Dementia with Lewy bodies - a clinical and neurological approach

Dementia with Lewy bodies (DLB) is a dementia disorder, clinically characterized by fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism and other neuropsychiatric features. Sensitivity to neuroleptic medication is a common finding. In the present study 24% of 200 autopsied cases, within the Lund longitudinal prospective dementia study fulfilled the clinical diagnostic criteria of DLB. Compared to clinical Alzheimer (AD) cases, these cases also showed clinical signs of frontal dysfunction. Furthermore they had a greater degree of deterioration of dementia and were more reliant on outside assistance when compared to clinical AD cases. The blood pressure decreased during dementia and many cases became hypotensive and orthostatic. The pharmacological load was heavier in clinical DLB compared to AD. The neuropathological results revealed Lewy bodies in 38% of the clinically defined DLB cases. These cases also had other pathological changes such as Alzheimer pathology, vascular pathology and a degeneration of dopaminergic and cholinergic nuclei, eg substantia nigra and nucleus basalis Meynert. Clinical DLB cases lacking Lewy bodies were characterised by Alzheimer pathology combined with frontally selective incomplete white matter infarcts. EEG and regional cerebral blood flow measurements were not helpful in distinguishing between AD and DLB or in separating cases with Lewy body pathology from those without. When individual cases were analysed clinico-pathologically, the DLB symptoms could often be explained by the combinations of pathologies. The study illustrates the difficulties of the clinical recognition of a specific pathological entity in individuals and the complex relation between brain pathology, clinical symptoms, medication and its adverse effects

The interaction effect of sex and apolipoprotein E genotype in Alzheimer’s disease—rates of progression and prognosis.

Objectives: To investigate the interaction effect of sex and apolipoprotein E (APOE) genotype on long-term cognitive and functional outcomes and survival in Alzheimer’s disease (AD). Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study in clinical practice involving 999 participants diagnosed with mild-to-moderate AD at the start of cholinesterase inhibitor treatment (time of diagnosis). The patients were evaluated using Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS–cog), Instrumental Activities of Daily Living scale (IADL) and Physical Self-Maintenance Scale (PSMS) at baseline and semi-annually over 3 years, and date of death was recorded for 20 years. Results: The frequency of APOE ε4-carriers differed between sexes, 60% of males and 73% of females had 1 or 2 alleles (p < 0.001). The ε4-carriers were younger than non-ε4-carriers at the estimated onset of AD and at diagnosis in both sexes, and younger at death in males. After 3 years, decline in ADAS–cog was faster in both female APOE ε4-carriers, mean (95% confidence interval), 8.2 (6.5–9.8) and non-ε4-carriers 9.4 (6.4–12.3) points, than in male non-ε4-carriers 3.8 (0.9–6.7) points, (p = 0.036). Functional deterioration was faster in female non-ε4-carriers than in male non-ε4-carriers, IADL: 8.1 (6.8–9.4) vs. 4.9 (3.6–6.2) points (p = 0.007), and PSMS: 3.8 (3.0–4.7) vs. 2.2 (1.3–3.0) points (p = 0.033). These differences were not detected among ε4-carriers. Conclusions: The effect of APOE genotype differed between sexes in AD. Male ε4-carriers showed 2 years earlier death than male non-ε4-carriers. Female non-ε4-carriers demonstrated worse cognitive and functional prognosis than male non-ε4-carriers

Solitary living in Alzheimer's disease over 3 years: association between cognitive and functional impairment and community-based services.

Introduction: Many individuals with Alzheimer’s disease (AD) live alone, and this figure is expected to increase. This study aimed to describe the cognitive and functional abilities of solitary-living AD patients, and the potential predictors of their usage of community-based services. Methods: This 3-year, prospective, multicenter study included 1,021 participants with mild-to-moderate AD (Mini-Mental State Examination score, 10–26) treated with cholinesterase inhibitors (ChEI) in a routine clinical setting. At the baseline and every 6 months, patients were assessed using cognitive, instrumental and basic activities of daily living (ADL) scales, and service utilization was recorded. Logistic regression models were used to predict the usage of community-based services. Results: At the start of ChEI therapy (time of AD diagnosis), 355 individuals (35%) were living alone. They were mainly female, older, had more impaired basic ADL capacity, and a larger number of concomitant medications compared with those living with family. Regarding the solitary-living patients, lower instrumental ADL (IADL) ability and more medications were independent predictors of usage of home-help services, whereas more impaired IADL at baseline and faster IADL deterioration were predictors of nursing-home admission. For those living with family, older age, lower basic ADL, and a greater number of medications predicted home-help services, whereas a larger amount of home help predicted nursing-home placement. In addition, female sex was a risk factor for both the utilization of home-help services and nursing-home placement. Cognitive ability was not significantly associated with usage of community-based services. Conclusions: A large number of AD patients, predominantly females, live alone with severe cognitive and functional impairment. The amount of home-help services used did not reflect cognitive severity, suggesting that home help did not meet the needs related to cognitive deterioration. Increased knowledge of how community-based services can better accommodate the care needs of solitary-living individuals with AD is essential

The effect of functional capacity and concomitant medications on life expectancy in Alzheimer’s disease.

Background: An increased knowledge of predictors that might affect survival in Alzheimer’s disease (AD) patients treated with cholinesterase inhibitors (ChEIs) is important for clinicians and for the health services. Impairment in activities of daily living (ADL), somatic diseases, and psychiatric symptoms may influence mortality in AD. We aimed to study the impact of functional capacity and concomitant medications on patient life expectancy in clinical practice. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for the long-term assessment of ChEI treatment. This study included 791 deceased participants with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination score, 10–26) at the start of ChEI therapy (shortly after diagnosis). Patients were evaluated regarding cognitive and functional abilities and concomitant medications. The date of death was recorded. Survival was compared individually with that of the sex- and age-matched general population. Results: The mean ± SD time from AD diagnosis to death was 5.7 ± 2.8 years and varied among patients with different levels of instrumental ADL (IADL) impairment at baseline, from 6.6 ± 2.8 years (IADL score, 8–12) to 5.0 ± 2.5 years (IADL score, 21–31) (P < 0.001). The time from AD diagnosis to death also differed between patients receiving antihypertensive/cardiac therapy (no/yes, 6.1 ± 2.7 vs 5.3 ± 2.8 years; P < 0.001), antidiabetics (no/yes, 5.8 ± 2.8 vs 4.1 ± 2.4 years; P < 0.001), nonsteroidal anti-inflammatory drugs (NSAIDs)/acetylsalicylic acid; no/yes, 6.0 ± 2.8 vs 5.2 ± 2.6 years; P < 0.001), and antipsychotics (no/yes, 5.8 ± 2.8 vs 4.7 ± 2.5 years; P = 0.020). IADL score at baseline and antihypertensive/cardiac therapy, antidiabetics, and antipsychotics were independent predictors of survival after AD diagnosis in a general linear model, after controlling for sex, age, and cognitive ability. Basic ADL, number of medications, and specific concomitant medications (lipid-lowering agents, NSAIDs/acetylsalicylic acid, antidepressants, and anxiolytics/sedatives/hypnotics) at baseline were not significant predictors. Conclusions: IADL, but not basic ADL, was an important predictor that should be considered by clinicians and community-based services when estimating AD prognosis. Antidiabetic therapy was a strong risk factor for reduction in life expectancy

Various outcomes of cholinesterase inhibitor treatment influence survival of patients with Alzheimer’s disease.

Objectives: Various outcomes of cholinesterase inhibitor (ChEI) therapy have been observed in Alzheimer’s disease (AD). It is not clear whether the duration of treatment, type of ChEI, or dose affect mortality. We aimed to investigate the association between ChEI therapy and patient survival. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study to evaluate long-term treatment with ChEIs in clinical practice. This study included 1021 outpatients with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination score, 10–26) at the start of ChEI treatment (shortly after diagnosis). The date of death of participants was recorded. Results: After up to 16 years of follow-up, 841 (82%) of the patients in the SATS had died. The mean ± standard deviation time from diagnosis of AD to death was 6.0 ± 2.9 years, and differed between individuals with varying durations of ChEI treatment in the study, from 7.2 ± 2.5 years (3-year completers) to 4.9 ± 2.9 years (<1 year) (P<0.001). Patients who received a higher mean dose of ChEIs during the study had a longer lifespan than those who received a lower dose (6.4 ± 2.9 vs 5.5 ± 2.8 years; P<0.001). The median cutoff values were donepezil 6.9 mg, rivastigmine 6.0 mg, and galantamine 15.0 mg. No difference in mortality between the types of ChEIs was found after adjusting for sex, age, and disease severity. Conclusions: Longer survival can be expected for AD patients who receive and tolerate higher ChEI doses and a longer duration of treatment

Dementia with Lewy Body (DLB) Symptoms Hidden within the Diagnosis “Dementia Not Otherwise Specified” a Cross-Sectional Study in 40 Swedish Nursing Homes.

Background: Dementia with Lewy Body (DLB) is a neurocognitive disorder with core features, such as Parkinsonism, visual hallucinations, and fluctuating cognition/ excessive daytime sleepiness, and supportive features, such as rapid eye movement sleep behaviour disorder. DLB is often misdiagnosed and unrecognized in elderly individuals. A diagnosis of DLB is important because of the risk of hypersensitivity for neuroleptic drugs. Moreover, appropriate treatment of symptoms can improve quality of life considerably for both the individual with DLB and their caregivers. Primary care uses often diagnose Dementia Not Otherwise Specified (NOS) that may lead to an increased risk of wrong medical treatment and lack of proper elderly care. Especially if the elderly had a misdiagnosed or undefined DLB symptomatology. We hypothesized that potential DLB symptoms were hidden within the Dementia NOS diagnosis. Methods: A questionnaire designed to cover the main DLB symptoms (according to DLB consensus criteria from 2005) was distributed to all 40 primary care nursing homes (NHs) and geographically entirely covering the third largest Swedish city. Nursing staff completed the questionnaires after receiving specifically designed teaching. Results: The participants were elderly (n=650) from all NHs (n=40) where 94% (n=610) were included of which (n=595) had available medical records. The mean age was 86.0 ± 7.5 years; 75% (n=467) were women. The prevalence of elderly with Dementia NOS was 20% (n=121), AD 19% (n=115), AD-Mix 16% (n=97), VaD 14% (n=85), DLB/PDD 5% (n=22) and in 26% (n=155) no formal dementia diagnosis was found. Finally, according to the questionnaire, 16% of all the participants had two or more main symptoms of DLB (2-4 DLB smp.) According to the questionnaire, the elderly with the Dementia NOS diagnosis 85% had 0-1 DLB smp. and 15% had 2-4 DLB smp. Conclusion: We conclude that within the dementia NOS diagnose elderly with hidden DLB symptoms constitute 15% leading to risk of potentially harmful medication. Recognizing signs of dementia with Lewy bodies could reduce the number of individuals with Dementia NOS diagnosis and give opportunity to more suitable and less potentially harmful medication in nursing homes

A longitudinal study of risk factors for community-based home help services in Alzheimer's disease: the influence of cholinesterase inhibitor therapy

Background: To investigate the long-term effects of cholinesterase inhibitor (ChEI) therapy and the influence of sociodemographic and clinical factors on the use of community-based home help services (HHS) by patients with Alzheimer's disease (AD). Methods: This 3-year, prospective, multicenter study included 880 AD patients treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every 6 months, the patients were assessed with several rating scales, including the Mini-Mental State Examination, Instrumental Activities of Daily Living (IADL), and Physical Self-Maintenance Scale. Doses of ChEI and amounts of HHS per week were recorded. Cox regression models were used to predict the time to HHS, and multiple linear regression was used to predict the volume of HHS used. Results: During the study, 332 patients (38%) used HHS. Factors that both postponed HHS use and predicted lower amounts of HHS were higher doses of ChEIs, better IADL ability, and living with family. Men, younger individuals, and those with a slower IADL decline showed a longer time to HHS, whereas female sex, a lower cognitive status, or more medications at baseline predicted fewer hours of HHS. Conclusions: Higher doses of ChEI might reduce the use of HHS, possibly reducing the costs of community-based care. Female spouses provide more informal care than do male spouses, so the likelihood of using HHS is greater among women with AD. The "silent group" of more cognitively impaired and frail elderly AD patients receives less HHS, which might precipitate institutionalization

Predictors of long-term cognitive outcome in Alzheimer's disease

Introduction: The objective of this study was to describe the longitudinal cognitive outcome in Alzheimer’s disease (AD) and analyze factors that affect the outcome, including the impact of different cholinesterase inhibitors (ChEI). Methods: In an open, three-year, nonrandomized, prospective, multicenter study, 843 patients were treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every six months, patients were assessed using several rating scales, including the Mini-Mental State Examination (MMSE) and the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and the dose of ChEI was recorded. Sociodemographic and clinical characteristics were investigated. The relationships of these predictors with longitudinal cognitive ability were analyzed using mixed-effects models. Results: Slower long-term cognitive decline was associated with a higher cognitive ability at baseline or a lower level of education. The improvement in cognitive response after six months of ChEI therapy and a more positive longitudinal outcome were related to a higher mean dose of ChEI, nonsteroidal anti-inflammatory drug (NSAID)/ acetylsalicylic acid usage, male gender, older age, and absence of the apolipoprotein E (APOE) ε4 allele. More severe cognitive impairment at baseline also predicted an improved response to ChEI treatment after six months. The type of ChEI agent did not influence the short-term response or the long-term outcome. Conclusions: In this three-year AD study performed in a routine clinical practice, the response to ChEI treatment and longitudinal cognitive outcome were better in males, older individuals, non-carriers of the APOE ε4 allele, patients treated with NSAIDs/acetylsalicylic acid, and those receiving a higher dose of ChEI, regardless of the drug agent

A Quick Test of cognitive speed is sensitive in detecting early treatment response in Alzheimer's disease

Introduction There is a great need for quick tests that identify treatment response in Alzheimer's disease (AD) to determine who benefits from the treatment. In this study, A Quick Test of cognitive speed (AQT) was compared with the mini-mental state examination (MMSE) in the evaluation of treatment outcome in AD. Methods 75 patients with mild to moderate AD at a memory clinic were assessed with AQT and the MMSE at a pretreatment visit, at baseline and after 8 weeks of treatment with cholinesterase inhibitors (ChEI) initiated at baseline. Changes in the mean test scores before and after treatment were compared, as well as the number of treatment responders detected by each test, according to a reliable change index (RCI). Results After 8 weeks of treatment, the AQT improvement, expressed as a percentage, was significantly greater than that of the MMSE (P = 0.026). According to the RCI, the cut-offs to define a responder were ≥16 seconds improvement on AQT and ≥3 points on the MMSE after 8 weeks. With these cut-offs, both tests falsely classified ≤5% as responders during the pretreatment period. After 8 weeks of treatment, AQT detected significantly more responders than the MMSE (34% compared with 17%; P = 0.024). After 6 months of treatment, the 8-week AQT responders still showed a significantly better treatment response than the AQT nonresponders (22.3 seconds in mean difference; P < 0.001). Conclusions AQT detects twice as many treatment responders as the MMSE. It seems that AQT can, already after 8 weeks, identify the AD patients who will continue to benefit from ChEI treatment

Treatment effect of memantine on survival in dementia with Lewy bodies and Parkinson's disease with dementia: a prospective study.

To investigate the effect on survival of treatment with memantine in patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD)