| 1. |
- Johansson, Annica, 1969, et al.
(författare)
-
Homocysteine levels in patients with Alzheimer's disease are influenced by the glutathione s-transferase omega-1 (GSTO1) gene
- 2005
-
Ingår i: Haematologica Reports. - 1824-9337. ; 2005:1(3):June
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: A substantial body of literature confirms an association between elevated blood levels of homocysteine and cognitive dysfunction, including Alzheimer’s disease (AD). Oxidative stress is a risk factor for AD. Elevated homocysteine levels might partially reflect redox status; its remethylation to methionine is coordinated by the redox-sensitive enzyme methionine synthase. Glutathione S-transferase omega-1 (GSTO1) is protective against oxidative stress, and the polymorphism Ala140Asp modifies the age-of-onset of AD. Aim: To investigate whether the GSTO1 Ala140Asp polymorphism is related to homocysteine levels in AD patients. Methods: Plasma homocysteine levels and the GSTO1 polymorphism Ala140Asp were analysed in 244 consecutive patients with clinically diagnosed AD. Results: Homocysteine levels differed significantly between the three genotypes (p=0.002) analysis of variance, Durbin-Watson D Statistic. The levels were 11.8±3.6 µmol/L in patients with the Ala/Ala genotype (n=118), 13.5±5.0 µmol/L in the Ala/Asp group (n=105), and 14.1±6.0 µmol/L in patients with the Asp/Asp genotype (n=21). Carriers of at least one Asp allele showed significantly higher plasma homocysteine levels compared to non-carriers (p=0.002) two-sample t-test. Conclusion: The association between homocysteine levels and this GSTO1 polymorphism supports the suggestion that increased homocysteine in AD patients may be a consequence of oxidative stress.
|
|
| 2. |
- Wattmo, Carina, et al.
(författare)
-
Cholinesterase inhibitor therapy does not affect time spent in nursing homes in patients with Alzheimer’s disease.
- 2016
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: The time spent in nursing homes (NHs) by patients with Alzheimer’s disease (AD) might be influenced by many factors, e.g., sociodemographic and clinical characteristics, rate of disease progression, and concomitant disorders. Whether different aspects of cholinesterase inhibitor (ChEI) therapy (drug agent, dose, and duration) affect time spent in NHs has not been investigated. We studied the relationship between these potential predictors and time spent in NHs. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for the long-term assessment of ChEI therapy in a routine clinical setting. This presentation includes 220 deceased SATS participants clinically diagnosed with mild-to-moderate AD (Mini-Mental State Examination score, 10–26 at the start of ChEI treatment) who were admitted to NHs during the study. Cognitive and activities of daily living (ADL) capacities were evaluated at the baseline and semiannually over 3 years. The dates of nursing home placement (NHP) and death were recorded. Variables that determined time spent in NHs were analyzed using general linear models. Results: The mean (95% confidence interval) time spent in NHs was 4.06 (3.69–4.43) years: 2.78 (2.19–3.38) years for men vs 4.53 (4.09–4.96) years for women; P < 0.001. When considering the interaction effect of sex and living status, males living with a family member spent a shorter time in NHs (2.15 (1.48–2.83) years) vs the other groups: females living with family, 4.75 (4.00–5.50) years; males living alone, 4.00 (2.96–5.05) years; and females living alone, 4.41 (3.87–4.95) years; P < 0.001. The multivariate model showed that a shorter stay in NHs was independently related to being a man living with family, lower basic ADL at NHP, and more concomitant medications. Age, cognitive or instrumental ADL capacities at NHP, rates of decline in cognition or function, and ChEI type, dose, and treatment duration were not significant predictors. Conclusions: Women cared for their spouses with AD at home longer than did men. The situation of these female informal caregivers needs attention and possibly support. There was no indication that any aspects of ChEI therapy influenced the time spent in NHs.
|
|
| 3. |
|
|
| 4. |
- Wattmo, Carina, et al.
(författare)
-
Predictors of mortality in early- versus late-onset Alzheimer’s disease – an 18-year follow-up.
- 2018
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Few studies have focused on predictors of survival in patients with early-onset Alzheimer’s disease (EOAD) compared with late-onset Alzheimer’s disease (LOAD). We aimed to investigate the effect of genetic, sociodemographic, and clinical factors on mortality in the two groups.Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for longitudinal assessment of cholinesterase inhibitor (ChEI) therapy in clinical practice that includes 1,021 participants diagnosed with mild-to-moderate Alzheimer’s disease (AD) (Mini-Mental State Examination score, 10–26) at the start of ChEI treatment. Of these, 143 were defined as having EOAD (onset <65 years), 874 LOAD (onset >=65 years), and four missing age-at-onset; thus, 1,017 patients were included. Cox proportional hazards regression was used to determine characteristics that affected life expectancy: sex, apolipoprotein E genotype, solitary-living, duration of AD, age at baseline, years of education, specific concomitant medications, cognition (Alzheimer’s Disease Assessment Scale–cognitive subscale [ADAS-cog]) and activities of daily living (ADL) (Instrumental Activities of Daily Living scale [IADL] and Physical Self-Maintenance Scale [PSMS]) at baseline, and their rates of decline.Results: After 18 years of follow-up, 115 (80%) of the EOAD and 797 (91%) of the LOAD patients had died (p<0.001). In EOAD, males living alone, hazard ratio (95% confidence interval), 2.71 (1.18–6.22), p=0.019, lower IADL capacity at baseline, 1.07 (1.02–1.11), p=0.002, and faster rate of basic ADL deterioration/year 0.87 (0.77–0.98), p=0.026 independently predicted shorter survival. In LOAD, males of any living status 1.64 (1.41–1.92), p<0.001, older age at baseline, 1.04 (1.03–1.06), p<0.001, use of antihypertensive/cardiac therapy, 1.26 (1.09–1.47), p=0.002, use of antidiabetics, 1.51 (1.06–2.14), p=0.021, lower cognitive ability 1.02 (1.01–1.03), p<0.001 and worse basic ADL at baseline 1.05 (1.02–1.09), p=0.004, and faster rates of progression/year (ADAS-cog, 0.99 (0.98–0.99), p=0.004, PSMS, 0.92 (0.89–0.95), p<0.001) independently predicted shorter survival.Conclusions: Predictors of mortality differed between age groups. More impaired IADL, but not cognitive performance, was a risk factor for worse prognosis in EOAD. Solitary-living younger males exhibited nearly a threefold risk of death compared with corresponding males living with a family. In LOAD, demographic factors, cardiovascular comorbidities, and cognitive status had a significant impact on survival.
|
|
| 5. |
- Wattmo, Carina, et al.
(författare)
-
Predictors of mortality in patients with different apolipoprotein E genotypes—a 20-year follow-up of Alzheimer’s disease.
- 2021
-
Konferensbidrag (refereegranskat)abstract
- Background: To identify apolipoprotein E (APOE)-specific factors that may predict life expectancy after a diagnosis of Alzheimer’s disease (AD). Method: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, clinical-practice-based, multicentre study that includes 999 participants diagnosed with mild-to-moderate AD at the start of cholinesterase inhibitor (ChEI) therapy (time of diagnosis). Cognition and activities of daily living (ADL) were evaluated at baseline and semi-annually over 3 years, and the date of death was recorded. Result: After 20 years, 309/320 (97%) of the APOE non-ε4-carriers, 497/528 (94%) of the one-ε4-carriers, and 140/151 (93%) of the two-ε4-carriers had died (p=0.154). In the multivariate Cox regression models, risk factors for shorter lifespan in all patients were older age, lower cognitive ability at baseline, and faster cognitive decline/year. Moreover, a higher ChEI dose and/or longer treatment duration predicted increased survival. In APOE non-ε4-carriers, male sex, antidiabetic or antihypertensive/cardiac therapy, worse basic ADL at baseline, and faster instrumental ADL progression were observed to decrease life expectancy. In one-ε4-carriers, male sex, antihypertensive/cardiac therapy, and faster basic ADL deterioration predicted shorter survival. In two-ε4-carriers, antidiabetic use and longer AD duration were risk factors for decreased lifespan. Conclusion: Common risk factors for death, such as male sex, cardiovascular disorders, and functional impairment, were demonstrated in non-ε4-carriers and one-ε4-carriers, but not in two-ε4-carriers. The consequences of dementia, such as cognitive decline and duration of AD, may have a greater impact on survival in APOE two-ε4-carriers. Optimal ChEI treatment had positive effects in all patients irrespective of APOE genotype.
|
|
| 6. |
- Wattmo, Carina, et al.
(författare)
-
Prognostic regression models of life expectancy after diagnosis of Alzheimer’s disease – a 20-year follow-up.
- 2019
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: To determine characteristics that might affect survival times in Alzheimer’s disease (AD) patients treated with cholinesterase inhibitors (ChEI) in clinical practice, and create statistical models of estimated life-span after AD diagnosis. Method: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study to evaluate the use of long-term ChEI therapy. The SATS enrolled 1,021 participants with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination (MMSE) score, 10–26) at the start of ChEI treatment (shortly after AD diagnosis). Cognitive ability, instrumental and basic activities of daily living (ADL) were evaluated at baseline and semiannually over 3 years, and the date of death was recorded. Result: After up to 20 years of follow-up, 966 patients (95%) were deceased. Two types of multivariate linear regression models were created, one using only sociodemographic and clinical characteristics at baseline, and another model including baseline and longitudinal measures. Both main models included cognitive ability, and the extended models also included ADL capacities, as well as aspects of ChEI therapy in the longitudinal model. Significant independent predictors of longer life expectancy in all models were female sex, younger age, no use of antihypertensive/cardiac therapy or antidiabetics, (but not the specific apolipoprotein E genotype or solitary living), indicating the stability and validity of our regression models. A higher education level predicted shorter survival time in both baseline models (with and without ADL) and in the longitudinal model including cognition only. In the baseline model including ADL capacities, instrumental ADL (IADL) and basic ADL scores were stronger predictors of mortality than cognition. In the longitudinal model including ADL capacities, IADL and basic ADL scores (but not MMSE score) at baseline, progression rates in cognition and basic ADL predicted survival independently. A longer period of ChEI treatment in the study was also a strong predictor of longer life-span of up to ~2 years. Conclusion: The survival time after a diagnosis of AD could be predicted with a high degree of explanation using multivariate regression models including sociodemographic and clinical factors. These clinically relevant prognostic models can be used to estimate life expectancy for AD patients.
|
|
| 7. |
- Wattmo, Carina, et al.
(författare)
-
Risk factors for community-based home help services among patients with Alzheimer’s disease.
- 2012
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To identify factors that predict the use of community-based home help services in long-term cholinesterase inhibitor (ChEI)-treated patients with Alzheimer’s disease (AD). Methods: The Swedish Alzheimer Treatment Study (SATS) is an open, prospective, non-randomized, multicentre study in a routine clinical setting. Patients with AD living at home at the time of inclusion received treatment with donepezil, rivastigmine or galantamine. They were assessed with MMSE, IADL and PSMS scales at baseline and every 6 months over 3 years. The first 880 patients who had the opportunity to complete the full study were assessed regarding the use of home help services and adult day care. The following factors were investigated: gender, APOE e4 carrier status, living alone or with spouse, education level, age, illness duration and cognitive and functional level at baseline. Results: One hundred and thirty-nine patients (16%) received home help services at the start of ChEI treatment (average, 5.7 hours/week). After 3 years, 31% of the remaining 286 patients living at home used a mean of 8.7 h of home help/week. Among the patients with an MMSE score of 10–14, 8% of those living with a spouse used home help services compared with 62% of those living alone. Use of adult day care increased (from 3% to 19%) during the 3-year study among the patients without home help services; 89% of those using day care were not living alone. Solitary living (p<0.001), older age (p=0.004) and lower ADL abilities at baseline (p<0.001) were risk factors for use of home help services. These 4 variables correctly classified 90% of the patients regarding whether they used these services. Conclusions: Functional, but not cognitive, ability influenced the need for home help in AD patients. Solitary living, age and functional status predicted the use of community-based home help services with high accuracy. Patients not living alone seemed to use adult day care as a substitute for home help services.
|
|
| 8. |
- Wattmo, Carina, et al.
(författare)
-
Sex differences in predictors of cognitive and functional outcomes in patients with Alzheimer’s disease.
- 2019
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: About two-thirds of patients with Alzheimer’s disease (AD) are women, mostly because of their longer life-span and the higher prevalence of AD among older persons. A more-pronounced association between AD pathology and dementia (faster brain atrophy) and more-rapid cognitive decline have been reported in women. The AD prognosis might be affected by, e.g., size of cerebral hemispheres, role of sex hormones, cerebro- and cardiovascular comorbidities, psychiatric symptoms, and concomitant medications, which are all influenced by sex differences. A better cognitive response to cholinesterase inhibitors (ChEI) was observed in men compared with women. Thus, the predictors (genetic, sociodemographic, and clinical factors) of longitudinal cognitive and functional outcomes including aspects of ChEI treatment (e.g., drug agent, dose) may differ between sexes. In a study that included both sexes, our group previously found that male sex, older age, absence of the apolipoprotein E (APOE) e4 allele, use of nonsteroidal anti-inflammatory drugs (NSAIDs)/acetylsalicylic acids, and receiving a higher ChEI dose (regardless of type of drug), were independent predictors for a slower cognitive deterioration. Reports of sex-specific characteristics and effects of ChEIs that might affect the long-term course of AD are scarce. Objectives: This study aimed to identify sex-specific factors, including aspects of ChEI therapy, that may predict cognitive and functional progression rates in AD. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, open, nonrandomized multicenter study for the assessment of longitudinal effectiveness of ChEI therapy in a routine clinical setting. Among the 1,258 outpatients clinically diagnosed with probable or possible AD, 1,021 (367 men and 654 women) had mild-to-moderate AD (Mini-Mental State Examination [MMSE] score, 10–26) at the start of ChEI treatment (baseline) and were included in the current study. The participants were evaluated using cognitive tests (MMSE and Alzheimer’s Disease Assessment Scale–cognitive subscale [ADAS-cog]) and functional capacity scales (Instrumental Activities of Daily Living scale [IADL] and Physical Self-Maintenance Scale [PSMS]) at baseline and every 6 months for 3 years.Mixed, linear, and nonlinear fixed and random coefficient regression models were performed. The dependent variables were the scores (ADAS-cog, IADL, or PSMS) assigned at the second and subsequent visits for each individual. The following potential predictors were investigated: APOE genotype, solitary living, duration of AD, age at baseline, years of education, type of ChEI, dose of ChEI, specific concomitant medications (antihypertensive/cardiac therapy, antidiabetic drugs, asthma medication, thyroid therapy, lipid-lowering agents, estrogens, NSAIDs/acetylsalicylic acid, antidepressants, antipsychotics, and anxiolytics/sedatives/hypnotics), cognition, IADL, and basic ADL at baseline. Results: Better cognitive or IADL abilities at the initiation of ChEI treatment implied a slower cognitive decline over time in both sexes. An interaction effect showed that the difference in cognitive status at baseline between ages was more pronounced among older men (but not women) who were more cognitively impaired. In women, the absence of the APOE e4 allele or receiving NSAIDs/acetylsalicylic acid therapy were protective factors for a lower rate of cognitive progression. Regarding IADL, patients of both sexes with better cognitive performance at baseline exhibited a more favorable long-term outcome in IADL capacity. The use of antidepressants in men and solitary living in women predicted worsening IADL. In basic ADL, lower cognitive ability at baseline predicted a faster deterioration among both sexes. Women living alone demonstrated poorer prognosis in basic ADL. For women, there was a significant interaction effect in all three scales between time in months and years of education, i.e., a higher level of education implied increased cognitive or functional impairment over time. Men and women who received a higher mean dose of ChEI during the study showed a slower decline in cognitive ability, while men who received higher ChEI doses also exhibited lower progression rates in both IADL and basic ADL. Conclusion: The predictors of cognitive and functional deterioration differed between the sexes. Use of NSAIDs/acetylsalicylic acid was a protective factor for better cognitive outcome in women, which suggested that women might have greater cerebral inflammation and additional advantages of treatment with these drugs. Antidepressants in men and solitary living among women were risk factors for more-rapid worsening in IADL and basic ADL (only women living alone), which underlined the risk of apathy and social isolation among those individuals. Cognitive reserve capacity could have a larger impact on AD prognosis in women because a higher level of education implied increased cognitive or functional impairment over time. In women, the presence of the APOE e4 allele led to lower cognitive performance. These risk factors indicate more hereditary and advanced forms of AD in women. A higher mean dose of ChEI (irrespective of drug agent) was associated with slower cognitive decline in both sexes and lower functional progression rate among men, which might support the better ChEI response among men described previously. The findings stress the importance for clinicians to optimize the ChEI dose in AD regardless of sex to improve therapeutic effectiveness.
|
|
| 9. |
- Wattmo, Carina, et al.
(författare)
-
Sex differences in predictors of mortality in patients with Alzheimer’s disease – A 20-year follow-up.
- 2019
-
Konferensbidrag (refereegranskat)abstract
- Objectives: To identify sex-specific factors that may predict life expectancy after a diagnosis of Alzheimer’s disease (AD). Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study in clinical practice that includes 1,021 participants (367 males and 654 females) diagnosed with mild-to-moderate AD at the start of cholinesterase inhibitor treatment (time of diagnosis). Cognitive abilities and activities of daily living (ADL) were evaluated at baseline and semi-annually over 3 years, and the date of death was recorded. Cox proportional hazards regression was used to determine characteristics that affected survival: apolipoprotein E genotype, solitary living, duration of AD, age at baseline, years of education, specific concomitant medications, cognition, instrumental ADL (IADL) and basic ADL at baseline, and rates of decline. Results: After 20 years of follow-up, 346 (94%) of the male and 620 (95%) of the female AD patients had died (p=0.722). In Cox regression models, risk factors for shorter lifespan in all participants were: use of antihypertensive/cardiac therapy, older age, lower cognitive and basic ADL abilities at baseline and faster basal ADL deterioration/year. In males, more rapid IADL progression independently predicted shorter survival, whereas in females, the rate of cognitive decline and use of antidiabetics were found to decrease life expectancy. Conclusions: Predictors of mortality differed between sexes. A decline of ≥4 IADL points/year was a risk factor for worse prognosis among males, whereas a decline of ≥4 Mini-Mental State Examination points/year predicted earlier death among females. In females, antidiabetic therapy shortened mean survival by 17 months.
|
|
| 10. |
|
|
