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While much of the studies within the Uses and Gratifications (U&G) tradition were set to predict facets of media use, the current study examines how use motivations, nature of platform use, and privacy-related perceptions predict users' use continuance intentions for Facebook, Instagram, Twitter, and TikTok and their problematic use (i.e., addiction), simultaneously. The study uses a cross-sectional survey of undergraduate students at a large Midwestern University (N= 685), where participants expressed their motivations to use each of the four platforms (depending on their active use of the platform), platform affinity and other usage factors, their intentions to continue using the platform, and their problematic use of the platform. Findings showed superiority of Instagram in terms of U&G. Regression models highlighted differences in the four platforms' problematic use and continuance intentions. Findings are discussed within the framework of reconceptualizing U&G outcomes within the evolving social media environment. [ABSTRACT FROM AUTHOR]

Background: Young onset dementia is associated with a longer time to diagnosis compared to late onset dementia. Earlier publications have indicated that atypical presentation is a key contributing factor to the diagnostic delay. Our hypothesis was that even the most common presentation of Alzheimer's disease is associated with a substantial diagnostic delay in patients < 65 years.Objective: To determine the time to diagnosis, and time lags in the diagnostic pathway in typical young onset Alzheimer's disease in central Norway.Methods: The main sources of patients were the databases at the Department of Neurology, University Hospital of Trondheim (St. Olav's Hospital), and Department of Psychiatry, Levanger Hospital. Other sources included key persons in the communities, collaborating hospital departments examining patients with suspected cognitive impairment, and review of hospital records of all three hospitals in the area. Information on the time lags, and the clinical assessment, including the use of biomarkers, was collected from hospital notes. Caregivers were interviewed by telephone.Results: Time from first symptom to diagnosis in typical young onset Alzheimer's disease was 5.5 years (n = 223, SD 2.8). Time from onset to contact with healthcare services (usually a general practitioner) was 3.4 years (SD 2.3). Time from contact with healthcare services to the first visit at a hospital was 10.3 months (SD 15.5). Time from first visit at a hospital to diagnosis was 14.8 months (SD 22.6). The analysis of cerebrospinal fluid core biomarkers was performed after 8.3 months (SD 20.9).Conclusion: Typical Alzheimer's disease is associated with a substantial diagnostic delay in younger patients. Raising public awareness, and education of healthcare professionals on the aspects of young onset Alzheimer's disease is warranted. CSF core biomarkers should be performed earlier in the hospital evaluation process. [ABSTRACT FROM AUTHOR]

Abstract Background The objective of this study was to analyze factors influencing the risk and timing of Alzheimer's disease (AD) in central Norway. The APOE ε4 allele is the only consistently identified risk factor for late onset Alzheimer's disease (LOAD). We have described the allele frequencies of the apolipoprotein E gene (APOE) in a large population of patients with AD compared to the frequencies in a cognitively-normal control group, and estimated the effect of the APOE ε4 allele on the risk and the age at onset of AD in this population. Methods 376 patients diagnosed with AD and 561 cognitively-normal control individuals with no known first degree relatives with dementia were genotyped for the APOE alleles. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio for developing AD in different genotypes was calculated. Results Odds Ratio (OR) for developing AD was significantly increased in carriers of the APOE ε4 allele compared to individuals with the APOE ε3/ε3 genotype. Individuals carrying APOE ε4/ε4 had OR of 12.9 for developing AD, while carriers of APOE ε2/ε4 and APOE ε3/ε4 had OR of 3.2 and 4.2 respectively. The effect of the APOE ε4 allele was weaker with increasing age. Carrying the APOE ε2 allele showed no significant protective effect against AD and did not influence age at onset of the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from 78.4 years in patients without the APOE ε4 allele, to 75.3 in carriers of one APOE ε4 allele and 72.9 in carriers of two APOE ε4 alleles. Age at onset in early onset AD (EOAD) was not influenced by APOE ε4 alleles. Conclusion APOE ε4 is a very strong risk factor for AD in the population of central Norway, and lowers age at onset of LOAD significantly.

Abstract Background The main objective of this study was to investigate the angiotensin converting enzyme (ACE) genotype as a possible risk factor for migraine (both with and without aura) compared to controls. We also wanted to examine whether a clinical response to an ACE inhibitor, lisinopril, or an angiotensin II receptor blocker, candesartan, in migraine prophylaxis was related to ACE genotype. Methods 347 migraine patients aged 18–68 (155 migraine without aura (MoA), 187 migraine with aura (MwA) and 5 missing aura subgroup data) and 403 healthy non-migrainous controls > 40 years of age were included in the study. A polymerase chain reaction (PCR) was performed on the genomic DNA samples to obtain the ACE insertion (I)/deletion(D) polymorphisms. Results No significant differences between migraine patients and controls were found with regard to ACE genotype and allele distributions. Furthermore, there was no significant difference between the controls and the MwA or MoA subgroups. Conclusion In our sample there is no association between ACE genotype or allele frequency and migraine. In addition, ACE genotype in our experience did not predict the clinical response to lisinopril or candesartan used as migraine prophylactics.

Background: The epidemiology of young onset dementia is little researched compared to late onset dementia. Information on incidence rates is vital for medical professionals, and for government planning purposes.Objective: To determine the incidence of young onset dementia in a defined catchment area of central Norway.Methods: The target area was Trøndelag county in central Norway with a total population of 449,796 inhabitants per January 1, 2016. We applied multiple case ascertainment strategies with sources from both primary and secondary healthcare facilities. Included patients received a diagnosis of dementia according to DSM-IV in the ages 30 to 64 years during the years 2015-2017. Subtypes of dementia were diagnosed according to standardized criteria. Incidence rates for dementia and Alzheimer's disease with dementia were calculated according to age and sex.Results: A total of 89 incident cases were included. Incidence rates for dementia were 14.8 and 25.0 per 100,000 person-years for the age range 30-64 and 45-64, respectively. Corresponding incidence rates for Alzheimer's disease were 6.7 and 11.8. Alzheimer's disease represented half of all dementias. A majority of patients above the age of 50 had neurodegenerative disease, whereas non-degenerative disorders were more prevalent in younger patients.Conclusion: Young onset dementia is a significant contributor to the overall occurrence of dementia in central Norway, and Alzheimer's disease is by far the most common diagnosis. [ABSTRACT FROM AUTHOR]

Background: The unbiased amyloid, tau, and neurodegeneration (A/T/N) classification is designed to characterize individuals in the Alzheimer continuum and is currently little explored in clinical cohorts.Objective: A retrospective comparison of the A/T/N classification system with the results of a two-year clinical study, with extended follow-up up to 10 years after inclusion.Methods: Patients (n = 102) clinically diagnosed as Alzheimer's disease (AD) with dementia or amnestic mild cognitive impairment (MCI), and 61 cognitively healthy control individuals were included. Baseline cerebrospinal fluid core biomarkers for AD (Aβ42, phosphorylated tau, and total tau) were applied to the A/T/N classification using the final clinical diagnosis at extended follow-up as the gold standard.Results: A + T + N+ was a strong predictor for AD dementia, even among cognitively healthy individuals. Amnestic MCI was heterogenous, considering both clinical outcome and distribution within A/T/N. Some individuals with amnestic MCI progressed to clinical AD dementia within all four major A/T/N groups. The highest proportion of progression was among triple positive cases, but progression was also common in individuals with suspected non-Alzheimer pathophysiology (A-T + N+), and those with triple negative status. A-T-N- individuals who were cognitively healthy overwhelmingly remained cognitively intact over time, but in amnestic MCI the clinical outcome was heterogenous, including AD dementia, other dementias, and recovery.Conclusion: The A/T/N framework accentuates biomarkers over clinical status. However, when selecting individuals for research, a combination of the two may be necessary since the prognostic value of the A/T/N framework depends on clinical status. [ABSTRACT FROM AUTHOR]

The APOEɛ4 gene variant is the strongest genetic risk factor for Alzheimer's disease (AD), whereas APOEɛ3 conventionally is considered as 'risk neutral' although APOEɛ3-carriers also develop AD. Previous studies have shown that the apolipoprotein E3 (apoE3) isoform occurs as monomers, homodimers and heterodimers with apolipoprotein A-II in human body fluids and brain tissue, but the relevance of a plasma apoE3 monomer/dimer profile to AD is unknown. Here we assessed the distribution of monomers, homodimers and heterodimers in plasma from control subjects and patients with mild cognitive impairment (MCI) and AD with either a homozygous APOEɛ3 (n = 31 control subjects, and n = 14 MCI versus n = 5 AD patients) or APOEɛ4 genotype (n = 1 control subject, n = 21 MCI and n = 7 AD patients). Total plasma apoE levels were lower in APOEɛ4-carriers and overall correlated significantly to CSF Aβ42, p(Thr181)-tau and t-tau levels. Apolipoprotein E dimers were only observed in the APOEɛ3-carriers and associated with total plasma apoE levels, negatively correlated to apoE monomers, but were unrelated to plasma homocysteine levels. Importantly, the APOEɛ3-carrying AD patients versus controls exhibited a significant decrease in apoE homodimers (17.8±9.6% versus 26.7±6.3%, p = 0.025) paralleled by an increase in apoE monomers (67.8±18.3% versus 48.5±11.2%, p = 0.008). In the controls, apoE monomers and heterodimers were significantly associated with plasma triglycerides; the apoE heterodimers were also associated with levels of high-density lipoprotein cholesterol. The physiological relevance of apoE dimer formation needs to be further investigated, though the distribution of apoE in monomers and dimers appears to be of relevance to AD in APOEɛ3 subjects. [ABSTRACT FROM AUTHOR]

Background: Young onset dementia poses several challenges for the individual, health care, and society that are not normally relevant for late onset dementia, but is little researched.Objective: To determine the prevalence and subtypes of young onset dementia in a defined catchment area in central Norway.Methods: The main sources of patient identification were the databases at the Department of Neurology, University Hospital of Trondheim (St. Olav's Hospital), and Department of Psychiatry, Levanger Hospital. Both departments are the main sites for referral of young onset dementia (onset before age 65 years) in the county, covering approximately 90% of the catchment area of the study. Other sources included key persons in the communities, collaborating hospital departments examining dementia, and review of hospital records of all three hospitals in the area. Included patients met the DSM-IV criteria for dementia. The prevalence of dementias was calculated by sex and age.Results: All patients identified with dementia and onset before 65 years on census date were included in the study (n = 390). Patients younger than 65 on census date were included in the calculation of prevalence, giving a result of 76.3 per 100 000 persons at risk in the age category of 30-65 years, and 163.1 per 100,000 for the category 45-64 years. Etiology was heterogeneous, but the main subtype of dementia was Alzheimer's disease.Conclusions: Young onset dementia affects a significant number of people in central Norway. Prevalence figures are higher than previously reported from England and Japan, but are similar to a more recent study from Australia. [ABSTRACT FROM AUTHOR]

Purpose: The reports regarding the status of the immune system in patients with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) have been inconclusive. We approached this question by comparing a strictly defined group of CFS/ME outpatients to healthy control individuals, and thereafter studied cytokines in subgroups with various psychiatric symptoms. Materials and methods: Twenty patients diagnosed with CFS/ME according to the Fukuda criteria and 20 age- and sex-matched healthy controls were enrolled in the study. Plasma was analysed by ELISA for levels of the cytokines TNF-a, IL-4, IL-6 and IL-10. Participants also answered questionnaires regarding health in general, and psychiatric symptoms in detail. Results: Increased plasma levels of TNF-a in CFS/ME patients almost reached significance compared to healthy controls (p¼.056). When studying the CFS/ME and control groups separately, there was a significant correlation between TNF-a and The Hospital Anxiety and Depression Scale (HADS) depressive symptoms in controls only, not in the CFS/ME group. A correlation between IL-10 and psychoticism was found in both groups, whereas the correlation for somatisation was seen only in the CFS/ME group. When looking at the total population, there was a significant correlation between TNF-a and both the HADS depressive symptoms and the SCL-90-R cluster somatisation. Also, there was a significant association between IL-10 and the SCL-90-R cluster somatisation when analyzing the cohort (patients and controls together). Conclusions: These findings indicate that immune activity in CFS/ME patients deviates from that of healthy controls, which implies potential pathogenic mechanisms and possible therapeutic approaches to CFS/ME. More comprehensive studies should be carried out on defined CFS/ME subgroups. [ABSTRACT FROM AUTHOR]

Background: Kallikrein 6 (KLK6) is known to be an age-related protease expressed at high levels in the central nervous system. It was previously shown to be involved in proteolysis of extracellular proteins implicated in neurodegenerative diseases such as Alzheimer's disease (AD), prompting validation of KLK6 as a potential biomarker of disease. However, analyses of both plasma and cerebrospinal fluid (CSF) levels of KLK6 in patients with AD have been inconclusive. We present a detailed analysis of KLK6 in plasma and CSF in two separate cohorts in a cross-sectional and a longitudinal clinical setting. Methods: The cross-sectional cohort included control subjects without dementia and patients with AD, and the longitudinal cohort included patients with MCI and patients with AD followed over a 2-year period. Plasma and CSF levels of KLK6 were quantified by use of a previously developed and validated enzyme-linked immunosorbent assay. Statistical analyses were performed to compare KLK6 levels between diagnostic groups and to identify potential associations between KLK6 level, age, apolipoprotein E (APOE) genotype, total apoE level and the classical CSF AD biomarkers. Results: In the cross-sectional setting, KLK6 levels in plasma but not in CSF were significantly higher in the AD group than in control subjects. CSF but not plasma KLK6 levels were positively correlated with age in both the cross-sectional and longitudinal settings. In both cohorts, the CSF KLK6 levels were significantly and positively correlated with the CSF levels of core AD biomarkers. Total plasma and CSF apoE levels were positively associated with KLK6 in the crosssectional study. Finally, during the 2-year monitoring period of the longitudinal cohort, CSF KLK6 levels increased with disease progression over time in the investigated patient groups. Conclusions: In two separate cohorts we have confirmed the previously reported correlation between age and CSF levels of KLK6. Increased plasma KLK6 levels in patients with AD with a more advanced disease stage suggest KLK6 as a potential biomarker in patients with AD with more severe dementia. Significant correlations between KLK6 levels and core CSF AD biomarkers suggest molecular links between KLK6 and AD-related pathological processes. [ABSTRACT FROM AUTHOR]

Background: Amyloid beta 1-43 (Aβ43) may be a useful additional biomarker for diagnosing Alzheimer's disease (AD). We have investigated cerebrospinal fluid (CSF) levels of Aβ43 in patients with early-onset AD in contrast to levels in late-onset AD. For comparison, in addition to the 'core' biomarkers, several other analytes were also determined [YKL-40, neurofilament light (NF-L), glial fibrillary acidic protein (GFAP), and progranulin]. Material and Methods: Cerebrospinal fluid samples were obtained from patients with early-onset AD (age ≤ 62, = 66), late-onset AD (age ≥ 68, = 25), and groups of cognitively intact individuals (age ≤ 62, = 41, age ≥ 68, = 39). Core CSF AD biomarkers [amyloid beta 1-42 (Aβ42), total tau, phosphorylated tau] were analyzed, as well as levels of Aβ43 and other analytes, using commercially available enzyme-linked immunosorbent assays. Results: Cerebrospinal fluid Ab43 was significantly reduced in early-onset AD compared to late-onset AD (14.8 ± 7.3 vs. 21.8 ± 9.4 pg/ml, respectively), whereas the levels of Aβ42 in the two AD groups were not significantly different (474.9 ± 142.0 vs. 539.6 ± 159.9 pg/ml, respectively). Aβ43 and all core biomarkers were significantly altered in patients with AD compared to corresponding controls. NF-L was significantly increased in early-onset AD compared to younger controls, an effect not found between the older groups. Relationships between the Ab peptides and tau proteins, YKL-40, NF-L, GFAP and progranulin were also investigated without finding marked associations. However, age-associated increases in levels of tau proteins, YKL-40, NF-L and GFAP were found with respect to age in healthy controls. Results for these other analytes were similar to previously published data. Aβ43 did not improve diagnostic accuracy in either AD group compared to Aβ42. Discussion: Cerebrospinal fluid Aβ43, but not Aβ42 levels, varied significantly with age in patients with AD. If CSF levels of Aβ peptides reflect amyloid deposition in brain, the possibility arises that there is a difference between Aβ43 and Aβ42 deposition in younger compared to older brain. However, the level of Aβ43 in CSF shows no improvement over Aβ42 regarding diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer's disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer's disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer's disease has never been assessed. Materials and Methods: In this observational study, CSF Aβ43 was measured with ELISA in 89 subjects; 34 with subjective cognitive decline (SCD), 51 with MCI, and four with resolution of previous cognitive complaints. All subjects underwent structural MRI; 40 subjects on a 3T and 50 on a 1.5T scanner. Forty subjects, including 24 with SCD and 12 with MCI, underwent 18F-Flutemetamol PET. Seventy-eight subjects were assessed with 18F-fluorodeoxyglucose PET (21 SCD/7 MCI and 11 SCD/39 MCI on two different scanners). Ten subjects with SCD and 39 with MCI also underwent diffusion tensor imaging. Results: Cerebrospinal fluid Abβ3 was both alone and together with p-tau a significant predictor of the distinction between SCD and MCI. There was a marked difference in CSF Aβ43 between subjects with 18F-Flutemetamol PET scans visually interpreted as negative (37 pg/ml, n = 27) and positive (15 pg/ml, n = 9), p < 0.001. Both CSF Aβ43 and Aβ42 were negatively correlated with standardized uptake value ratios for all analyzed regions; CSF Aβ43 average rho -0.73, Aβ42 -0.74. Both CSF Aβ peptides correlated significantly with hippocampal volume, inferior parietal and frontal cortical thickness and axial diffusivity in the corticospinal tract. There was a trend toward CSF Aβ42 being better correlated with cortical glucose metabolism. None of the studied correlations between CSF Aβ43/42 and imaging biomarkers were significantly different for the two Aβ peptides when controlling for multiple testing. Conclusion: Cerebrospinal fluid Aβ43 appears to be strongly correlated with cerebral amyloid deposits in the same way as Aβ42, even in non-demented patients with only subjective cognitive complaints. Regarding imaging biomarkers, there is no evidence from the present study that CSF Aβ43 performs better than the classical CSF biomarker Aβ42 for distinguishing SCD and MCI. [ABSTRACT FROM AUTHOR]

Background: α-Synuclein has been proposed as a potential biomarker for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, results from α-synuclein measurements in cerebrospinal fluid (CSF) have been inconclusive, and to our knowledge, longitudinal studies of changes prior to the AD diagnosis have not been investigated. Methods: Levels of α-synuclein at baseline and after one and two years were measured in CSF, by enzyme-linked immunosorbent assay. Twenty-six patients with early AD (AD-AD), 48 patients with aMCI, subdivided as 23 that developed AD during follow-up (MCI-AD), and 25 that did not (MCI-MCI), and 25 healthy control individuals, were included. One-way ANOVA was applied to compare mean α-synuclein baseline values between all four study groups, and a linear mixed model was used to compare mean change over time between the three patient groups. Linear associations between α-synuclein and amyloid-β 1-42 (Aβ42), amyloid-β 1-40 (Aβ40), total tau and phosphorylated tau were also examined. Results: A large variation in individual α-synuclein CSF levels was observed, particularly in the MCI-AD group. No significant differences were found in mean α-synuclein levels between all the study groups at baseline. When using a linear mixed model, no significant differences were found at follow-up for estimated mean changes between the patient groups. MCI-AD patients with short duration of symptoms prior to inclusion in the study (=2 years) had considerably higher mean CSF α-synuclein levels compared to patients with a longer symptom duration (802.2 vs. 442.8 pg/mL, p = 0.01). No such difference was seen in the MCI-MCI or AD-AD groups. Significant linear associations (p < 0.0005) between α-synuclein and Aβ40, total tau and phosphorylated tau were found. Conclusion: The observed difference in mean CSF α-synuclein level according to duration of symptoms in the MCI-AD group, may be an indication of changes related to disease progression. However, the lack of significant differences between groups, as well as the large individual variation in CSF levels of α-synuclein in the present study, suggest that α-synuclein is not a useful biomarker for AD. [ABSTRACT FROM AUTHOR]

Background: A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias.Objective: To determine the association of BCHE-K and APOEɛ4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) patients.Methods: Genomic DNA from 368 subjects (108 AD, 174 DLB, and 86 controls) from two routine clinical cohort studies in Norway; DemVest and TrønderBrain, were genotyped for BCHE-K and APOEɛ4. The mild dementia DemVest subjects received annual Mini-Mental State Examination assessments for five years.Results: BCHE-K frequency was lower in DLB (33.9% ; p <  0.01) than in control subjects (51.2%), and was numerically lower in AD as well (38.9% ; p = 0.11). More rapid cognitive decline was associated with the APOEɛ4 genotype, but not with the BCHE-K genotype. In an exploratory analysis of patients who completed all five follow-up visits, there was greater cognitive decline in BCHE-K carriers in the presence of the APOEɛ4 allele than in the absence of these polymorphisms.Conclusion: BCHE-K is associated with a reduced risk for AD and DLB whereas APOEɛ4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOEɛ4 and BCHE-K alleles require prospective confirmation in well-controlled trials. [ABSTRACT FROM AUTHOR]

Introduction: Biomarkers that will reliably predict the onset of Alzheimer's disease (AD) are urgently needed. Although cerebrospinal fluid (CSF) amyloid beta 1-42 (Aß42), total tau, and phosphorylated tau can be used to complement the clinical diagnosis of AD, amnestic mild cognitive impairment (aMCI), the prodromal phase of AD, is heterogeneous. Biomarkers should be able to determine which patients with aMCI are at greatest risk of AD. Histological studies and animal models indicate that amyloid beta 1-43 (Aß43) aggregates early, and may play a role in the pathological process of AD. We have examined levels of CSF Aß43 in a 2-year longitudinal study of aMCI and early AD. Materials and Methods: Cerebrospinal fluid was collected at baseline, and after one and 2 years from patients with AD (n D 19), and patients with aMCI (n D 42). Of these, 21 progressed to AD during the 2 years of study, whereas 21 did not. Controls (n D 32) were lumbar punctured at baseline only. CSF analyses of Aß43, Aß42, and total tau were carried out with ELISA. Results: At baseline, CSF Aß43, CSF Aß42 and ratios with total tau could be used to separate controls from all three patient groups. CSF Aß43, but not Aß42, could separate patients with aMCI who progressed to AD during the 2 years of follow-up, from those that did not. The CSF total tau/Aß43 ratio had a slightly but significantly larger area under the receiver operating characteristic curve when compared to the CSF total tau/Aß42 ratio. CSF Aß43 levels, but not Aß42 levels, decreased from baseline to 2 years in the AD group. Discussion and Conclusion: CSF Aß43 was demonstrated to be significantly reduced in patients already by the time that aMCI or AD was diagnosed, compared to controls, and this change must have occurred during the preclinical period. Since our results suggested that CSF Aß43 distinguishes between subgroups of patients with aMCI better than CSF Aß42, it may prove to be a useful additional biomarker for identifying aMCI patients at greatest risk of AD. [ABSTRACT FROM AUTHOR]