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Introduction: Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). Methods: This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer’s Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. Results: The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. Discussion/Conclusion: TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.

Objective: To examine the impact of selective serotonin reuptake inhibitors (SSRIs) and depression on neurogenesis and cognition in dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). Methods: Late-stage progenitor cells were quantified in the subgranular zone (SGZ) of the hippocampal dentate gyrus of DLB/PDD patients (n = 41) and controls without dementia (n = 15) and compared between treatment groups (unmedicated, SSRIs, acetyl cholinesterase inhibitors [AChEIs], combined SSRIs and AChEIs). Results: DLB/PDD patients had more doublecortin-positive cells in the SGZ compared to controls. The doublecortin-positive cell count was higher in the SGZ of patients treated with SSRIs and correlated to higher cognitive scores. Conclusion: SSRI treatment was associated with increased hippocampal neurogenesis and preservation of cognition in DLB/PDD patients.

Aims: To examine the effects of galantamine and risperidone on agitation in patients with dementia. Methods: A total of 100 patients with dementia and neuropsychiatric symptoms (mean age ± SD: 78.6 ± 7.5 years; 67% female) were included in this 12-week, randomized, parallel-group, controlled, single-center trial. The participants received galantamine (n = 50; target dose: 24 mg) or risperidone (n = 50; target dose: 1.5 mg) for 12 weeks. Results: Both galantamine and risperidone treatment resulted in reduced agitation. However, risperidone showed a significant advantage over galantamine both at week 3 (mean difference in total Cohen-Mansfield Agitation Inventory score: 3.7 points; p = 0.03) and at week 12 (4.3 points; p = 0.01). Conclusions: Agitation improved in both groups, even if the treatment effects were more pronounced in the risperidone group; however, the effects on cognition and other aspects of tolerability were stronger with galantamine.

Background/Aims: Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the two most common neurodegenerative dementias. During the early stages, clinical distinction between them is often challenging. Our objective is to compare hippocampal atrophy patterns in mild AD and mild DLB. We hypothesized that DLB subjects have milder hippocampal atrophy relative to AD subjects. Methods: We analyzed the T1-weighted magnetic resonance imaging data from 113 subjects: 55 AD, 16 DLB and 42 cognitively normal elderly (normal controls, NC). Using the hippocampal radial distance technique and multiple linear regression, we analyzed the effect of clinical diagnosis on hippocampal radial distance, while adjusting for gender and age. Three-dimensional statistical maps were adjusted for multiple comparisons using permutation-based statistics with a threshold of p Results: Compared to NC, AD exhibited significantly greater atrophy in the cornu ammonis (CA)1, CA2–3 and subicular regions bilaterally while DLB showed left-predominant atrophy in the CA1 region and subiculum. Compared directly, AD and DLB did not reveal statistically significant differences. Conclusion: Hippocampal atrophy, while present in mildly impaired DLB subjects, is less severe than atrophy seen in mildly impaired AD subjects, when compared to NC. Both groups show predominant atrophy of the CA1 subfield and subiculum.

Aim: To investigate quality of life (QOL) and the effect of memantine treatment in patients with Lewy body dementias. Methods: A secondary analysis of a randomized controlled study in 70 patients with Parkinson’s disease dementia (PDD) or dementia with Lewy bodies (DLB) over 24 weeks using caregiver-rated QOL-Alzheimer’s disease (AD) in domains according to the WHO’s classification of health. Results: Baseline QOL shows lower ratings for body functions over environmental factors in DLB/PDD. Treatment with memantine significantly improves life as a whole compared to placebo and improves total QOL, body function and structure. Conclusion: This study shows that memantine improves QOL in Lewy body dementias. We also demonstrate important QOL patterns which can be used in clinical practice.

Objective: To explore the course of depression in people with mild dementia and identify predictors for depression at 1-year follow-up. Methods: Patients with mild dementia (n = 199) were assessed using Montgomery and Åsberg Depression Rating Scale (MADRS) and the depression item from Neuropsychiatric Inventory (NPI) at baseline and after 1 year. A score above 6 on MADRS indicates at least mild depression. Linear and logistic regression analyses were performed to identify predictors of change in depression scores. Results: Among subjects with depression at baseline, 68.1% remained depressed at follow-up, whereas 31.9% had remitted, based on MADRS. Among patients without depression at baseline, 77.1% remained non-depressed at follow-up, whereas 22.9% had incident depression. The proportion with persistent depression was higher in the combined dementia with Lewy bodies (DLB)/Parkinson’s disease with dementia (PDD) group (45.5%) compared to AD (28%) (p < 0.05). Greater decline on the Mini Mental State Examination (p < 0.001) and higher baseline MADRS score (p < 0.001) were significant predictors of increased MADRS score. Conclusion: Two thirds of patients with depression at baseline were still depressed at follow-up, more so in DLB with PDD compared to AD. Cognitive decline was associated with worsening of depressive symptoms.

Aims: To investigate the effects of rivastigmine capsule 3–12 mg/day over 24 weeks on activities of daily living (ADLs) in patients with dementia associated with Parkinson’s disease (PDD). Methods: Post hocanalysis of a prospective, multicenter, randomized, double-blind, placebo-controlled trial in patients with PDD (≧50 years) randomized to rivastigmine 3–12 mg/day (capsules bid) or placebo over 24 weeks. This analysis was carried out with three subscales derived from a factor analysis of the 23 items in the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) scale. These subscales were basic ADLs (10 items), high-level function ADLs (eight items) and autonomy ADLs (five items). Results: 541 patients were randomized (362 to rivastigmine, 179 to placebo) and 410 (75.8%) completed the study. Rivastigmine was associated with significantly better outcomes in basic ADLs (–0.5 ± 6.19 vs. –1.7 ± 5.46; p = 0.025; effect size 22.1%) and high-level function ADLs (0.1 ± 4.95 vs. –1.0 ± 4.49; p = 0.017; effect size 22.9%) compared with placebo, at week 24. Conclusion: In patients with PDD, treatment with rivastigmine may show beneficial effects on overall ADLs, as well as modest, statistically significant improvements in basic ADLs and high-level function ADLs.

Background: The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer’s disease (AD). Method: We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB. Results: The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid β (aβ) isoforms as well as α-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level. Conclusion: Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

Background: Serotonin 1A receptors (5-HT1A) have not been studied in dementia with Lewy bodies (DLB) or Parkinson’s disease dementia (PDD) patients with depression. Aim: To examine 5-HT1A in DLB and PDD postmortem in relation to depression. Methods: [3H]8-hydroxy-2-dipropylaminotetralin binding to 5-HT1A was determined in temporal cortex (Brodmann areas, BA20 and BA36) from 10 DLB patients, 17 PDD patients and 9 controls. Results: 5-HT1A density was significantly higher in BA36 in combined DLB/PDD patients with depression, but was unaltered in BA20. Conclusion: Higher BA36 5-HT1A density in PDD and DLB patients than in control is dependent on whether the patient had experienced depression during life, not DLB/PDD diagnosis. A 5-HT1A antagonist adjuvant may improve treatment of depression in dementia.

Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) are common clinical dementias characterized neuropathologically by the presence of cortical Lewy body pathology and with distinct clinical and neurobiological similarities. Importantly, genetic factors seem to play a key role in the pathogenesis of Parkinson’s disease. In the current article, we examine the evidence for a genetic component to DLB and PDD by reviewing studies of familial PDD and DLB as well as familial coincidental PDD and DLB, and report the genes involved. There is a convincing genetic overlap between both syndromes, suggesting that they share a common etiological factor.

Cognitive deficits are often associated with Parkinson’s disease (PD), although their prevalence in PD patients without dementia is still unknown. In order to describe the neuropsychological profile of PD patients without dementia, a sample of 103 PD patients was compared with a control group consisting of 38 healthy elderly subjects. Psychometric assessment consisted of the Mini Mental State Examination, the Dementia Rating Scale and a battery of neuropsychological tests. The Beck Depression Inventory was used to assess depression in PD patients. Dementia was diagnosed in 27 patients. Among non-demented subjects, 34 (45%) had no cognitive impairment and 42 (55%) had a mild cognitive impairment. Subjects with mild cognitive impairment were older, had a later onset of the disease, and more severe motor symptoms than cognitively intact subjects. Identification of mild cognitive impairment is important, since these symptoms are important for patient management and may also facilitate to determine prognosis.

Objective: To study mortality in subjects with mild dementia in Norway with a special focus on patients with Lewy body dementia (LBD) compared to Alzheimer's disease (AD). Methods: All referrals of mild dementia patients to dementia clinics in western Norway from March 2005 to March 2007 were included and followed until December 2012. Diagnoses were based on a comprehensive standardized assessment program. Results: Of 209 patients, 137 (66%) had AD and 53 (25%) had LBD. Dementia was associated with increased mortality (standardized mortality ratio = 1.8, AD 1.5, LBD 2.6). The median survival time was 6.2 years (95% CI 5.4-6.9). Predictors of mortality were age at diagnosis (HR 1.1 per year) and LBD diagnosis (HR 2.4). Conclusion: Dementia patients had an increased mortality, particularly those with LBD.

To compare neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and dementia with Lewy bodies(DLB).Neuropsychiatric symptoms and caregiver distress were assessed using the Neuropsychiatric Inventory (NPI) in mild DLB (n = 57) and AD (n = 126), and compared across the two groups using non-parametric tests.The DLB patients had a higher NPI totalscore (median 24 vs. 11.5, p0.005), more numerous symptoms (median 5 vs. 4, p = 0.001) and more clinically significant symptoms (3 vs. 1, p = 0.001). They also had higher item hallucinations (6 vs. 2, p0.005) and apathy (7 vs. 5, p = 0.002) subscores. Caregivers scored higher on the NPI total caregiver distress scale (12.5 vs. 6, p = 0.003).In mild dementia, DLB patients have more neuropsychiatric symptoms and more associated caregiver distress compared with AD.

Objectives: To explore how the core and suggestive symptoms of dementia with Lewy bodies (DLB) cluster in persons with newly diagnosed mild dementia, and whether they are associated with a particular pattern of cognitive impairment. Method: Persons with mild dementia (n = 139) were recruited from dementia clinics in western Norway. Symptoms were rated using standardized instruments. A 2-step cluster analysis was applied to classify persons into groups according to scores on scales for hallucinations, parkinsonism, fluctuations and REM sleep behaviour disorder (RBD). Result: Four distinct clusters were revealed: a ‘Lewy body dementia’ (LBD) cluster with high scores for hallucinations, parkinsonism and fluctuation, and a ‘non-LBD’ cluster with low scores on all DLB symptom scales. In addition, 2 clusters with high scores on either RBD or cognitive fluctuation scales emerged. Persons in the LBD cluster had lower scores for visuospatial cognitive abilities as compared to the non-LBD group (p = 0.002). Conclusion: Applying cluster analysis, we identified distinct subgroups in mild dementia based on symptoms such as hallucinations, parkinsonism and cognitive fluctuations. Our findings provide empirical support for diagnosing DLB. Visual hallucinations and motor parkinsonism might be the most distinguishing symptoms for DLB in mild dementia.

Background/Aims: Orthostatic hypotension (OH) and QTc prolongation have potentially important prognostic and therapeutic consequences but have rarely been studied in patients with mild dementia. Methods: Patients with mild dementia were diagnosed according to consensus criteria after comprehensive standardized assessment. OH and QTc were assessed using standardized criteria. Results: OH was significantly more common in the dementia than in the control group, and systolic drop was higher in those with dementia with Lewy bodies. There were no significant differences in QTc values between dementia and control subjects. Conclusion: OH occurs even in patients with mild dementia, in particular in dementia with Lewy bodies. QTc was not prolonged in patients with mild dementia compared with normal controls.

Background: The aim of this study was to explore the relationship between cerebrospinal fluid biomarkers and neuropsychiatric symptoms in people with Alzheimer’s disease. Psychosis, agitation, apathy and depression were assessed using standardised measures in 32 patients with mild Alzheimer’s disease. Methods: The levels of the 42-amino-acid form of β-amyloid (Aβ1–42), tau and p-tau (phosphorylated at threonine 181) were quantified using the conventional enzyme-linked immunosorbent assay method. Results: Our result shows that apathy is significantly correlated with tau and p-tau but not with Aβ1–42. There were no significant correlations between indices of psychosis/agitation,or depression and cerebrospinal fluid Aβ1–42, tau or p-tau concentrations. Conclusion: Our finding suggests that apathy is associated with the level of neurofibrillary tangles in people with mild Alzheimer’s disease. In contrast, the overall levels of neurofibrillary tangles or amyloid plaques do not seem to be associated with depression or psychosis, indicating that other brain changes contribute to these symptoms.

The clinical diagnostic criteria for dementia with Lewy bodies (DLB) have a low sensitivity, and there are no generally accepted biomarkers to distinguish DLB from other dementias. Our aim was to identify biomarkers that may differentiate DLB from Alzheimer's disease (AD).We performed a systematic literature search for studies of EEG, imaging techniques and genetic and CSF markers that provide sensitivity and specificity in the identification of DLB.The best evidence was for scintigraphy of the striatal dopamine transporter system using FP-CIT SPECT. Several small scintigraphy studies of cardiovascular autonomic function using metaiodobenzylguanidine SPECT have reported promising results. Studies exploring innovative techniques based on CSF have reported interesting findings for the combination of amyloid beta (abeta) isoforms as well as alpha-synuclein, and there are interesting results emerging from preliminary studies applying proteomic techniques. Data from studies using structural MRI, perfusion SPECT, genetics and EEG studies show differences between DLB and AD but only at a group level.Several potential biomarkers for the differential diagnosis of probable DLB and AD have shown good diagnostic accuracy in the research setting. Data from large multicentre studies and from studies with autopsy confirmation exist for scintigraphy of the dopamine transporter system. Future studies should explore its value in possible DLB and for clinical management and health economics.

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are common clinical dementias characterized neuropathologically by the presence of cortical Lewy body pathology and with distinct clinical and neurobiological similarities. Importantly, genetic factors seem to play a key role in the pathogenesis of Parkinson's disease. In the current article, we examine the evidence for a genetic component to DLB and PDD by reviewing studies of familial PDD and DLB as well as familial coincidental PDD and DLB, and report the genes involved. There is a convincing genetic overlap between both syndromes, suggesting that they share a common etiological factor.