealed that depressive symptoms are elevated in preclinical AD as well. There was a predominance of motivation-related (e.g., lack of interest, concentration difficulties, loss of energy) over mood-related (e.g., dysphoria, feelings of guilt, thoughts of death) symptoms. This pattern remained after controlling for subjective memory complaints, indicating that the elevation of depressive symptoms may not merely reflect self-perceived cognitive deficits. Thus, depressive symptoms may be a part of the pathological process of AD. The studies (III and IV) examining the effects of depression on AD-related cognitive deficits showed no impact of depression among mild to moderate cases of AD in episodic memory, verbal ability, and visuospatial skill. However, depression-related deficits in global cognitive functioning were observed in the preclinical phase of AD (Study V), although a diagnosis of depression did not result in greater decline over a 3-year follow-up interval.
To summarize the findings of this thesis, depressive symptoms were found to be elevated preciinically in both depression and AD. However, different patterns of symptoms were present. Mood-related symptoms were more elevated in depression, whereas motivation-related symptoms were dominating in AD. In terms of depression-related effects on cognitive functioning in AD, theresults indicated that, already at a very early clinical stage of AD, the neurodegenerative process overshadows the impact of depression, although this condition is associated with cognitive deficits in normal aging.

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English This thesis deals with different aspects of drug use in a population-based study with participants 75 years and older. The study was performed within the Kungsholmen Project in Stockholm, Sweden, using data from the baseline survey (1987-89), and the first (1991-93) and second (1994-96) follow-ups. In the first two papers we used cross-sectional data (n=1810) to describe the drug use pattern in this population (I), and to examine the association between self-reported symptoms and drug use (II). In the next papers (III-V) a dementia-free cohort (n=1301) was followed up to six years to explore the association between the risk of Alzheimer's disease (AD) and dementia, and the use of aspirin and NSAIDs (III), the use of glucocorticoids (IV), and the use of calcium channel blockers (V). We also examined whether the apolipoprotein E epsilon 4 (apoE e4) allele influenced the effect of these drugs (III-V). The main findings are summarized below. Study I: Sedatives/hypnotics, diuretics, cardiac therapy agents, and minor analgesics and anti-pyretics were the most commonly used drug groups, accounting for more than 40 of the total medicines used. Women used a larger number of drugs than men (3.4 vs 2.6). Anti-thrombotic agents was the only drug group that men used more than women. People living in sheltered accommodation used more medicines than those living in their own homes or nursing homes. Study II: The most commonly reported symptoms were pain and tiredness. Women reported more symptoms than men. Many of the associations between symptoms and drug use reflected established treatments. However, tiredness, loneliness, and depressed mood were associated with use of anxiolytics and hypnotics/sedatives, which might reflect inappropriate treatment. Study III: An increased risk of Alzheimer's disease (AD) was seen among aspirin users that did not carry the apoE e4 allele. A possible protective effect against AD was seen among long-term users of NSAIDs, regardless ofapoE e4 status. Study IV: Use of glucocorticoids was associated with a significantly higher risk of dementia in carriers of the apoE e4 allele (RR 2.39, 95 CI 1.02-5.58). Study V: Use of calcium channel blockers did not protect against AD and dementia, regardless ofapoE e4 status. In summary, women used more medicines and reported more symptoms than men did. Self-reported tiredness, which was associated with use of anxiolytics and sedatives/hypnotics, might reflect too high or too low doses, or an inappropriate choice of drug. Experience of depressed mood was more common among users of sedatives/hypnotics, which could indicate an under-treatment or inappropriate treatment of depression in this population. Up to three-years use of NSAIDs might protect against AD, since no one in this group developed AD three years later. The association between aspirin and an increased risk of developing AD among those with no apoE e4 allele could indicate an alternative mechanism of developing AD in this group. Carriers of the apoE e4 allele that used glucocorticoids showed an increased risk of developing dementia, which suggests a possible vulnerability to gluco-corticoids in this group. Finally, although calcium channel blockers have been found to be neuroprotective in many experimental studies, we could not find a protective effect against dementia in this population. Key-words: drug use, elderly, dementia, Alzheimer's disease, aspirin, NSAIDs, glucocorticoids, calcium channel blockers, apolipoprotein E, population-based study.

ISBN 91-7349-805-X © Christel Cornelius, 2004

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Depression and Dementia in the Elderly Forsell Yvonne, Department of Clinical Neuroscience and Family Medicine, Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Huddinge, Stockholm Gerontology Research Centre, Stockholm, Sweden. Depression and Dementia, both prevalent disorders in an elderly have a complex not fully understood relationship. Depression accompanied by a cognitive dysfunction -"depressive pseudodementia", "dementia syndrome of depression"- as well as dementia accompanied by a depression. Since dementia is a progressive disorder there are also p variation during the natural course.
The studies in this thesis are based on a population of persons aged 75 and over registered in the parish of Kungsholmen, Stockholm, Sweden. Data from physician's examination, nurse interviews, cognitive tests and interviews are used.
In study I demented subjects were divided according to the severity of the disorder using CDR and DSM-III-R staging scales, respectively. between the two staging scales was generally good, with the lowest in the most important group of mild dementia. When MMSE was staging scale the agreement with CDR and DSM-III-R respect moderate.
The variation of psychiatric and behavioural symptoms the course of dementia was analysed in study II, comparing informs physician's examinations and informant interviews. The symptom grouped into clusters using principal components analysis. Little agreement was found between the two sources of information concerning depression. However, there was agreement about an increase in inactivity symptoms as the severity of dementia increased.
The use of DSM-III-R diagnosis Major Depressive Syndrome in versus non-demented subjects was compared in study III. The included in the diagnosis, when analysed in a factor analysis, clustered in a mood and motivation disturbance factor. The motivation factor increased the severity of dementia while the mood factor increased initially and then decreased.
Outcome of depression after three years in non-demented and persons was analysed in study IV. In the non-demented depression while in the demented persons it tended to disappear as the progressed.
The performance of the non-demented depressed on cognitive analysed in study V. Both the encoding and retrieval processes were found to be affected, compared to non-depressed, non-demented persons. The depressed were able to use memory support when it was provided.
The association of age, sex, disability and cognitive dysfunction to the symptoms of Major Depression were analysed in study VI. In a factor analysis the symptoms clustered as a mood and motivational factor. dysfunction affected the two factors similarly as in the previous stud: had a higher score on mood disturbance factor. Age was unrelated to both symptoms. Decreased ADL was associated with an increase both in motivational disturbance factors.
Key words: Depression, Dementia, Elderly population, CDR, CPRS, MADRS, DSM-I

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This thesis concerns the epidemiology of Alzheimer's disease (AD) and some aspects of the validity of such studies.
Three studies on AD etiology have been performed. The first is a case-control study on early-onset AD and a wide range of putative risk factors. The cases were gathered from a clinical study on AD carried out in Italy. The other two etiological studies deal with late-onset AD and are a prevalence study on sociodemographic variables and a case-control study on selected putative risk factors. These two studies to were performed within a population-based study on ageing and dementia that is ongoing in Stockholm, Sweden. The main results are: (1) The prevalence of AD increases with age, even in advanced ages. (2) The prevalence of AD does not vary by gender and education. (3) The main risk factor for both early-and late-onset AD is the familial aggregation of dementia. (4) A second risk factor for early-onset AD may be the advanced age of the mother at index delivery, but this result needs confirmation. No other risk factors reported by others as associated with early-onset AD emerged in our study. (5) High relative risks were found for alcohol consumption and manual work in late-onset AD. Manual work could be an indicator of occupational exposures as well as life conditions or habits. Although both these results may be affected by bias, they are provocative for future research.
Three validation studies were carried out on three different aspects. The first study investigated the reproducibility of AD diagnosis according to the DSM-III-R criteria. A second study concerned the effect of education on the positive predictive value of the Mini-Mental Status Examination (MMSE) used as screening test for dementia in the population survey in Stockholm. The third study compared the information obtained by surrogate informants with the subjects' reports on the putative risk factors studied in the-Italian case-control study. The main results are: (1) The K index of the agreement between different clinicians were 0.54 and 0.58 for the diagnosis of dementia and AD. The agreement on dementia increased to a K value of 0.70 when some modifications were added to the diagnostic criteria. (2) The positive predictive values of the MMSE estimated from a logistic regression model were very similar in the two educational groups (elementary schooling vs high school or university). (3) The non response of the surrogate informants ranged from 0 to 27. The agreement between the subjects and the informants was moderate or better (K index over 0.40) in 73 of the examined possible risk factors.
In conclusion, our results show that the age and familial aggregation are the only certain risk factors for early- and late-onset AD. All the other results suggest interesting working hypotheses for the future rather than definite conclusions. Finally, more attention to the study validity seem necessary, although our results on the diagnostic reproducibility, accuracy of the MMSE, and exposure assessment precision were encouraging.

ISBN: 87-16-15030-9 ISSN: 0065-1427

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Margareta Grafstrom, Department of Clinical Neuroscience and Family Medicine, Section Geriatric Medicine, Karolinska Institute, Stockholm Gerontology Research Center, Stockholm, and Department of Advanced Nursing, Umea University.

The experience of burden in the care of elderly persons with dementia The relatives' experience of burden when caring for a demented elder person and how burden changes over a period of time were investigated. The care receivers were included in a longitudinal population-based study ( ageing (the Ageing and Dementia Project). In the first phase of this study 219 relatives with cognitively impaired and 255 relatives with not cognitively impaired elderly were interviewed. The relatives of the cognitively impaired elderly reported a higher physical and psychological burden and a greater social and affective limitation than the relatives of t non-cognitively impaired elderly (I). The relatives of demented elderly institutions reported similar feelings of burden to those experienced by t home-caring relatives, but the use of psychotropic drugs was lower and the use of somatic drugs and medical facilities was higher in the group relatives with demented elderly in institutions (I). The daughters were mo burdened whether the parent was demented or not. The highest burden w reported when the elderly person was mildly demented. Behaviour problems and moderately decreased ADL functions were strongly associated with burden (II). A group of relatives who spontaneously reported abuse at Tin 1 (III) was followed up two years later (IV). The relatives narrated the relationships toward the demented elderly without expressing abusive reactions. The mutuality in the relatives' previous life together with the demented elderly seemed to be an important factor in the relationship during the progression of the caregiving. In the follow-up interview two years after the first investigation (Time 2), the relatives of demented elder reported less social and affective limitation and less conflicts with others their lives and they judged their physical health to be improved (V). They also reported that some behavioural problems were decreased at Time 2. Key words: Population-based study, Longitudinal study, Family burden Relatives, Dementia, Caregiver, Abuse, Female caregivers, Coping strategies.

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Clinical Aspects of Cognitive Functioning in Aging and Dementia The general purpose of this thesis was to increase our knowledge concerning various clinical aspects of cognitive and memory functioning in old age, with special reference to those problems the clinician may encounter in meeting with the older patient. A variety of specific research issues were addressed ranging factors influencing the prevalence of dementia, whether dementia may be adequately screened using mental status exams, and the relationship between different staging instruments for dementia, through the relationship between memory complaints and cognitive performance, to predictors of cognitive memory performance within demographic (e.g., age, education, gender), psychometric (e.g., performance and verbal IQ), and somatic (e.g., the presence of cardiovascular signs) domains. All six studies f the empirical basis of the thesis were performed using data from the first wave of the Kungsholmen project, which is a population-based, longitudinal study on aging and dementia targeting individuals above 74 years of age. Study I investigated whether self-reported and informant-reported n complaints could reliably predict performance on the Mini-Mental State Examination (MMSE) assesses global cognitive status, in non-demented and demented old adults. Results show. subjects' and informants' reports of memory complaints were moderately correlated. More importantly, the relationship between subjective reports and MMSE score was considerably stronger in the informants' reports compared with subjects' reports. This effect was largely attributable to poor metacognitive judgment on the part of the demented subjects. Another finding of interest w informants' reports of memory deficit was related to subjects' degree of depressed mood. In St we addressed predictors of episodic memory performance in an optimally healthy group of normal old adults. It was found that performance IQ predicted performance across a variety of episodic n tasks (i.e., verbal recall and recognition, spatial recall, activity recall, object recall, face recognition whereas verbal IQ influenced performance on verbal recall only. Women outperformed men in recall, spatial recall, and face recognition, whereas age and education exerted no influence on performance in any task. In Study III, the prevalence rate of dementia and different types of de was determined, according to different age strata, gender, and education. The prevalence rates dementias increased with age: 5.7 in age group 75-79 years, 9.6 in the age group 80-84 years, in the age group 85-89 years, and 32 in the age group 90 years and above. Alzheimer's disease was the most common cause of dementia (54), followed by vascular dementia (24). Less educated people had a higher prevalence of dementia compared with better educated people. This effect, ho was not seen with regard to AD, but was attributable to secondary dementia and, in particular, to de caused by alcohol abuse. No gender differences were observed in this study. In Study IV, we analyzed the accuracy of the MMSE as a screening test for dementia, diagnosed according to the DSM-in-I a cut-off point of 23/24 on the MMSE, the sensitivity was 87, the specificity 92, and the p predictive value 68. Age and education had no effect on specificity, and a slight effect on spec The false positives accounted for 10 of those who screened positively, the main causes being pi and psychiatric diseases. As expected, sensitivity decreased as MMSE cut-off score decreased, whereas the opposite pattern was found for specificity and positive predictive value. Study V address relationship between DSM-III-R and CDR as staging instruments for dementia, as well relationship between these two instruments and the MMSE (both as a continuous measure of cognitive status and as a staging instrument). Including the entire range of severity of dementia, the agreement between DSM-III-R and CDR was good. The agreement between these two scales were excellent in moderate to severe stages of the disease and moderate in the early stages. Both these scales showed high correlations with total MMSE score, although the relationships were considerably weaker when the MMSE was trichotomized as a staging instrument. Study VI sought to determine the relationship between cardiovascular signs (e.g., cardiac murmur, cardiac arrhythmias, murmur of carotis) and cognitive status (i.e., MMSE score) as well as episodic memory performance (i.e., word recall) in a group of non-demented adults. Results indicated that a composite measure of cardiovascular signs was negatively related to both MMSE and word recall, after controlling for the effects of age, education and cardiovascular drug intake. By contrast, there was no relationship between blood pressure a cognitive variables. In general, this work provides a rich source of information of potential value for geriatric practice. Specifically, the results have implications with regard to a variety of issues re] the assessment of cognitive status in the older patient, including the importance of (a) employing sensitive measures in detecting and staging dementia diseases; (b) taking into account multiple demographic (e.g., age, gender, education), psychometric (e.g., performance IQ), and somatic (e.g., cardiovascular signs) individual-difference variables; and (c) considering carefully informants'' of the patient's cognitive functioning.

© Michaela Grut, 1995

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Blood Pressure and Dementia in the Very Old. An epidemiologic study There is a considerable public health interest in the vascular causes of den because they are potentially treatable and preventable. A number of vascular ft may be associated with dementia. Hypertension is supposed to be the most powerful vascular risk factor for dementia because of its contribution to cerebrovascular disease. However, there have only been a few population-based studies about the direct relationship between blood pressure (BP) and dementia.
We used the baseline and first follow-up data from the Kungsholmen Project to examine the relationship between BP and dementia. The project is a longitudinal study on aging and dementia, including all inhabitants of the Kungsholmen district in Stockholm aged 75 years and older on October 1, 1987. Of the eligible subjects, (77) participated in the initial survey (baseline) in which the Mini-Mental Examination (MMSE) was used as a screening test for dementia. The Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised diagnostic criteria were used to define dementia. During 1992-94, the following groups received thorough clinical examinations: 1) the initial cohort, 2) all inhabitants of the Kungsholmen district who were born in 1915, and 3) all residents of the St ( district who were born in 1902 and before.
There was a cross-sectional relationship between relatively low BP (systolic < 140 or diastolic <75 mm Hg) and dementia or cognitive impairment (MMSE In other words, the prevalence of dementia or cognitive impairment was high in subjects with relatively low BP. The correlation between low BP and cog impairment partially accounted for the increased mortality associated with lo1 (systolic <130 or diastolic <75 mm Hg).
Longitudinal BP reduction (decrease more than 5 mm Hg from baseline to follow up) was related to increased incidence of dementia, which may explain the < sectional association between relatively low BP and dementia. We suggest: 1) BP reduction is an early pathophysiological change in a dementia process, particularly Alzheimer's disease; 2) clinically unrecognized vascular lesions in the brain or atherosclerosis are responsible for both dementia and BP reduction.
In addition, baseline systolic BP >180 mm Hg was related to an increased risk of developing dementia (relative risk 1.6, 95 confidence interval 1.1-2.6) compared to systolic BP of 141-160 mm Hg. The association was not explained by age or gender but was somewhat reduced when all covariables including stroke were included in the model.


© Zhenchao Guo, 1998

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Hassing, L. (1998). Episodic memory functioning in nonagenarians: Effects of demographic factors, vitamin status, depression, and dementia. Department of Psychology, Goteborg University, Box 500, SE-405 30, Goteborg, Sweden. E-mail: Linda.Hassing@psy.gu.se

When old people complain about failing memory they are typically referring to a decline in episodic memory. Episodic memory enables conscious recollection of personal events and episodes from one's personal past. It involves information that is tied to a specific time and place, like, for example, whether or not I took my medicine this morning. This thesis is concerned with how different conditions influence episodic memory functioning in the 10th decade of life. In four studies, episodic memory functioning among nonagenarians was examined in relation to demographic characteristics, vitamin status, dementia, and depression. The studies emanate from the Kungsholmen project, a longitudinal population-based study carried out in Stockholm, Sweden, and are based on samples of people aged 90 years and older. The purpose of Study I was to assess the relative importance of age, gender, and education in episodic memory functioning. In Study II-IV the aim was to investigate how episodic memory functioning is affected by different conditions frequently seen in very old age. Thus, in Study II the focus was on potential effects of low levels of vitamin Bi; and folic acid on episodic memory functioning. In Study III, the primary aim was to examine whether major depression (MD) adds to the episodic memory deficit that accompanies Alzheimer's disease (AD), and a second aim was to assess the effects of MD on episodic memory performance in nondemented nonagenarians. And finally, in Study IV, the research question was whether the episodic memory deficits seen in dementia differ in AD and vascular dementia (VaD). The following tasks were used to assess episodic memory performance: face recognition, word recognition, immediate and delayed free recall of words, and object recall with selective reminding. To assess global cognitive functioning, the Mini-Mental State Examination (MMSE) was used.
The results from Study I showed that, in a sample of healthy very old individuals, age, gender, and years of formal education accounted for only 3-8 of the variation in episodic memory performance. This is a low figure when compared to findings from studies based on adults in their 70s and 80s. This may reflect selective survival effects in the study sample, reducing the impact of demographic factors on memory performance. In Study II-IV, it was found that primary memory is unaffected by low vitamin status, depression, and dementia. Further, the results of Study II showed no effects of vitamin B12 level in any of the memory tasks nor any interaction effects between vitamin B12 and folic acid. Negative effects of low levels of folic acid were found in both immediate and delayed word recall as well as in object recall, but no such effects were found in the recognition tasks. These results indicate that folic acid may be more critical than B12 to memory functioning in late life. In Study III, no effects of depression on episodic memory performance were found in the sample of nondemented individuals. Further, it was found that depression in AD did not add to the episodic memory deficits already seen in this disease. The findings of no effect of MD on episodic memory is interpreted such that those symptoms of MD that are most likely to affect memory functioning (e.g., lack of effort, loss of energy, concentration difficulties) may be common in AD as well as in non-depressed very old people. In Study IV, no performance differences were observed between patients with AD and VaD in face recognition and object recall, although patients with AD performed at a lower level than those with VaD in word recall. The selective AD-related deficit in word recall is interpreted in terms of greater impairments of various language-related skills in AD compared with VaD. Taken together, the findings from this thesis are mostly in accordance with findings from studies based on younger cohorts, with the exception of MD having no effect on episodic memory performance in very old age. Thus, the findings of episodic memory deficits along with intact primary memory functioning in folate deficiency and dementia, extend previous research to individuals in the 10th decade of life.
Key words: Episodic memory, secondary memory, primary memory, nonagenarians, demographic factors, vitamin B];, folic acid, Alzheimer's disease, vascular dementia, major depression.

ISBN 91-628-3215-8

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" Well-being Among the Very Old. A Survey on a Sample Aged 90 Years and Above "
Correspondence Address: pernilla.hilleras@neurotec.ki.se This thesis examines well-being among the very old and the factors believed to influence the three components of well-being called life satisfaction, positive affect and negative affect. It also examines activity patterns, the factors related to activity and the consequences of different types of activity for well-being. The study is part of the Kungsholmen project which involved all inhabitants aged 75 years and over, living in a specific part of the inner city of Stockholm. This thesis covers 105 subjects who were 90 years and older, scoring 24 points or above on the Mini-Mental State Examination. Well-being was assessed with the Positive and Negative Affect Schedule, the Life Satisfaction Index-B and the Life Satisfaction Index-Z.
Study I examined life satisfaction among the very old and the factors believed to influence life satisfaction. Life satisfaction was slightly lower than in other studies, which involved samples of younger elderly. In addition, factors such as life events, activities, personality and social contacts were assessed in order to determine their relative influence on life satisfaction. The very elderly tended to have higher life satisfaction if they had an extraverted and emotionally stable personality, excellent subjective health, good social relationships, and if they did pleasurable activities. The factors associated with life satisfaction were also investigated qualitatively. With this approach we found out what the elderly themselves believe gives them life satisfaction. The quantitative and qualitative data came up with some factors in common (e.g., health, family contacts), but there were some differences as well.
Study II examined Positive Affect and Negative Affect among the very old and the factors, which might influence these. Results showed that Positive Affect and Negative Affect were virtually uncorrelated. Comparing the results with studies of younger age groups. Positive Affect appears to decrease with age, while Negative Affect shows no clear age trend. The very elderly tended to have higher Positive Affect during the past year if they had excellent health, an extraverted personality, a definite religious or non religious belief, lived with another person, had good social relationships, read a lot, were well educated and followed radio/TV news. They seemed to have higher Negative Affect during the past year if they scored high on neuroticism, had many adverse life events, did not read, and did not participate in group activities.
Study III examined activity patterns among the very old, the factors related to activity and the consequences for well-being. Activities over the previous day were rated for degree of intellectual, social and physical activity. This age group tended to have variable but relatively low activity levels over the day. Good health and not moving house were associated with greater intellectual activity. Extraversion and negative life events (such as death of close friend or family member) were associated with greater social activity, while younger age and better health were associated with greater physical activity. There was also a positive association between physical activity and well-being.
Study IV examined whether there is an association between objective health, measured as clinical medical diagnoses, and well-being among the very old. Subjects were given a medical examination covering eye diseases, osteoarticular diseases, cancer, cerebrovascular diseases, bronchopulmonary diseases, heart diseases, and endocrine diseases. The data suggested there is no association of physical diagnoses with well-being, despite the fact that a self-rated health measure was found to be associated with life-satisfaction.
Study V focused on the subjective experience of extreme old age for people scoring high and low respectively on well-being measures. The purpose was to illustrate and expand upon the quantitatively derived findings from previous studies using a qualitative approach inspired by Grounded Theory. The results suggested that 'outlook on life', 'social and emotional ties', 'engagement with the outside world' and 'physical capability' are important contributors to subjectively experienced well-being in this age group.
In these studies, personality emerged as the major determinant of well-being. In addition, the results showed that this age group has a low activity level which is affected by factors suet as health, personality and life events.

Pernilla Hillerås,2000

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Very old persons' experiences of ageing The overall aim of the thesis was to understand elderly people's lived experiences of ageing and their life situation in very old age. The participating persons t been involved in and followed through all studies in the thesis. In study I some characteristics of quality of life in old age were illustrated by means of empirical data and Allardt's definition of the concept. To the elderly people investigated quality of life meant contentment and a peaceful life, independence and health resource for this, personal integrity in terms of moral quality and a caring attitude. A phenomenological hermeneutic approach was utilised in the subsequent studies. In study II 30 of the participants were followed up and interviewed in depth a1 their lived experiences related to quality of life in old age. Different patterns of in old age appeared depending on the meaning that the participants ascribed to t experiences of quality of life: successful ageing, good old age, a comparatively good life in old age, bad ageing and a miserable life in old age. Data for studies V was collected in the form of thematic life story interviews with 15 participants. Study III illuminated eight participants' experiences of feeling old in advanced The understanding was that the very old persons who also felt old were in a pi of transition. The distinguishing qualities of those that felt old were also found to be in line with the dystonic dominance in the ninth stage designated by J Erikson and added to the previously described life cycle. Study IV aimed at identifying and revealing the meaning of central themes in very old people's stories. The results showed that the interviewees by means of the central life the communicated personal and functional meanings that were understood influencing very old persons' experience of their everyday life in a positive way. Study V highlighted the very old persons' view of their future from the perspective of philosophy of life. The participants were found to view their future in ways ranged from a tangible positive approach via a wait-and-see policy to a negative approach. Positive approaches were related to hope and feelings of purpose meaning. The comprehensive understanding of the thesis was that the challenge in very age will be to live a life as good as possible notwithstanding changes in health in environment. In the process of ageing positive tendencies in balancing developmental crises as described by EH Erikson will contribute to pos experiences of life. KEY WORDS: very old people, lived experience, quality of life, transitions in age, philosophy of life, life stories, phenomenological hermeneutics, EH Eriksson theory

Margareta Nilsson, 2000. ISBN 91-628-4448-2

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This doctoral thesis investigates early predictors of Alzheimer's disease (AD) and dementia in the general population, and verifies the accuracy of different syndromes of cognitive impairment for predicting progression to dementia in a dementia-free cohort of 1435 persons aged 75-95 from the Kungsholmen Project, Stockholm, Sweden. Persons were reexamined after 3 and 6 years to detect incident cases of dementia and AD (DSM-III-R criteria).
In Study I, the evolution of persons with Cognitive Impairment, No Dementia (CIND) was explored. CIND was defined as scoring 1 standard deviation below age- and education- specific norms on a test of global cognitive functioning. The evolution was heterogeneous; similar proportions of persons with CIND died, progressed to dementia, and remained stable or improved. Subjects with CIND had a 3-fold increased risk of progressing to dementia over 3 years compared to cognitively intact elderly, and a 2-fold increased risk of death. Individuals who improved at 1st follow-up did not have a significantly higher risk of later progressing to dementia than persons who had never been impaired.
In Study II, persons with CIND were more likely to have an anxiety disorder and symptoms of suspiciousness than cognitively intact elderly.
In Study III, a simple 3-step procedure, analogous to clinical practice, was evaluated to detect persons who would develop dementia after 3 years. A high positive predictive value was found; between 88-100 of persons with memory complaints (step 1), global cognitive impairment (step 2), and deficits in episodic memory or verbal fluency (step 3) progressed to dementia over 3 years. However, the sensitivity of the procedure was poor, as only 18 of persons in the preclinical stage of dementia exhibited impairment on all 3 measures.
In Study IV, the occurrence and predictivity for dementia of 7 syndromes of cognitive impairment were examined, including previously proposed criteria for Mild Cognitive Impairment (MCI) subtypes, and modified versions, which relaxed the criterion for normal general cognitive functioning. MCl-amnestic was the least common MCI type, and MCI-single-nonmemory was the most frequent. Modified criteria increased the occurrence of all MCI subtypes and increased predictivity of MCl-amnestic for future AD. Persons with MCI-multidomains and MCl-amnestic had significantly increased relative risks for future AD. Original and modified criteria for MCI subtypes were not able to identify 3.6 of the population who only have global cognitive deficits, but have a 16-fold risk for AD. In Study V, the presence of neuropsychiatric symptoms in persons with different subtypes of MCI was examined, and their contribution to the prediction of AD was evaluated. Compared to cognitive intact elderly, elevated neuropsychiatric symptoms were found in persons with MCl-amnestic and MCI-multidomains. Motivation-related depressive symptoms were associated with a nondegenerative outcome in persons with MCI-multidomains. Anxiety symptoms were predictive of 3-year progression to AD in persons with MCl-amnestic or MCI-multidomains. In persons with no detectable cognitive deficits, mood-related depressive symptoms predicted impending AD. In summary, at the population level, cognitive impairment in nondemented elderly is a heterogeneous condition, dementia being one of 3 main outcomes. A 3-step procedure that simulates routine clinical practice can identify with high predictivity those persons who will progress to dementia, but the sensitivity of this procedure is low, as less than one fifth of future dementia cases can be identified. Previously proposed criteria for MCI can detect only half of the persons with cognitive deficits in the general population, but subtypes of MCl-amnestic and MCI-multidomains have high predictive power for identifying persons who will develop AD. A simple modification of the criteria increases the occurrence without diminishing the predictivity. Furthermore, psychiatric evaluation of persons with MCI can help to better identify a neurodegenerative progression in syndromes of cognitive impairment.
Key words: mild cognitive impairment, Alzheimer's disease, dementia, epidemiology, population-based study, aging, cognition, geriatrics, neuropsychology

ISBN: 91-7140-055-9 © Katie Palmer

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The aim of this thesis was to find occurrence of drug side effects in the elderly by studying the association between changes in clinical parameters and prevalence of self-reported symptoms and the use of drugs in an elderly population.
The studies were performed in the Kungsholmen project, a longitudinal population based study of aging and dementia in Stockholm. Data from baseline (1987-89), 151 follow-up (1991-93), 2’ follow-up (1994-96), and 3rd follow-up (1997-98) were used. The first two articles describe cross-sectional studies examining the prevalence of low blood pressure (Paper 1) and sodium and potassium disturbances (Paper II) with respect to medication (baseline, n=1748 and 1558). The third paper examined the association between drug use and hyperglycemia, as measured by increased HbAlc levels (2’ follow-up, n578). The fourth article is a longitudinal (6 years follow-up) study of age-related impairment of renal function in connection to drug use (baseline to 3rd follow-up, n=242). The fifth article examines the use of antidepressants and anxiolytics in relation to self reported somatic and psychiatric symptoms (3” follow-up, n=419). The most important results are summarized below.
Study 1: The use of potassium-sparing diuretics, dopaminergic antiparkinsonian drugs and neuroleptics were significantly associated with low systolic blood pressure and dopaminergic antiparkinsonian drugs with low diastolic blood pressure.
Study II: The occurrence of hyponatraemia was associated with the use of carbamazepine, laxatives (enema), diuretics and ACE-inhibitors and hypernatraemia with osmotically active laxatives. Hypokalaemia was associated with thiazide-related and combination diuretics and hyperkalaemia with potassium-sparing diuretics, 3-blockers, cytostatic drugs and tricyclic antidepressants.
Study III: Use of bop diuretics was significantly associated with high HbAlc levels in both women and men. Eighteen percent of users had high levels compared with 8% in non-users.
Study IV: The prevalence of renal impairment, defined as estimated creatinine clearance (CE) <50 mi/min, was 33 % at baseline and 93 % in 3’’ follow-up. The use of drugs that should be avoided or be prescribed in reduced doses in mild or moderate renal insufficiency increased over time, with few exceptions. Doses decreased for digoxin, spironolactone and allopurinol, but increased for drugs against peptic ulcer, ACE-inhibitors and citalopram.
Study V: Elderly treated with antidepressants showed a high total score on the Comprehensive Psychopathological Rating Scale (CPRS) (23.6±10.9) and score for depressive symptoms (6.4±7.2). The scores were even higher for users of anxiolytics (26.3±23.2 and 7.6±14.4). The use of antidepressants was significantly associated with several somatic symptoms such as vertigo/dizziness, tendency to fall, involuntary urination, and shortness of breath. The use of anxiolytic drugs was associated with vertigo/dizziness and shortness of breath.
Conclusions: Side effects of drugs occur frequently in an elderly population and with many drugs that are generally not considered in clinical practice.
There is a continuous age-related loss of renal function. However, apparently physicians often do not adjust the treatment according to this very important age-related physiological change, which in turn increases the risk of side effects.
Our results also indicate ineffective and inappropriate treatment of depression as well as side effects of anxiolytic and antidepressant therapy in the elderly.
Keywords: Drug utilisation, elderly, side effects, adverse drug reactions, hypotension, hyponatremia, hypernatremia, hypokalaemia, hyperkalaemia, hyperglycemia, renal
insufficiency, self-reported symptoms, antidepressants, anxiolytics

ISBN: 91-7140-365-5 © Galina Passare

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This doctoral thesis concerns a community-based, prospective study aimed at investigating the complex relationship between blood pressure (BP) and risk of dementia in a dementia-free cohort (n = 1301) aged >75 years in Stockholm, Sweden. After baseline survey (1987-1989). the cohort was followed for over 6 years, during which 2 waves of clinical examinations (1991-1993 & 1994-1996) for dementia and Alzheimer's disease (AD) {DSM-III-R diagnostic criteria) were performed. Data were analyzed with Cox proportional hazards models. The major findings from the five research papers included in this thesis are summarized below.
In Study I. the relationship between BP and dementia was examined. Subjects with high systolic BP (>180 vs. 141-180 mm Hg) or low diastolic BP ($65 vs. 66-90 mm Hg) had an increased risk for AD and dementia. The association between low diastolic BP and high risk of dementia was particularly pronounced among the users of antihypertensive drugs. Systolic BP <140 mm Hg and diastolic BP >90 nun Hg were not associated with the risk of AD and dementia.
In Study II. we examined the relationship between pulse pressure and risk of dementia and AD. Compared with median tertile of pulse pressure (70-84 mm Hg), lower pulse pressure (<70 mm Hg) and higher pulse pressure (>85 mm Hg) were both found to be significantly associated with an increased risk of AD and dementia. The U-shaped relationship between pulse pressure and risk of dementia was present mainly among women.
In Study III. the combined effects ofAPOE e4 allele, high systolic BP. low diastolic BP, and use of antihypertensive drugs on the risk of AD were assessed. APOE e4 in combination with either high systolic BP (^140 mm Hg) or low diastolic BP (<70 mm Hg) greatly increased the risk of AD. Antihypertensive drug use significantly reduced AD risk regardless of APOE e4 status, and counteracted the combined risk effect of APOE e4 allele with high systolic BP on the risk of AD.
In Study IV. we found that systolic and diastolic levels greatly decreased over 3 years before a dementia diagnosis and continued to decline thereafter. Diastolic BP decline was not significantly predictive of dementia, whereas a greater decline in systolic BP (>15 mm Hg vs. no decline) was statistically associated with an elevated risk for AD and dementia among persons with systolie pressure level <160 mm Hg or those with vascular disease at baseline.
Finally, Study V indicated that heart failure was associated with relative risks of 1.7 (95 CI, 1.2-2.4) for AD and 1.5 (95 CI. 1.1-2.0) for dementia. Use of antihypertensive medications counteracted the risk effect of heart failure on AD and dementia. Heart failure and low diastolic BP (<70 mm Hg) showed an additive effect on the risk of AD and dementia.
In summary, low diastolic and high systolic pressure, and both low and high pulse pressure are determinants of AD and dementia in very old adults. BP levels were affected by the dementing process. Chronic heart failure may increase the risk of dementia. Use of antihypertensive drugs reduces the risk of AD and dementia, diminishes the risk effects exerted by APOE e4 allele and heart failure on AD and dementia, and modifies the joint effects of high systolic BP and the APOE e4 allele on the risk of AD. These findings indicate that the atherosclerotic process and cerebral hypoperfusion may be involved in the pathogenesis and clinical expression of AD and dementia. Key words: blood pressure; heart failure; dementia; Alzheimer 's disease; apolipoprotein E gene; antihypertensive medication; aging; geriatrics; epidemiology; population-based study

ISBN 91-7349-75 5-X © Chengxuan Qiu 2003

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Robins Wahlin, T-B (1999). Cognitive Functioning in Late Senescence; Influences of Age and Health. Doc Dissertation, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Division of Geriatric Medicine, Karolinska Institute; and Stockholm Gerontology Research Center, Section of Psychology. Correspondence: Stockholm Gerontology Research Center, Box 6401, S-11 Stockholm, Sweden, e-mail: Tarja-Brita.Robins.Wahlin@neurotec.ki.se 1999; ISBN 91-628-3861-X.

The overall aim of this doctoral thesis was to investigate potential age-related differences between groups of healthy very old adults from 75 to 96 years of age in various cognitive functions. An additional objective was to examine the influence of individual-difference variables within demographic ( education, gender), psychometric (e.g., general cognitive status; MMSE) and biological (e.g., vita BIZ, folic acid [FA]) domains on cognitive functioning in late life. The studies were conducted within the realm of the Kungsholmen Project, which is a community-based, longitudinal study of persons aged 75 years and above, living in the parish of Kungsholmen, Stockholm. Participants were care! screened for health, using a variety or exclusion criteria (e.g., dementia, sensory loss, psychiatric disc Study I and II examined the influence of age on visuospatial ability, spatial orientation, percept motor speed and accuracy, and motor functions of the hands. Results indicated an age-related deterioration in visuospatial abilities, spatial orientation and perceptual-motor speed. There were age-related differences in the tests of hand-motor functioning and perceptual-motor accuracy. Visuospatial performance was higher under self-paced than under paced conditions across the entire age range. Further, results suggested that the abilities underlying time recognition may deteriorate later in normal aging process than those underlying time drawing. Individual-difference analyses indicated t in addition to age, visuospatial functioning and spatial orientation were related to MMSE and education in Study I. In Study II, visuospatial functioning and thyroid stimulating hormone (TSH) were I related to perceptual-motor speed. Study III and IV investigated the effects of low levels of the vitaminB12 (Bi2<200pmol/L) and Folic Acid (FA<11 nmol/L), and the influence of levels of thyroxine (T4) and TSH within normal ranges on cognitive performance, respectively. Tasks assessing visuospatial ability, spatial orientation, perceptual-motor speed, short-term memory, verbal fluency, and episodic memory were examined. There were differential vitamin-related effects, such that subjects with vitamin levels showed deficits in visuospatial abilities, perceptual speed, short-term memory, and low fluency, but not in the remaining tests. In general, the effects of FA exceeded those of BIZ. T4 unrelated to cognitive performance although TSH was positively related to episodic memory performance but not to the remaining tasks. Those effects were independent of age, level of education, and depressive mood symptoms. Finally, Study V examined the degree to which demographic variables and an ii of performance IQ can predict episodic memory performance in a longitudinal study targeting optimally healthy very old adults. Subjects were assessed at baseline (Tl) and after one (T2) and (T3) years. There was a modest, but reliable, improvement of both verbal and nonverbal men performances from T1 to T2, followed by stability from T2 to T3. No predictor variable was related to rate of change from T1 to T2, although PIQ influenced rate of change in verbal memory from T2 to T3. This effect resulted from performance gains among high PIQ. subjects and performance decline among low PIQ subjects. The results suggest mat changes in episodic memory in very old age may necessarily be characterized by decline. Specifically, healthy older adults may show stability and, in s instances, display practice-related gains in verbal and nonverbal episodic memory. The potential for performance gains over time may be greatest for the most cognitively able individuals. Taken together the studies indicated that the well-known age-related deficits in visuospatial abilities, spatial oriental and perceptual-motor speed continue into very old age. However, episodic memory may not necessarily decline if practice opportunities are available. In addition to age, low levels of vitamin Bi2, and FA ^ related to deficient performance in cognitive tasks in which fast and accurate processing of n information is required, but not when pre-existing knowledge structures may be utilized. TSH positively related to episodic memory performance, which was interpreted in terms of its potential effects on encoding and consolidation processes in episodic memory. At a general level, then, research underscores the importance of various health-related variables in characterizing late cognitive functioning. Key words: cognitive functioning, aging, health, individual differences.

Tarja-Brita Robins Wahlin

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This thesis investigated the use of drugs in a population of very old persons. The patterns of use, particularly of psychotropic drugs, and its appropriateness were assessed. Drug use was also assessed according to dementia diagnosis and in relation to the presence of psychiatric illnesses. Inasmuch as there is extensive literature on drug use in older persons, data on the very old is scant. The Kungsholmen project, a longitudinal population-based study on aging, provided us with the opportunity to examine the use of drugs in this group of older persons.
There was a high rate of the use of drugs, in general, and psychotropic drugs, in particular, in this very old population. Drug use was more among women and in institutions. The most commonly used were drugs for the cardiovascular system, nervous system, and alimentary tract and metabolism. There was an increase in the use of drugs for the most common diseases affecting the older population.
More persons with dementia used psychotropic drugs, particularly antipsychotics. Persons without dementia, on the other hand, more commonly used hypnotics-sedatives. Questionable prescribing was evident in the use of multiple psychotropic drugs and high level of long-acting BZD use. There was underdiagnosis and undertreatment as shown in the low level of antidepressants used. Careful prescribing was noted in the use of SSRI, the transition to use short-acting BZD, and the generally lower doses taken.
There was widespread exposure to potentially inappropriate drug use. The exposure to inappropriate use reflected the frequency with which drugs were prescribed. Persons with dementia were more commonly exposed to potential DDI and drug-disease interactions, drug duplication, anticholinergic drugs involving psychotropic drugs. Psychotropic drugs, in turn, were the most commonly used drugs in this group. Persons without dementia were more commonly exposed to potential DDI and drug-disease interactions involving cardiovascular drugs, which were the most commonly used in this group of subjects.
Sleep problems were found to be common in this population, particularly women. Poor self-rated health, depression, pain, and one or more chronic diseases were related to sleep problems. The use of hypnotics-sedatives, other psychotropic drugs, and nonpsychotropic drugs were also related to sleep problems. Hypnotics-sedatives appeared to be prescribed for the management of the sleep problem and not the underlying cause: more persons found to have sleep problem and depression used hypnotics-sedatives than antidepressants.
Hypnotics-sedatives were commonly used for sleep problems, depression, and anxiety in persons with dementia and anxiolytics were used for psychosis. The heterogeneous nature of a behavioral disturbance was seen in the manner with which drugs were used relative to the presence of a particular BPSD. This was evident in the different types of psychotropic drugs used for a particular BPSD. There was an increase in the proportion and type of psychotropic drugs used with increasing severity of dementia.

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This thesis explored the impact of different lifestyles in late life on the occurrence of Alzheimer's disease (AD) or dementia. Smoking, vitamin 812 and folate in relation t( have been extensively studied, but the results are inconsistent. Research concerning the association between dementia and social network or social activities is scarce. All studies for this thesis were done using data from the Kungsholmen Project, a longitudinal population-based study on aging and degenerative disorders in Stockholm. The population for this Project consisted of all those subjects who were 75 years and older on October 1, 1987, and registered in the Kungsholmen district of Stockholm, Sweden. The prevalence of AD and dementia was negatively associated with smoking (adjusted odds ratios = 0.6, 95 confidence interval (CI) == 0.4-1.1 and 0.4-1.0). In contrast, hazard ratios (HR) and (95 CI) of incident AD and dementia in relation to smoking 1.1 (0.5-2.4) and 1.4 (0.8-2.7). Mortality over a 5-year follow-up was greater among smokers in demented (HR = 3.4) than nondemented subjects (HR = 0.8). Compared with subjects having normal serum levels of both vitamin 812 and f< subjects with low levels of vitamin 812 (<. 150 pmol/L) or folate (<10 nmol/L) t higher risk of developing AD (RR = 2.1, 95 CI = 1.2-3.5). The association was stronger (RR = 3.1, 95 CI = 1.1-8.4) in subjects with good baseline cognition (MM 26). A comparable pattern was detected when low vitamin levels were defined as vitamin B12 < 250 pmol/L and folate < 12 nmol/L. An extensive or moderate social network decreased the risk of dementia by 30 (95 = 0.47-0.97) over a 3-year period. Daily to weekly engagement in mental, social, or productive activity was inversely related to dementia incidence. Adjusted RRs (95 were 0.54 (0.34-0.87) for mental activities, 0.58 (0.37-0.91) for social activities and (0.38-0.91) for productive activities. An active and socially integrated lifestyle, decreased the risk of having an extensive/moderate social network, and high level of participation in social/leisure activities and associations, was related to a lower dementia risk. Compared with the lowest level of activity and integration, the adjusted RR was 0.56 (95 0.35-0.89) for low level of activity and integration, 0.34 (0.20-0.59) for high levels of activity and integration, and 0.29 (0.11-0.78) for the highest level of activity integration. The conclusions of this thesis are: smoking is not protective for AD or dementia cross-sectional association might be due to differential survival. Low levels of s vitamin 812 and folate may be involved in the development of AD. A clear association was detected when both vitamins were taken into account, especially among cognitively intact subjects. An active and socially integrated lifestyle such as having < social network, frequent participation in stimulating activities, whether physical-, so or mental-oriented, might prevent an elderly person from developing dement postpone the onset of the disease. Key words: Alzheimer's disease, dementia, elderly, emotional support, folate, incidence, integration, intellectual activity, lifestyle, mental activity, physical activity, prevalence, productive activity, smoking, social activity, social network, risk factor, and vitamin E.

© Hui-Xin Wang 2001
IS8N91-628-4783-X

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