Progression of Clinical Features in Lewy Body Dementia Can Be Detected Over 6 Months

Objective:This study aimed to quantify the trajectory and magnitude of change of the key clinical features and corresponding symptom domains of Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) including global cognition, parkinsonism, recurrent visual hallucinations, cognitive fluctuations and sleep disturbance.Methods:116 patients with Lewy body dementia (DLB=72, PDD=44) underwent assessment at baseline, 3 and 6 months as part of a prospective multi-centre randomized control trial. Linear mixed models were constructed for core outcome measures using the Mini-Mental State Examination (MMSE), motor section of the Unified Parkinson’s disease rating scale (UPDRS-III), Dementia Cognitive Fluctuations Scale (DCFS) and the Neuropsychiatric Inventory (NPI).Results:Within the timeframe of our study (6 months) we were able to identify a significant cognitive decline of 1.3 points on the MMSE (P=0.002) and significant worsening of motor parkinsonism with an increase in UPDRS-III score of 3.2 points (P=0.018). Fluctuation severity also increased using the DCFS with a 6 month change in score of 1.3 points (P=0.001). Uniquely, a signal for increased severity of sleep symptoms of 1.2 points (NPI-sleep) was also detectable (P=0.04). Significant changes in neuropsychiatric symptoms were not detected. There was no difference in rates of change of scores between DLB and PDD.Conclusions:Clinically significant rates of change in core clinical features can be detected and quantified in Lewy body dementia over a relatively short period (6 months) using common clinical instruments, and thus may be useful as clinical endpoints for therapeutic trials of disease modifying and symptomatic agents.

Clinical and functional impact of cognitive fluctuations in dementia

Cognitive fluctuations (CFs) are defined as spontaneous alterations in cognition, attention, and arousal, and are highly prevalent and disabling among people with dementia. CFs occur with a frequency of 80-90% in dementia with Lewy bodies (DLB), 40% in vascular dementia (VaD), and 20% in Alzheimer’s disease (AD). While CFs have been recognized as an important component of dementia, the majority of studies examining them have lacked objective methods of assessing their presence and severity, making it difficult to determine the degree of interference with other clinical features that can be attributable to fluctuations. The present study examined the nature and frequency of CFs in 55 individuals with dementia living in a long-term care facility. Participants underwent neuropsychological assessment to profile their current cognitive functioning. The Dementia Cognitive Fluctuation Scale (DCFS) was used to characterize CFs in this sample. Patients also completed brief cognitive measures on three separate occasions during a one-week period to obtain objective evidence of variability in cognitive performance. This study also assessed the association between CFs and informant based measures of patients’ quality of life, activities of daily living, and formal caregiver burden. Longitudinal cognitive data was analyzed retrospectively to determine patients’ rate of cognitive decline over the past six months. Consistent with the limited research already completed in this area, this study found that increasing severity of CFs predicts lower cognitive performance and reduced ability to complete activities of daily living. Also, this is the first study to demonstrate that CFs predict patients’ overall quality of life and the degree of caregiver burden in primary nursing staff. Results of the current study suggest that CFs exert a broad range of influence over patients’ functional abilities and well being. Identifying which patients experience CFs could play an important role in developing individualized treatment plans best suited for patients specific care needs.

Clinical and functional impact of cognitive fluctuations in dementia

Cognitive fluctuations (CFs) are defined as spontaneous alterations in cognition, attention, and arousal, and are highly prevalent and disabling among people with dementia. CFs occur with a frequency of 80-90% in dementia with Lewy bodies (DLB), 40% in vascular dementia (VaD), and 20% in Alzheimer’s disease (AD). While CFs have been recognized as an important component of dementia, the majority of studies examining them have lacked objective methods of assessing their presence and severity, making it difficult to determine the degree of interference with other clinical features that can be attributable to fluctuations. The present study examined the nature and frequency of CFs in 55 individuals with dementia living in a long-term care facility. Participants underwent neuropsychological assessment to profile their current cognitive functioning. The Dementia Cognitive Fluctuation Scale (DCFS) was used to characterize CFs in this sample. Patients also completed brief cognitive measures on three separate occasions during a one-week period to obtain objective evidence of variability in cognitive performance. This study also assessed the association between CFs and informant based measures of patients’ quality of life, activities of daily living, and formal caregiver burden. Longitudinal cognitive data was analyzed retrospectively to determine patients’ rate of cognitive decline over the past six months. Consistent with the limited research already completed in this area, this study found that increasing severity of CFs predicts lower cognitive performance and reduced ability to complete activities of daily living. Also, this is the first study to demonstrate that CFs predict patients’ overall quality of life and the degree of caregiver burden in primary nursing staff. Results of the current study suggest that CFs exert a broad range of influence over patients’ functional abilities and well being. Identifying which patients experience CFs could play an important role in developing individualized treatment plans best suited for patients specific care needs.

Cognitive fluctuations associated with therapy in patients with Parkinson diseases

The aim of the research is the assessment of cognitive status dynamics during levodopa pharmacotherapy. Material and methods. A new approach was created to assess cognitive status in patients with PD. It allows diagnosing cognitive fluctuations at an early stage at the highest quality level as well as to correct the disorders rationally and timely. The patients were randomized into two groups. In group 1 (n = 25), the assessment of cognitive status was carried out at the “peak” dose of levodopa and in 6 months at the state of levodopa dose “outcome”. In group 2 (n = 25), respectively, on the contrary, the initial assessment of cognitive status was carried out at the “outcome” of levodopa dose and in 6 months later at the “peak”. The study groups were comparable in terms of such parameters as: age, gender, average duration and stage of disease. On average, all the participants by the study time were at 2.5 stage of the disease according to Hoehn and Yahr scale; and the average length of the disease was 5 years. Results. Th e following statistically signifi cant results were obtained: in the fi rst group (peak–outcome) the average values on MMSE scale at the “peak” were 27 points; at the “outcome” they were – 25; MOCA values were 25 and 22 points, respectively; on FAB scale the values were – 16 and 14.5 points, SCOPA-Cog values were 33 and 28 points. In the second group (outcome – peak), the average values on MMSE scale at the “outcome” were 27, at the “peak” – 28, on MOCA scale – 23 and 25.5, respectively, on FAB scale – 16 and 17.5, SCOPA–Cog – 30 and 33. Conclusion. The present study confi rms that cognitive status of patient associated with antiparkinsonian therapy changes depending on the peak of levodopa and its outcome. At the peak of levodopa action, patients show signifi cantly better results on scaling, and at the end of the day, they demonstrate more significant cognitive impairments. A new two-stage method for assessing CF allows diagnosing cognitive impairments at a better level. Such method is necessary for timely initiation of therapy and rational correction of antiparkinsonian treatment.

Capturing Fluctuations in Gendered Cognition With Novel Intensive Longitudinal Measures

Cognition is often assumed to be stable, but compelling evidence shows that some skills (e.g., working memory) vary. There is limited investigation, however, of variation in gendered cognition, such as spatial skills and verbal recall, potentially because there are no validated measures for intensive longitudinal assessment. The goal of this study was to introduce and validate new 75-occasion measures of three-dimensional mental rotations and delayed paired verbal recall. This was accomplished by studying cognitive fluctuations over 75 days in an intensive longitudinal study of 121 participants, focusing on 54 (27 women) who were matched for gender, age, and language. Results from psychometric analyses suggest that both measures show parallel forms reliability, including expected gender differences, and validity (i.e., performance with respect to a standard measure or item difficulty), although results are more consistent for mental rotations than verbal recall. Results also suggest there are significant daily fluctuations in both mental rotations and verbal recall. Findings encourage future clinical work on the antecedents and consequences of cognitive fluctuations with the newly developed, freely available measures.

A review of the perceptual and attentional-executive characteristics of dementia with Lewy bodies relative to Alzheimer’s and Parkinson’s disease

Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia disorder, after Alzheimer’s disease (AD). DLB is characterised clinically by cognitive fluctuations, visual hallucinations, rapid-eye-movement sleep behaviour disorder, and Parkinsonism. Differentiating DLB from AD and related disorders of Parkinson’s disease (PD) and Parkinson’s disease with dementia (PDD) can be difficult at early disease stages due to overlapping clinical and pathological features. Nevertheless, it has been shown that visuoperceptual, attention and executive deficits, relative to memory impairments, are especially prominent in the early stages of DLB compared with AD or PD. The importance of these impairments is reflected in the recent revision of the diagnostic consensus guidelines of DLB. As the last reviews of cognitive impairments in DLB were conducted over a decade ago (Collerton, Burn, McKeith & O’Brien, 2003; Metzler-Baddeley, 2007; Ralph, 2001), we provide an up-to-date review of the literature into perceptual and attention-executive functions in DLB. There is a need for better controlled studies into cognitive deficits, their neural correlates, and relationships to clinical symptoms in DLB, that go beyond standard clinical assessments. Evidence regarding visuoperception suggests that low-level functions may be relatively preserved while mid- and higher-level functions, that require the recruitment of attention and executive functions are disproportionally affected in DLB. Cognitive fluctuations and visual hallucinations may arise from a desynchronization of top-down attention and bottom-up sensory networks.

Evaluating the Sustained Attention Response Task to Quantify Cognitive Fluctuations in Dementia With Lewy Bodies

Cognitive fluctuations (CFs) are a core diagnostic feature of dementia with Lewy bodies (DLB). Detection of CF is still mostly based on subjective reports from the patient or informant; more quantitative measures are likely to improve the accuracy for the diagnosis of DLB. The purpose of the current study is to test whether performance on the Sustained Attention Response Task (SART) could distinguish those patients with DLB with and without CF. Twenty-four patients with DLB were tested on the SART and performance was related to scores on the Clinical Assessment of Fluctuations (CAFs) and One Day Fluctuation Assessment Scale (ODFAS). The number of “misses” made was a significant predictor of their fluctuation severity, attentional performance, disorganized thinking, and language production ratings on the ODFAS. However, measures on the SART did not correlate with measures on the CAF scale. In conclusion, these findings suggest that SART is a feasible measure of sustained attention in this population and has clinical and diagnostic relevance to the measurement of CF, particularly those aspects measured by the ODFAS.