Time Perception in Prodromal Alzheimer's Dementia and in Prodromal Dementia With Lewy Bodies

Background: Time perception is a subjective experience or sense of time. Previous studies have shown that Alzheimer's dementia (AD) patients have time perception deficits compared to a cognitively unimpaired control group (CU). There are only a few studies on dementia with Lewy bodies (DLB) patients' time perception in comparison with CU and AD patients. Early intervention and prescription of the right medicine may delay the deterioration of AD and DLB, moreover, knowing how prodromal AD (prAD) and prodromal DLB's (prDLB) time perception differ from each other might be helpful for future understanding of these two dementias. Therefore, the purpose of this study is to explore the difference in time perception performance between prodromal AD and prodromal DLB.Methods: We invited people diagnosed with prAD, prDLB, and CU to participate in this study. Tests of verbal estimation of time and time interval production were used to assess their time perception. We analyzed the average time estimation (ATE), absolute error score (ABS), coefficient of variance (CV), and subjective temporal unit (STU) within the three groups.Results: A total of 40 prAD, 30 prDLB, and 47 CU completed the study. In the verbal estimation test, the CV for the prAD was higher than both prDLB and CU at the 9 s interval, and the CV of prAD was higher than CU at the 27 s interval. In the time interval production test, the subjective time units of prDLB were higher than prAD at the 10 s interval, while those of both prDLB and CU were higher than prAD at the 30 s interval. The percentage of subjects with STU < 1.0 s, indicating overestimation, was higher in prAD than both prDLB and CU.Conclusion: Time perception of prAD patients showed imprecision and overestimation of time, while prDLB tended to underestimate time intervals. No significant difference was found in accuracy among the three groups. It is speculated that the clinical and pathological severity of the two prodromal dementia stages may be different, and some patients have not yet had their time perception affected.

Prodromal Dementia With Lewy Bodies: Evolution of Symptoms and Predictors of Dementia Onset

Background: Research criteria for prodromal dementia with Lewy bodies (DLB) were published in 2020, but little is known regarding prodromal DLB in clinical settings. Methods: We identified non-demented participants without neurodegenerative disease from the National Alzheimer’s Coordinating Center Uniform Data Set who converted to DLB at a subsequent visit. Prevalence of neuropsychiatric and motor symptoms were examined up to 5 years prior to DLB diagnosis. Results: The sample included 116 participants clinically diagnosed with DLB and 348 age and sex-matched (1:3) Healthy Controls. Motor slowing was present in approximately 70% of participants 3 years prior to DLB diagnosis. In the prodromal phase, 50% of DLB participants demonstrated gait disorder, 70% had rigidity, 20% endorsed visual hallucinations, and over 50% of participants endorsed REM sleep behavior disorder. Apathy, depression, and anxiety were common prodromal neuropsychiatric symptoms. The presence of 1+ core clinical features of DLB in combination with apathy, depression, or anxiety resulted in the greatest AUC (0.815; 95% CI: 0.767, 0.865) for distinguishing HC from prodromal DLB 1 year prior to diagnosis. The presence of 2+ core clinical features was also accurate in differentiating between groups (AUC = 0.806; 95% CI: 0.756, 0.855). Conclusion: A wide range of motor, neuropsychiatric and other core clinical symptoms are common in prodromal DLB. A combination of core clinical features, neuropsychiatric symptoms and cognitive impairment can accurately differentiate DLB from normal aging prior to dementia onset.

Prospective Metamemory Monitoring of Episodic Visual Memory in Community-Dwelling Older Adults with Subjective Cognitive Decline and Mild Cognitive Impairment

Objective Metamemory tasks have been utilized to investigate anosognosia in older adults with dementia, though previous research has not systematically compared memory self-awareness in prodromal dementia groups. This represents an important oversight given that remedial and interventional efforts may be most beneficial before individuals’ transition to clinical dementia. We examine differences in memory self-awareness and memory self-monitoring between cognitively healthy elderly controls and prodromal dementia groups. Methods Participants with subjective cognitive decline despite intact objective neuropsychological functioning (SCD; n = 82), amnestic mild cognitive impairment (aMCI; n = 18), nonamnestic mild cognitive impairment (naMCI; n = 38), and normal cognitive functioning (HC; n = 120) were recruited from the Einstein Aging Study for a cross-sectional study. Participants completed an experimental visual memory-based global metamemory prediction task and subjective assessments of memory/cognition and self-awareness. Results While, relative to HC, memory self-awareness and memory self-monitoring were preserved for delayed memory performance in SCD and aMCI, these processes were impaired in naMCI. Furthermore, results suggest that poor metamemory accuracy captured by our experimental task can be generalized to everyday memory problems. Conclusions Within the framework of the Cognitive Awareness Model, our findings provide preliminary evidence that poor memory self-awareness/self-monitoring in naMCI may reflect an executive or primary anosognosia, with implications for tailored rehabilitative interventions.

Neuropsychiatric Symptoms of Alzheimer’s Disease in Down Syndrome and Its Impact on Caregiver Distress

Background: Neuropsychiatric symptoms (NPS) are non-cognitive manifestations common to dementia and other medical conditions, with important consequences for the patient, caregivers, and society. Studies investigating NPS in individuals with Down syndrome (DS) and dementia are scarce. Objective: Characterize NPS and caregiver distress among adults with DS using the Neuropsychiatric Inventory (NPI). Methods: We evaluated 92 individuals with DS (≥30 years of age), divided by clinical diagnosis: stable cognition, prodromal dementia, and AD. Diagnosis was determined by a psychiatrist using the Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS). NPS and caregiver distress were evaluated by an independent psychiatrist using the NPI, and participants underwent a neuropsychological assessment with Cambridge Cognitive Examination (CAMCOG-DS). Results: Symptom severity differed between-groups for delusion, agitation, apathy, aberrant motor behavior, nighttime behavior disturbance, and total NPI scores, with NPS total score being found to be a predictor of AD in comparison to stable cognition (OR for one-point increase in the NPI = 1.342, p = 0.012). Agitation, apathy, nighttime behavior disturbances, and total NPI were associated with CAMCOG-DS, and 62% of caregivers of individuals with AD reported severe distress related to NPS. Caregiver distress was most impacted by symptoms of apathy followed by nighttime behavior, appetite/eating abnormalities, anxiety, irritability, disinhibition, and depression (R2 = 0.627, F(15,76) = 8.510, p < 0.001). Conclusion: NPS are frequent and severe in individuals with DS and AD, contributing to caregiver distress. NPS in DS must be considered of critical relevance demanding management and treatment. Further studies are warranted to understand the biological underpinnings of such symptoms.

Locus Coeruleus Malfunction Is Linked to Psychopathology in Prodromal Dementia With Lewy Bodies

Background: The locus coeruleus (LC) is a nucleus in the human brainstem with a variety of noradrenaline-driven functions involved in cognition, emotions, and perception. Dementia with Lewy bodies (DLB) constitutes a neurodegenerative disease involving deposits of alpha-synuclein, first appearing in the brainstem. The goal of this narrative review is to delineate the relationship between the expression of psychiatric symptoms as an early-onset of DLB and the degeneration of the LC's noradrenaline system.Methods: We searched in PubMed for relevant articles concerning LC degeneration and psychiatric symptoms in prodromal DLB in this narrative review. We rely on the McKeith criteria for prodromal psychiatric DLB.Results: We found four studies that document neuronal loss, deposits of Lewy bodies and other hints for neurodegeneration in the LC in patients with DLB. Furthermore, we reviewed theories and studies on how the degenerated noradrenaline LC system contributes to psychiatric DLB's phenotype. We hypothesized how anxiety, hallucinations, delusions, and depressive symptoms might occur in DLB patients due to degenerated noradrenergic neurons entailing consecutive altered noradrenergic transmission in the LC's projection areas.Conclusions: LC degeneration in prodromal DLB might cause psychiatric symptoms as the first and non-motor manifestation of DLB, as the LC is affected earlier by degeneration than are dopaminergic structures such as the substantia nigra, which are impaired later in the disease course.

2D Virtual Reality-Based Exercise Improves Spatial Navigation in Institutionalized Non-robust Older Persons: A Preliminary Data Report of a Single-Blind, Randomized, and Controlled Study

Background: Spatial navigation is a prodromal dementia marker. Exercise used alongside virtual reality improves many cognitive functions, but effects on spatial navigation are still unclear.Objective: To investigate the effect of virtual reality-based physical exercise with 2D exergames on spatial navigation in institutionalized non-robust older persons.Method: A total of 14 older persons (aged ≧ 60) were randomly allocated to the exergame (EG) and active control (ACG) groups. EG performed exercises with 2D exergames, while the ACG used the same movements as the EG, but without the use of virtual reality. Spatial navigation was assessed through the Floor Maze Test, where the immediate maze time (IMT) and delayed maze time (DMT) were recorded.Results: Spatial navigation was enhanced in EG participants compared to ACG individuals. A significant (p = 0.01) IMT reduction between groups was observed, while DMT time without prior planning was significantly different at the significance threshold (p = 0.07).Conclusions: Virtual reality-based exercise improves the spatial navigation of institutionalized non-robust older persons. This study should be replicated to confirm the findings reported herein.Clinical Trial Registration: This study was registered in the Brazilian Registry of Clinical Trials (Protocol RBR-8dv3kg - https://ensaiosclinicos.gov.br/rg/RBR-8dv3kg).