Prodromal Stage Of Dementia Research Articles

APOE4 and Confluent White Matter Hyperintensities Have a Synergistic Effect on Episodic Memory Impairment in Prodromal Dementia.

White matter hyperintensities (WMH) are a known risk factor for cognitive decline. While the ɛ4 allele of apolipoprotein E gene (APOE4) is another risk factor for cognitive decline, it remains unclear how APOE4 affects the relationship between WMH and cognitive decline, specifically in the prodromal stage of dementia. To determine how APOE4 moderates the relationship between WMH and cognition in prodromal dementia. Two-hundred-sixteen participants with prodromal dementia underwent magnetic resonance imaging (MRI), neuropsychological testing (global and domain wise), cardiovascular risk factor assessments, and APOE genotyping. Visual ratings for WMH as well as total and lobar WMH volumes were quantified. Moderation analysis was performed to determine the influence of APOE4 on the relationship between WMH and performance on global and domain-specific cognitive measures. The role of confluent and non-confluent WMH on cognition was additionally studied using logistic regression. APOE4 carriers (n = 49) had poorer memory and higher global WMH (10.01 mL versus 6.23 mL, p = 0.04), temporal WMH (1.17 mL versus 0.58 mL, p = 0.01), and occipital WMH (0.38mL versus 0.22 mL, p = 0.02) compared to APOE4 non-carriers (n = 167). Moderation analysis revealed that APOE4 positivity strengthened the relationship between higher global as well as lobar WMH burden and poorer episodic memory. Furthermore, APOE4 carriers with confluent WMH were 4.81 times more likely to have impaired episodic memory compared to non-confluent WMH and non-APOE carriers. The impact of WMH on memory may be strongest among APOE4 carriers. Clinicians targeting WMH would need to consider the APOE4 allele and WMH severity status to strategize cognitive interventions.

Hand movements in Mild Cognitive Impairment: clinical implications and insights for future research.

Decreased upper-extremity/visuomotor abilities are frequently encountered in healthy aging. However, few studies have assessed hand movements in the prodromal stage of dementia. The evaluation of visuomotor skills in patients with Mild Cognitive Impairment (PwMCI) may have non-negligible clinical relevance both in diagnostic and prognostic terms, given the strong relationships with executive functioning and functional autonomies. In the present review paper, these issues will be disclosed by describing general pathophysiological and neuropsychological mechanisms responsible for visuomotor deficits, and by reporting the available experimental results on differences in visuomotor functioning between PwMCI, healthy controls and/or patients with dementia. Moreover, the relationships binding visuomotor and executive domains to functional autonomies will be then addressed. Finally, we will propose insights for future research.

Automatic screening of mild cognitive impairment and Alzheimer’s disease by means of posterior-thresholding hesitation representation

Dementia is a chronic or progressive clinical syndrome, characterized by the deterioration of problem-solving skills, memory and language. In Mild Cognitive Impairment (MCI), which is often considered to be the prodromal stage of dementia, there is also a subtle deterioration of these cognitive functions; however, it does not affect the patients’ ability to carry out simple everyday activities. The timely identification of MCI could provide more effective therapeutic interventions to delay progression, and to postpone the possible conversion to dementia. Since language changes in MCI are present even before the manifestation of other distinctive cognitive symptoms, a non-invasive way of early automatic screening could be the use of speech analysis. Earlier, our research team developed a set of temporal speech parameters that mainly focus on the amount of silence and hesitation, and demonstrated its applicability for MCI detection. However, for the automatic extraction of these attributes, the execution of a full Automatic Speech Recognition (ASR) process is necessary. In this study we propose a simpler feature extraction approach, which still quantifies the amount of silence and hesitation in the speech of the subject, but does not require the application of a full ASR system. We experimentally demonstrate that this approach, operating directly on the frame-level output of a HMM/DNN hybrid acoustic model, is capable of extracting attributes as useful as the ASR-based temporal parameter extraction workflow was able to. That is, on our corpus consisting of 25 healthy controls, 25 MCI and 25 mild AD subjects, we achieve a (three-class) classification accuracy of 70.7%, an F-measure score of 89.6 and a mean AUC score of 0.804. We also show that this approach can be applied on simpler, context-independent acoustic states with only a slight degradation of MCI and mild Alzheimer’s detection performance. Lastly, we investigate the usefulness of the three speaker tasks which are present in our recording protocol.

Longitudinal atrophy in prodromal dementia with Lewy bodies points to cholinergic degeneration.

Mild cognitive impairment with the core clinical features of dementia with Lewy bodies is recognized as a prodromal stage of dementia with Lewy bodies. Although grey matter atrophy has been demonstrated in prodromal dementia with Lewy bodies, longitudinal rates of atrophy during progression to probable dementia with Lewy bodies are unknown. We investigated the regional patterns of cross-sectional and longitudinal rates of grey matter atrophy in prodromal dementia with Lewy bodies, including those who progressed to probable dementia with Lewy bodies. Patients with mild cognitive impairment with at least one core clinical feature of dementia with Lewy bodies (mean age = 70.5; 95% male), who were enrolled in the Mayo Clinic Alzheimer’s Disease Research Center and followed for at least two clinical evaluations and MRI examinations, were included (n = 56). A cognitively unimpaired control group (n = 112) was matched 2:1 to the patients with mild cognitive impairment by age and sex. Patients either remained stable (n = 28) or progressed to probable dementia with Lewy bodies (n = 28) during a similar follow-up period and pathologic confirmation was available in a subset of cases (n = 18). Cross-sectional and longitudinal rates of grey matter atrophy were assessed using voxel-based and atlas-based region of interest analyses. At baseline, prodromal dementia with Lewy bodies was characterized by atrophy in the nucleus basalis of Meynert both in those who remained stable and those who progressed to probable dementia with Lewy bodies (P < 0.05 false discovery rate corrected). Increase in longitudinal grey matter atrophy rates were widespread, with greatest rates of atrophy observed in the enthorhinal and parahippocampal cortices, temporoparietal association cortices, thalamus and the basal ganglia, in mild cognitive impairment patients who progressed to probable dementia with Lewy bodies at follow-up (P < 0.05 false discovery rate corrected). Rates of inferior temporal atrophy were associated with greater rates of worsening on the clinical dementia rating–sum of boxes. Seventeen of the 18 (94%) autopsied cases had Lewy body disease. Results show that atrophy in the nucleus basalis of Meynert is a feature of prodromal dementia with Lewy bodies regardless of proximity to progression to probable dementia with Lewy bodies. Longitudinally, grey matter atrophy progresses in regions with significant cholinergic innervation, in alignment with clinical disease progression, with widespread and accelerated rates of atrophy in patients who progress to probable dementia with Lewy bodies. Given the prominent neurodegeneration in the cholinergic system, patients with prodromal dementia with Lewy bodies may be candidates for cholinesterase inhibitor treatment.

Cognitive reawakening and improved quality of life achieved after discontinuing 16 years of anti-seizure treatment with topiramate

ABSTRACT A 42-year-old female patient with epilepsy and a co-morbid migraine suffered from the severe cognitive side effects of topiramate (TPM) for more than 16 years with detrimental consequences for her daily functioning, career, and social interaction. Even a prodromal stage of dementia was suggested, giving rise to fears of developing a neurodegenerative disease. Recently, cognitive monitoring of attention and executive function before and after withdrawal of TPM revealed a significant recovery from the severe negative cognitive side effects of the long-standing and inefficacious antiseizure medication (ASM). Whereas the side effects were reversible after cessation, their consequences for the patient`s biography were permanent. A considerable increase in quality of life, however, was observed without TPM and family members were impressed by the improvements. This case illustrates the potentially severe consequences of negative cognitive side effects which affect daily functioning, career and social life, thus underscoring the importance of being knowledgeable of the potential cognitive risks when prescribing an ASM. Because cognitive side effects may not depend solely on ASM choice and drug load, but also on individual idiosyncratic intolerances, and patients might stay on their treatment for many years, cognitive monitoring is highly recommended.

Cortical network modularity changes along the course of frontotemporal and Alzheimer's dementing diseases

Cortical network modularity underpins cognitive functions, so we hypothesized its progressive derangement along the course of frontotemporal (FTD) and Alzheimer's (AD) dementing diseases. EEG was recorded in 18 FTD, 18 AD, and 20 healthy controls (HC). In the FTD and AD patients, the EEG recordings were performed at the prodromal stage of dementia, at the onset of dementia, and three years after the onset of dementia. HC underwent three EEG recordings at 2–3-year time interval. Information flows underlying EEG activity recorded at electrode pairs were estimated by means of Mutual Information (MI) analysis. The functional organization of the cortical network was modelled by means of the Graph theory analysis on MI adjacency matrices. Graph theory analysis showed that the main hub of HC (Parietal area) was lost in FTD patients at onset of dementia, substituted by provincial hubs in frontal leads. No changes in global network organization were found in AD. Despite a progressive cognitive impairment during the FTD and AD progression, only the FTD patients showed a derangement in the cortical network modularity, possibly due to dysfunctions in frontal functional connectivity.

Psychotic Features Among Patients in the Prodromal Stage of Dementia with Lewy Bodies During Longitudinal Observation.

Many cases of dementia with Lewy bodies (DLB) present with various psychotic features, including hallucinations, depression, catatonia, and delusions before the onset of cognitive impairment. However, the characteristic features of these psychotic symptoms in prodromal DLB have not been sufficiently described. To clarify and describe the psychotic features of prodromal DLB before overt cognitive impairment. The authors analyzed the characteristic psychotic features of prodromal DLB in 21 subjects who developed severe psychotic symptoms without dementia and were diagnosed as DLB after the longitudinal observation period. They were then confirmed to have DLB through indicative and supportive biomarkers of scintigraphy. The psychotic features included a wide variety of symptoms, but convergent to three principal categories: catatonia, delusions-hallucinations, and depression and/or mania. Catatonia was observed in nine cases, five were delusional-hallucinatory, and seven were manic and/or depressive. Seven of the 21 cases exhibited delirium during longitudinal observation. A psychotic state repeatedly appeared without any trigger in 20 of the 21 patients. All subjects developed cognitive impairment at 9.1±4.6 (mean±SD) years after the initial appearance of psychotic symptoms, and subsequently diagnosed with DLB at 71.3±6.1 (mean±SD) years. Elderly patients with psychotic symptoms, such as catatonia, delusion-hallucination, manic and/or depressive features, and delirium without dementia, could indicate symptomatic psychosis or a prodromal stage of any neurocognitive disorder such as DLB. Therefore, further extensive workout (e.g., radioisotope neuroimaging) is required to avoid misdiagnosis.

Aberrant Topological Patterns of Structural Covariance Networks in Cognitively Normal Elderly Adults With Mild Behavioral Impairment.

Mild behavioral impairment (MBI), characterized by the late-life onset of sustained and meaningful neuropsychiatric symptoms, is increasingly recognized as a prodromal stage of dementia. However, the underlying neural mechanisms of MBI remain unclear. Here, we examined alterations in the topological organization of the structural covariance networks of patients with MBI (N = 32) compared with normal controls (N = 38). We found that the gray matter structural covariance networks of both the patients with MBI and controls exhibited a small-world topology evidenced by sigma value larger than one. The patients with MBI had significantly decreased clustering coefficients at several network densities and local efficiency at densities ranging from 0.05 to 0.26, indicating decreased local segregation. No significant differences in the characteristic path length, gamma value, sigma value, or global efficiency were detected. Locally, the patients with MBI showed significantly decreased nodal betweenness centrality in the left middle frontal gyrus, right inferior frontal gyrus (opercular part), and left Heschl gyrus and increased betweenness centrality in the left gyrus rectus, right insula, bilateral precuneus, and left thalamus. Moreover, the difference in the bilateral precuneus survived after correcting for multiple comparisons. In addition, a different number and distribution of hubs was identified in patients with MBI, showing more paralimbic hubs than observed in the normal controls. In conclusion, we revealed abnormal topological patterns of the structural covariance networks in patients with MBI and offer new insights into the network dysfunctional mechanisms of MBI.

Longitudinal associations between C-reactive protein and cognitive performance in normative cognitive ageing and dementia.

systemic inflammation appears to play an important role in the pathogenesis and expression of Alzheimer's disease and other dementias. Previous research has found that elevated levels of serum C-reactive protein (CRP) is associated with poorer cognitive functioning and increased risk for dementia. However, most studies are limited by single CRP measurements, which fail to capture long-term inflammatory exposures or dynamic changes in inflammation and cognition which may occur across repeated measurements. using data from 3,563 older adults aged 65-101 from the Health and Retirement Study, we examined bivariate changes in CRP and cognition measured repeatedly over a 10-year follow-up. Bivariate multilevel models estimated the effect of time-varying CRP on cognition among cognitively healthy older adults and in a subset of 427 participants who reported incident dementia onset during the follow-up period. in cognitively healthy participants, CRP was associated with lower level of cognitive functioning, but not rate of change over time. This effect was significant in participants under 80years of age (b = -0.09, standard error (SE) = 0.05, P = 0.04), but not in older participants. In participants with incident dementia, those with higher CRP experienced smaller rates of cognitive decline, leading up to dementia diagnosis. elevated levels of CRP predict poorer cognition and increased dementia risk in cognitively healthy adults under the age of 80. Conversely, increased CRP may confer protective effects on cognition in the prodromal stage of dementia.

Later life depression as risk factor for developing dementia: epidemiological evidence, predictive models, preventive strategies and future trends.

Current investigations in pre-symptomatic dementia have suggested that depressive mood, a treatable condition, may play an important role in the development of the disorder. However, whether depression in adulthood constitute a risk factor, or a prodrome of dementia remains unclear. A major implication in such dispute is the analytic framework used to identify putative risk factors. Indeed, if evaluated in the years immediately prior to dementia diagnosis the association between depression and dementia may reflect depressive symptoms as a prodrome of yet-undiagnosed dementia. Unfortunately, long term prospective cohort investigations, reaching back into the preclinical phase of dementia are sparse. Here, we have surveyed high-quality evidence (systematic reviews and meta-analyses) on the association between depressive symptoms and increased odds of dementia. Meta-analytic findings are also presented and discussed regarding depression as a prodromal stage of dementia, or a consequence of underlying neurodegenerative processes. Additionally, the potential confounding effect of several variables on the risk association between depression and dementia, an aspect hardly investigated, is discussed. While early onset late-life depression - defined as starting before 60 years of age - increases the odds of developing dementia in predisposed subjects, late-onset depression appears to be a prodrome and a clear accelerating factor for cognitive deterioration. Since it is increasingly important to consider the potential of preemptive approaches to decrease the impact of dementia, evidence on potentially effective preventive strategies targeting depression as a risk factor, and next steps in further research are presented as concluding remarks.

Cross-lingual detection of mild cognitive impairment based on temporal parameters of spontaneous speech

Mild Cognitive Impairment (MCI) is a heterogeneous clinical syndrome, often considered as the prodromal stage of dementia. It is characterized by the subtle deterioration of cognitive functions, including memory, executive functions and language. Mainly due to the tenuous nature of these impairments, a high percentage of MCI cases remain undetected. There is evidence that language changes in MCI are present even before the manifestation of other distinctive cognitive symptoms, which offers a chance for early recognition. A cheap non-invasive way of early screening could be the use of automatic speech analysis. Earlier, our research team developed a set of speech temporal parameters, and demonstrated its applicability for MCI detection. For the automatic extraction of these attributes, a Hungarian-language ASR system was employed to match the native language of the MCI and healthy control (HC) subjects. In practical applications, however, it would be convenient to use exactly the same tool, regardless of the language spoken by the subjects. In this study we show that our temporal parameter set, consisting of articulation rate, speech tempo and various other attributes describing the hesitation of the subject, can indeed be reliably extracted regardless of the language of the ASR system used. For this purpose, we performed experiments both on English-speaking and on Hungarian-speaking MCI patients and healthy control subjects, using English and Hungarian ASR systems in both cases. Our experimental results indicate that the language on which the ASR system was trained only slightly affects the MCI classification performance, because we got quite similar scores (67-92%) as we did in the monolingual cases (67-92% as well). As our last investigation, we compared the proposed attribute values for the same utterances, utilizing both the English and the Hungarian ASR models. We found that the articulation rate and speech tempo values calculated based on the two ASR models were highly correlated, and so were the attributes corresponding to silent pauses; however, noticeable differences were found regarding the filled pauses (still, these attributes remained indicative for both languages). Our further analysis revealed that this is probably due to a difference regarding the annotation of the English and the Hungarian ASR training utterances.

A history of cigarette smoking is associated with faster functional decline and reduction of entorhinal cortex volume in mild cognitive impairment.

Little is known about the longitudinal association of cigarette smoking with Alzheimer’s Disease (AD) related markers in subjects with mild cognitive impairment (MCI). In this study, we aimed to examine the effect of a history of cigarette smoking on change in global cognition, verbal memory, functional performance, hippocampal volume, entorhinal cortex volume, brain glucose metabolism, and CSF AD pathologies over time in MCI subjects. At baseline, there were 870 subjects with MCI, including 618 non-smokers (no history of smoking) and 252 smokers (any lifetime history of smoking). Linear mixed models were fitted for each outcome with adjustment of several covariates. The major findings were: (1) Among older people with MCI, smokers showed faster decline in functional performance compared to non-smokers; (2) Smokers demonstrated steeper decline in entorhinal cortex volume than non-smokers; (3) A history of cigarette smoking was not associated with change in CSF Aβ42, t-tau or p-tau levels over time in MCI subjects. In conclusion, we found that a history of cigarette smoking was associated with faster decline in functional performance and entorhinal cortex volume over time at the prodromal stage of dementia.

Deficits in saccadic eye movements differ between subtypes of patients with mild cognitive impairment

ABSTRACT Introduction: Mild cognitive impairment (MCI) is known to be heterogeneous in its cognitive features and course of progression. Whilst memory impairment is characteristic of amnestic MCI (aMCI), cognitive deficits other than memory can occur in both aMCI and non-amnestic MCI (naMCI) and accurate assessment of the subtypes of MCI is difficult for clinicians without the application of extensive neuropsychological testing. In this study, we examine metrics derived from recording of reflexive and voluntary saccadic eye movements as a potential alternative method for discriminating between subtypes and assessing cognitive functions in MCI. Method: A total of 29 MCI patients and 29 age- and education-matched healthy controls (HCs) participated in the cross-sectional study. We recorded horizonta l and vertical pro-saccades and anti-saccade responses. All the participants also completed a comprehensive neuropsychological tests battery. Results: Significant differences in saccadic eye movement were found between the subtypes of MCI and HCs. Patients with aMCI had a higher percentage of short latency “express” saccades than HCs. We found strong associations between saccadic reaction times and cognitive domains, including executive functions and attention. The mini-mental state examination (MMSE) was also found to correlate with uncorrected errors in the anti-saccade task. Conclusions: The increased proportion of saccades in the express latency range in aMCI may be indicative of problems with cognitive inhibitory control in these patients. A focus on this and other saccade metrics in the preclinical and prodromal stages of dementia may help to predict the clinical progression of the disease and direct interventions for the management of MCI. The clinical significance of saccadic eye movement impairments in MCI is not yet fully understood and should be investigated in further studies using larger samples.

Cardiovascular Health, Functional Disability, and Leisure Activities Profiles in Relation to Mental Aging

We investigated cardiovascular health, functional disability and leisure activities profiles independently and in relation to cognitive decline and dementia in high and low-medium income countries using data from the English Longitudinal Study of Ageing, Irish Longitudinal Study on Ageing and Brazilian Bambui Cohort Study of Aging. Functional loss among older Brazilians has shown a hierarchical sequence over the 15-year follow-up, with the highest incidence in functional disability reported for dressing, followed by getting out of bed, bathing/showering, walking across a room, using the toilet and eating (de Oliveira). Using the Life’s Simple 7, an ideal cardiovascular health scoring system evaluating the muscular strength, mobility and physiological stress, we showed a reliable prediction of cognitive trajectories in a representative sample of Irish individuals (De Looze). Within the same cohort, we report discrepancies between men and women in functional decline driven by domestic tasks, rather than determining differential cognitive trajectories (McGarrigle). In an English representative sample, we found that participants with an increasing number of functional impairments over almost a decade were more likely to be classified with subsequent dementia compared with those with no impairments and this may imply a more comprehensive ascertainment during the prodromal stage of dementia (Cadar). In contrast, a reduced risk of dementia was found for individuals with higher levels of engagement in cognitively stimulating activities, that may preserve cognitive reserve until later in life (Almeida). Identifying factors that influence cognitive aging and dementia risk in a multifactorial perspective is critical toward developing adequate intervention and treatment.

Functional Impairments and Dementia Incidence in the English Longitudinal Study of Ageing

Functional disability might be related to an increased risk of dementia or could represent a prodromal stage. We examined the occurrence of functional impairments over eight years follow-up and their association with dementia incidence in 1,666 participants aged 65+ from the English Longitudinal Study of Ageing. Growth models with distal outcome were used to examine whether different trajectories of functional abilities (activities of daily living (ADL); and instrumental activities of daily living (IADL)) between 2002/03 and 2010/11, were associated with dementia incidence four years later (2014/15). Participants with an increasing number of functional impairments (Class III), were more likely to be classified with subsequent dementia compared with those with no impairments (Class I). An increased risk was also observed for individuals with raised levels of impairments (Class II). We found IADLs more sensitive than ADLs, and this may imply a more comprehensive ascertainment during the prodromal stage of dementia.

Prevalence and severity of neuropsychiatric symptoms in the prodromal stages of dementia with Lewy bodies and Alzheimer’s disease

AbstractBackgroundThere has been minimal investigation into the prodromal features dementia with Lewy bodies (DLB) and how they may differ from prodromal features of Alzheimer’s disease (AD).MethodThe data analyzed for this investigation were collected as part of a large, prospective longitudinal study conducted by the National Alzheimer’s Coordinating Center (NACC database is funded by NIA/NIH Grant U01 AG016976). We identified 110 non‐demented participants who converted to DLB at a subsequent visit. Participants were age and sex matched to 220 non‐demented participants who later converted to AD. We examined between group differences in the prevalence of symptoms on the Neuropsychiatric Inventory Questionnaire (NPI‐Q) at time of dementia diagnosis and in the 1‐3 years preceding conversion to dementia using Chi‐Square or Fisher Exact Test analyses.ResultsFor the DLB and AD groups, 82% were male and the average age at the time of dementia diagnosis was 75.4 years (SD=7.9). There was no significant difference in education between the two groups. The DLB group was significantly less culturally diverse than the AD group (See Table 1). Nighttime behaviors and hallucinations were significantly more common in the DLB group compared to the AD group at all time points during the prodromal phase and at the time of dementia diagnosis. There was no significant difference in the informant’s report of motor symptoms in the prodromal phases between the two groups (See Table 2).ConclusionThe DLB group demonstrated a significantly higher prevalence of nighttime behaviors and hallucinations than the AD group in both the prodromal phase and at the time of dementia diagnosis. These findings support the occurrence of core clinical features of DLB during the prodromal phase of the disease [1]; however, there was no significant difference in the informant’s report of motor symptoms within the prodromal phases, which warrants a comparison utilizing more objective motor data. Reference: 1. McKeith IG, Boeve BF, Dickson DW, et al.; Dementia with Lewy Bodies Consortium. Diagnosis and management of Dementia with Lewy Bodies: Fourth consensus report of the DLB Consortium. Neurol. 2017;89:1‐13.

PIH8 Primary Care Costs Due to Prodromal Alzheimer Disease: A Real-World Study in Patients with 10-Year or Longer Medical History

Little is known about the costs associated with the prodromal stages of dementia. The aim of this study is to estimate primary care costs triggered by Alzheimer disease (AD) prodromal signs and/or symptoms, during a 10-year or longer period preceding AD diagnosis, and compared them with costs cumulated in general population for the same signs and/or symptoms. This is a cohort study with a nested case-control analysis involving 1889 AD cases and 18890 controls aged 60 years or older, gathered from the Health Search Database (HSD), an Italian data source collecting primary care data. AD incident cases have been defined in accordance with ICD-9CM codes. Costs related to pharmacological treatment, diagnostic tests and specialist referrals triggered by prodromal AD signs and/or symptoms have been quantified and compared with costs cumulated by the same conditions in the general population aged 60 years or older In primary care patients developing AD, during the pre-diagnosis 10-year or longer period, prodromal signs and symptoms trigger diagnostic and therapeutic costs that are 55% significantly higher than those cumulated in general population for the same clinical reasons. After accounting for patients’ comorbidity burden and regional differences, the mean cost related to diagnostic and therapeutic procedures, and those related to specialist referrals, amounted to 854.1 € (SD: 630.6 €) in AD incident cases vs. 527.3 € (SD: 446.2) in control cases. Prodromal AD manifestations are associated to primary care costs that resulted higher than those cumulated in the general population aged 60 years or older for the same clinical reasons. A better interpretation of such signs and symptoms might aid GPs to set more precise and timely diagnostic pathways, as well as health care systems to optimize resource allocation when planning prevention and care paths for people at risk of cognitive decline.

Neuropsychological and biochemical features of cognitive resilient octogenarians and nonagenarians

AbstractBackgroundAlzheimer’s dementia has evolved into a biological construct based on fluid and imaging biomarkers to aid in early diagnosis. Biomarkers are expensive and not widely available. It is therefore important to define signatures of cognitive resiliency to better identify this group in the prodromal stages of dementia. Our AIM was to determine neuropsychological and biochemical characteristics of cognitively intact patients older than age 80.MethodSingle center, cross‐sectional study involving forty patients older than 80, admitted to a community hospital. Participants with diagnoses of dementia, delirium, history of falls, dependency on cognitively focused IADL, and those residing in residential care were excluded. Recruited patients were subjected to neurocognitive evaluation, with emphasis on episodic/working memory, semantic cognition, and visuoperceptual/executive spheres, using the Rey‐Osterrieth figure copy/recall (ROSC) test. Regression analysis was used to establish correlation.ResultThe mean age was 85 years (SD 4.06). The mean level of education was 12.12 years (SD 2.93). Only 28% of participants lived alone. Semantic evaluation was the most difficult task, with only 48% of patients able to pass. Patients who answered 3 memory tasks right, had a mean score of 21 (SD 4.6) on the ROSC recall. Those who pass 2 memory tasks, had a mean score of 18.75 (SD 5.20) on the ROSC recall, and those who pass only one, or failed all of them, had a mean score of 9. We identified the ROSC recall as the most powerful predictor of cognitive resiliency. Age correlated well with ROSC recall (p 0.0017, CI 45‐126), but no years of education (p 0.21, CI 2.32‐21). Hemoglobin had a significant effect on ROSC copy (p 0.0019, CI 5‐26), but no ROSC recall (p 0.84, CI ‐14‐12). No correlation was found between ROSC recall and MCV, RDW, or albumin level.ConclusionWe corroborate that age is the single most important factor for cognitive decay, whereas a normal hemoglobin level appears to be protective. Level of education seems to lose its protective effect in the old‐old and oldest‐old population. Patients able to perform well on the three types of memory, showed great proficiency on the ROSC recall.

Association of Late Life Depression, (Non-) Modifiable Risk and Protective Factors with Dementia and Alzheimer's Disease: Literature Review on Current Evidences, Preventive Interventions and Possible Future Trends in Prevention and Treatment of Dementia.

The number of people living with dementia and Alzheimer’s disease is growing rapidly, making dementia one of the biggest challenges for this century. Many studies have indicated that depression plays an important role in development of dementia, including Alzheimer’s disease; depression, especially, during the late life may either increase the risk of dementia or even being its prodromal stage. Despite a notably large number of carried observational studies and/or clinical trials, the association between the late life depression and dementia remains, due to the complexity of their relationship, still unclear. Moreover, during past two decades multiple other (non-)modifiable risk and possibly protective factors such as the hypertension, social engagement, obesity, level of education or physical (in)activity have been identified and their relationship with the risk for development of dementia and Alzheimer’s disease has been extensively studied. It has been proposed that to understand mechanisms of dementia and Alzheimer’s disease pathogeneses require their multifactorial nature represented by these multiple factors to be considered. In this review, we first summarize the recent literature findings on roles of the late life depression and the other known (non-)modifiable risk and possibly protective factors in development of dementia and Alzheimer’s disease. Then, we provide evidences supporting hypotheses that (i) depressive syndromes in late life may indicate the prodromal stage of dementia (Alzheimer’s disease) and, (ii) the interplay among the multiple (non-)modifiable risk and protective factors should be considered to gain a better understanding of dementia and Alzheimer’s disease pathogeneses. We also discuss the evidences of recently established interventions considered to prevent or delay the prodromes of dementia and provide the prospective future directions in prevention and treatment of dementia and Alzheimer’s disease using both the single-domain and multidomain interventions.

Hyperconnectivity in Dementia Is Early and Focal and Wanes with Progression.

We investigated in a longitudinal multicenter cohort study functional cortical connectivity changes along the course of frontotemporal dementia (FTD) and Alzheimer's disease (AD) from the prodromal stage of the diseases. Electroencephalography (EEG) was recorded in 18 FTD and 18 AD patients at the prodromal stage of dementia, at dementia onset, and 3years after dementia onset. Twenty healthy controls (HC) underwent EEG recordings at the same time interval as the patients. Mutual information (MI) analysis measured the strength of functional network connectivity. FTD and AD patients showed greater MI at the prodromal stage of dementia (FTD vs. HC P = 2 × 10-8; AD vs. HC P = 4 × 10-3). Local connectivity was higher in left and right frontal areas of FTD (P = 7 × 10-5 and 0.03) and in left and right posterior areas in AD (P = 3 × 10-5 and 5 × 10-5) versus HC. We showed cortical hyperconnectivity at the prodromal stage of dementia in areas involved in the specific pathological process of FTD (frontal regions) and AD (posterior regions). Hyperconnectivity disappeared during follow-up, thus suggesting that it is an early electrophysiological feature of dementia, potentially useful to identify prodromal FTD and AD.