Search

Background: Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD)., Methods: A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function., Results: Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline., Conclusions: These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms - particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.

Objective: We explored whether the mild cognitive impairment (MCI) stages of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) differ in their cognitive profiles, and longitudinal progression., Design: A prospective, longitudinal design was utilized with annual follow-up (Max 5 years, Mean 1.9, standard deviation 1.1) after diagnosis. Participants underwent repeated cognitive testing, and review of their clinical diagnosis and symptoms, including evaluation of core features of DLB., Setting: This was an observational study of independently living individuals, recruited from local healthcare trusts in North East England, UK., Participants: An MCI cohort (n = 76) aged ≥60 years was utilized, differentially diagnosed with MCI due to AD (MCI-AD), or possible/probable MCI with Lewy bodies (MCI-LB)., Measurements: A comprehensive clinical and neuropsychological testing battery was administered, including ACE-R, trailmaking tests, FAS verbal fluency, and computerized battery of attention and perception tasks., Results: Probable MCI-LB presented with less impaired recognition memory than MCI-AD, greater initial impairments in verbal fluency and perception of line orientation, and thereafter demonstrated an expedited decline in visuo-constructional functions in the ACE-R compared to MCI-AD. No clear diagnostic group differences were found in deterioration speeds for global cognition, language, overall memory, attention or other executive functions., Conclusion: These findings provide further evidence for differences in severity and decline of visuospatial dysfunctions in DLB compared with AD; further exploration is required to clarify when and how differences in attention, executive, and memory functions emerge, as well as speed of decline to dementia., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: dementia risk conferred by apolipoprotein-E (APOE) and angiotensin-1-converting enzyme (ACE) polymorphisms have been reported for the MRC Cognitive Function and Ageing Study (CFAS) at 6-year follow-up. We concentrate on incident dementia risk over 10 years., Methods: participants come from MRC CFAS, a multi-centre longitudinal population-based study of ageing in England and Wales. Three follow-up waves of data collection were used: 2, 6 and 10 years. Logistic regressions were undertaken to investigate associations between APOE (n = 955) and ACE (n = 856) alleles/genotypes and incident dementia. Two types of control groups were used: non-demented and highly functioning non-demented. Results were back-weighted., Results: compared to APOE epsilon3, epsilon2 conferred protection of odds ratio (OR) = 0.3 (95% confidence interval, CI = 0.1-0.6) and epsilon4 risk of OR = 2.9 (95% CI = 1.7-4.9) for incident dementia. Compared to epsilon3/epsilon3, the epsilon3/epsilon4 and epsilon4/epsilon4 genotypes conferred risks of OR = 3.6 (95% CI = 1.8-7.3) and OR = 7.9 (95% CI = 1.6-39.2), respectively. The epsilon3/epsilon2 genotype protected against dementia (OR = 0.2, 95% CI = 0.1-0.7), and epsilon2/epsilon2 had a similar protective effect but with wide CIs (OR = 0.3, 95% CI = 0.1-1.7). Restricting the control group accentuated these differentials. The effects of ACE alleles/genotypes on incident dementia risk were small., Conclusions: APOE but not ACE is associated with late-onset incident dementia in the population. Using longer term follow-up with proper adjustment for attrition and incident cases increases estimates of risk.

Objective: The etiology of Parkinson disease (PD) is complex and multifactorial, with hereditary and environmental factors contributing. Monogenic forms have provided molecular clues to disease mechanisms but genetic modifiers of idiopathic PD are still to be determined., Methods: We carried out whole-genome expression profiling of isolated human substantia nigra (SN) neurons from patients with PD vs. controls followed by association analysis of tagging single-nucleotide polymorphisms (SNPs) in differentially regulated genes. Association was investigated in a German PD sample and confirmed in Italian and British cohorts., Results: We identified four differentially expressed genes located in PD candidate pathways, ie, MTND2 (mitochondrial, p = 7.14 x 10(-7)), PDXK (vitamin B6/dopamine metabolism, p = 3.27 x 10(-6)), SRGAP3 (axon guidance, p = 5.65 x 10(-6)), and TRAPPC4 (vesicle transport, p = 5.81 x 10(-6)). We identified a DNA variant (rs2010795) in PDXK associated with an increased risk of PD in the German cohort (p = 0.00032). This association was confirmed in the British (p = 0.028) and Italian (p = 0.0025) cohorts individually and reached a combined value of p = 1.2 x 10(-7) (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.18-1.44)., Interpretation: We provide an example of how microgenomic genome-wide expression studies in combination with association analysis can aid to identify genetic modifiers in neurodegenerative disorders. The detection of a genetic variant in PDXK, together with evidence accumulating from clinical studies, emphasize the impact of vitamin B6 status and metabolism on disease risk and therapy in PD.

Objectives: To determine the 2-year outcome from 16 different current classifications of mild cognitive impairment (MCI) in a population-based sample., Design: Prospective cohort study: baseline and 2-year follow-up phases., Setting: Large-scale multicenter study, United Kingdom., Participants: : Thirteen thousand four individuals aged 65 and older from the Medical Research Council Cognitive Function and Ageing Study. From this, a subsample of 2,640 individuals was selected and completed a more-detailed cognitive assessment. Individuals who underwent further assessment were asked to complete annual or 2-year follow-ups., Measurements: Information on sociodemographic status, general health, cognitive impairment and functional ability were collected using a structured interview. Individuals were classified according to 16 different definitions of MCI. These were applied retrospectively., Results: The dominant outcome across definitions was an impairment that was not classifiable or reversion to normality. Progression to dementia was variable and generally poor. Overall progression was highest in classifications in which impairment extended to memory and nonmemory domains. Predictability was age dependent in some but not all classifications., Conclusion: Current classifications of MCI have variable outcomes in population-based samples. Progression to dementia is relatively rare and is dependent on age and definition. Selection criteria developed for the clinic are based on a "high risk" approach that leads to exclusion of a large percentage of the impaired population who are neither normal nor demented and for whom no intervention options are currently available. A refined definition of this construct is urgently needed if MCI is to be used to predict dementia in population-based studies.

The authors recently have shown that triplication of the alpha-synuclein gene (SNCA) can cause Parkinson disease (PD) and diffuse Lewy body disease within the same kindred. The authors assessed 101 familial PD probands, 325 sporadic PD cases, 65 patients with dementia with Lewy bodies, and 366 neurologically normal control subjects for SNCA multiplication. The authors did not identify any subjects with multiplication of SNCA and conclude this mutation is a rare cause of disease.

Background: Few data are available regarding the natural course of psychiatric symptoms in dementia with Lewy bodies and Alzheimer's disease. To acquire this information is essential to inform differential diagnosis and treatment decisions., Method: The current study provides prospective data regarding a representative case-register cohort of patients with operationalized clinical diagnoses of dementia with Lewy bodies (N = 82) or Alzheimer's disease (N = 132), with verified accuracy of clinical diagnosis against postmortem examination. Psychosis (Columbia University Scale for Psychopathology in Alzheimer's Disease) and depression (Cornell Scale for Depression in Dementia) were assessed at baseline and annual follow-up., Results: Visual hallucinations were significantly more likely to be persistent in patients suffering from dementia with Lewy bodies (chi2 = 19.1, df = 1, p < .0001). Although a number of other psychiatric symptoms were also more frequent at baseline in dementia with Lewy body patients, they were not significantly more likely to persist. Delusions and auditory hallucinations did, however, persist in more than 40% of patients across both diagnostic groups. Patients suffering from dementia with Lewy bodies were significantly more likely to develop new auditory hallucinations over the year of follow-up (chi2 = 14.4, df= 1, p < .0001)., Conclusion: These results confirm that, although a number of psychiatric symptoms are common in dementia with Lewy bodies, it is only visual hallucinations that are significantly more persistent, with important treatment implications.

Background: The identification of fluctuating confusion is central to improving the differential diagnosis of the common dementias., Aims: To determine the value of two rating scales to measure fluctuating confusion., Method: The agreement between the clinician-rated scale and the scale completed by a non-clinician was determined. Correlations between the two scales were calculated; variability in attention was calculated on a computerised cognitive assessment and variability in delta rhythm on an electroencephalogram (EEG)., Results: The Clinician Assessment of Fluctuation and the computerised cognitive assessment were completed for 155 patients (61 Alzheimer's disease, 37 dementia with Lewy bodies, 22 vascular dementia, 35 elderly controls). A subgroup (n = 40) received a further evaluation using the One Day Fluctuation Assessment Scale and an EEG. The two scales correlated significantly with each other, and with the neuropsychological and electrophysiological measures of fluctuation., Conclusions: Both scales are useful instruments for the clinical assessment of fluctuation in dementia.

Background: little is known about the longitudinal course of dementia with Lewy bodies (DLB) and how this differs from Alzheimer's disease (AD)., Method: standardized baseline and annual assessments of cognitive and non-cognitive symptoms are reported in a cohort of 72 patients with DLB or AD. AD was diagnosed using the NINCDS ADRDA criteria and DLB was diagnosed with the criteria of McKeith et al. Cognitive assessment was undertaken using the MMSE schedule and operationalized definitions were used to diagnose non-cognitive symptoms., Results: 42 patients with DLB and 30 patients with AD were assessed. Of the 19 on whom post mortem examinations have been performed, 18 (95%) have had the clinical diagnosis confirmed. DLB patients were significantly more likely to experience visual hallucinations, disturbances of consciousness and parkinsonism at both baseline and at annual assessments. Of DLB patients exposed to neuroleptics, 33% developed sensitivity reactions. The magnitude and pattern of cognitive decline was similar in both groups., Conclusion: the importance of the core features highlighted in the newly proposed consensus DLB criteria is supported. These features appear to be stable over time.