84 research outputs found
Young Onset Dementia in Central Norway
No full textBackground and objective
Dementia is one of the most frequent causes of illness and death in the world, and has social and economic impact on people and communities worldwide. Alzheimer’s disease is the leading cause of all dementia, a syndrome caused by cognitive impairment interfering with the performance of everyday activities. It is characterized by a slowly progressive deterioration of cognitive functions such as memory, orientation and speech. As is the case for all neurodegenerative dementia disorders, Alzheimer’s disease develops over decades before eventually disrupting a person’s independency. Alzheimer pathology progresses in the brain at least a decade before signs of cognitive impairment appear. Often, several years pass before symptoms are recognized as such. For many years, the presence of dementia was obligatory for the diagnosis of Alzheimer’s disease. More recent diagnostic criteria have made it possible to diagnose the disease in the stage of mild cognitive impairment, a predementia phase characterized by cognitive impairment with preserved independency. In this stage, application of biomarkers was of particular importance. Diagnostic criteria for other neurodegenerative cognitive disorders have since developed in a similar way, with the positive effects of patients being recognized in an earlier phase, and researchers being able to identify dementing pathology at less advanced stages. Identification of disease as early as possible will be crucial in the event of medical treatment emerging in the future. Research on the epidemiological aspects of cognitive disorders can be challenging. As age is the major risk factor for dementia, the majority of research on cognitive disorders has focused on late onset dementia, characterized by symptoms appearing after the age of 65. However, dementia is not limited to older populations. Although research is scarce, younger persons can also be affected. Young onset dementia is defined as dementia occurring before the age of 65. As young onset dementia is a low frequency condition, research on epidemiological aspects is especially laborious, and requires a larger catchment area compared to studies on older populations. A majority of studies presenting epidemiological estimates of dementia have typically been designed to target disabilities among persons above the age of 60 to 70 years, leading to the specific bias of low numbers in younger subgroups. The estimates of young onset dementia provided in these studies are therefore of lower precision, though frequently cited in research, and by governments budgeting the costs of healthcare. There have only been a few publications focusing on the prevalence and incidence of dementia in younger persons. In these studies, estimates vary substantially. Differences in study design, cultural attitudes, as well as disparities within the healthcare systems, account for most of the discrepancies. Importantly, some studies are based on high quality dementia registries or tertiary clinics, others are community based; the former providing better diagnostics and higher specificity, the latter a lower level of diagnostic verification but higher sensitivity. Though young patients are likely to be assessed in hospitals, consensus exists that a population-based approach is preferred. The main object of “UngDemens I Trøndelag” was to explore epidemiological aspects of young onset dementia in a defined catchment area in central Norway (Trøndelag). A large population, in combination with a multiple sourced case ascertainment process, the routine employment of biomarkers such as magnetic resonance imaging and cerebrospinal fluid analysis in hospitals, and a meticulous review of every participant included, provided us with a relatively large dataset of high clinical accuracy. The first and second publication provided estimates on the prevalence, incidence and subtypes of dementia, while the third article focused on the diagnostic delays and the pathway to diagnosis for young onset Alzheimer’s disease, a frequent cause of dementia among people under the age of 65. Material and methods.
Materials and methods
The project was performed in Trøndelag, a geographically and administratively defined area with a population of almost 450 000. Trøndelag is heterogeneous in the distribution of urban and rural areas, hospital sizes, and the population is representative of that of the rest of the country. Healthcare in Norway is largely publicly organized, and readily accessible. All patients are assigned to a general practitioner, usually responsible for all referrals to hospitals. Though a diagnosis of dementia in the elderly is frequently made by community healthcare services, patients with suspected cognitive impairment under the age of 65 are evaluated by a qualified hospital physician. The primary source of patient identification was the Department of Neurology, University Hospital of Trondheim, and the memory clinic of the Department of Psychiatry, Levanger Hospital. Both departments are main referral sites of YOD in their catchment area, covering over 90 % of the target area. Secondary sources were hospital records from all three hospitals in the target area, specialized outpatient services for individuals with intellectual disabilities in both Trondheim and Levanger, and collaborating physicians in relevant hospital departments in Trøndelag. At a community level we worked closely with dementia coordinators and other relevant healthcare workers in frequent contact with young patients with cognitive disorders. Healthcare workers at every nursing home were individually contacted by telephone to ensure patients at all stages of the disease were identified. A regional centre for Huntington’s disease provided information on patients with dementia. The inclusion period was between July 2014 and July 2018.
The project accepted all patients diagnosed with young onset dementia or mild cognitive impairment due to Alzheimer’s disease. Patients were individually verified by researchers either by personal assessment, or by reviewing referrals from the general practitioner and relevant hospital notes. A telephone interview with a close family member was conducted. The project collected various data on demographics, time lags, initial symptoms, and results of hospital investigations. Included patients were either consenting or non-consenting. In cases where patients did not consent, the Regional Committee for Medical and Health Research Ethics allowed the project to include participants to the extent that we only collected data on age, sex and diagnosis. Validated diagnostic criteria were applied for all diagnoses.
Results
The project identified a total of 410 patients who met the inclusion criteria. Of these, 390 patients had a diagnosis of dementia on census day. Close to 80 % of dementias were caused by a neurodegenerative disease in an otherwise heterogeneous group of dementia subtypes, identifying 17 different causes in total. Alzheimer’s disease was the most frequent cause of dementia, accounting for approximately 55 % of all dementias. There were no significant differences in sex. A total of 171 of the prevalent cases were between the age of 30 and 64 on census date, yielding a prevalence of 85.5 per 100 000 persons at risk in the age category of 30-64 years, and 143.1 per 100 000 in the age category of 45-64 years. The prevalence of the most common subtypes of dementia were calculated, Alzheimer’s disease being the largest displaying a prevalence of 37.0 and 65.4 per 100 000 persons at risk in the respective age categories. The project also produced prevalence rates for both dementia and most prevalent subtypes according to age (in five-year bands) and sex. To provide incidence rates for the same age groups, we identified patients diagnosed with dementia in the years 2015, 2016 and 2017. A total of 89 incident cases of dementia were identified, resulting in an incidence of 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 per 100 000 person-years. The distribution of subtypes was similar to the prevalent cases; diverse, dominated by neurodegenerative disease, and AD causing almost half of all dementias. A total of 41 males and 48 females were identified, resembling the sex distribution in the prevalence study. A total of 223 patients diagnosed with typical young onset Alzheimer’s disease were included in a study of the diagnostic delays among these patients. Patients with mild cognitive impairment were included if biomarkers displayed signs of Alzheimer’s pathology, fulfilling 2007 International Work Group criteria for Alzheimer’s disease. The diagnosis of mild cognitive impairment due to Alzheimer’s disease was more frequent after 2012, accounting for 43 of the total 45 patients who received a diagnosis in the pre-dementia phase. Time from onset of symptoms to diagnosis was 5.5 years. The time from onset to initial contact with the healthcare system, mainly through the general practitioner, was almost three and a half years. Time from contact to first visit at the hospital exceeded ten months, resulting in a period of almost 15 months of clinical investigations, and over five visits, before AD was diagnosed. Mini Mental Status Evaluation was normal in most patients, or only marginally pathological when performed for the first time. The analysis of cerebrospinal fluid core biomarkers was performed eight months after the patient’s first visit to the hospital
Mapping of cognitive function in patients who has undergone bariatric surgery
No full textBakgrunn: Studier viser både at fedme kan påvirke kognitiv funksjon negativt og at kognitiv funksjon bedres etter bariatrisk kirurgi. Imidlertid rapporterer fedmeopererte pasienter ved St. Olavs Hospital ikke sjelden redusert hukommelse postoperativt. Flere studier har kartlagt kognitiv funksjon hos pasienter med fedme, før og etter kirurgi, ved bruk av objektive kognitive tester. Selvopplevd hukommelse hos fedmeopererte pasienter er i liten utstrekning studert. Hensikt: Hensikten med studien var å registrere subjektiv opplevelse av hukommelse hos en stor gruppe fedmeopererte pasienter og hos ikke-opererte pasienter med fedme. Dette ble gjort for å kartlegge utbredelse av selvopplevd nedsatt hukommelse hos pasienter etter bariatrisk kirurgi. Videre ønsket vi å undersøke om objektive tester kunne bekrefte funn fra den subjektive kartleggingen, samt vurdere eventuell assosiasjon mellom den subjektive kartleggingen og de objektive testene. Metode: Studien ble designet som en komparativ tverrsnittsstudie. Utvalget bestod av fedmeopererte (n=292) og en kontrollgruppe bestående av ikke-opererte pasienter med fedme (n=91). Den subjektive kartleggingen av hukommelse ble gjort ved bruk av «The Everyday Memory Questionnaire» (EMQ). I tillegg ble et underutvalg fra begge grupper (n=77) testet med objektive kognitive tester ved St. Olavs Hospital. Assosiasjon mellom totalskår i EMQ og resultater fra de objektive kognitive testene ble vurdert. Resultater: Fedmeopererte pasienter rapporterte statistisk signifikant dårligere hukommelse, målt med EMQ (p=0,001), enn pasientene i kontrollgruppen. De objektive kognitive testene viste ingen statistisk signifikant forskjell mellom gruppene. Det var statistisk signifikant negativ assosiasjon mellom EMQ-skår og utsatt gjenkalling ved tiordstest (p=0,02), men det ble ikke funnet signifikante assosiasjoner mellom EMQ-skår og de øvrige objektive kognitive tester. Konklusjon: Fedmeopererte pasienter anga signifikant dårligere selvopplevd hukommelse enn kontrollgruppen. Forskjellen kunne ikke gjenfinnes ved objektiv kognitiv testing. Selvopplevd nedsatt hukommelse var assosiert med testresultatet for utsatt gjenkalling ved tiordstest, men ikke med de øvrige testresultatene. Vi kan ikke konkludere med at kognitiv funksjon påvirkes negativt av bariatrisk kirurgi. For å forstå sammenhengen mellom opplevelsen av nedsatt hukommelse og bariatrisk kirurgi bør både longitudinelle studier og kvalitative studier gjennomføres. Relevans: Stadig flere pasienter gjennomgår bariatrisk kirurgi. Det økende volumet av inngrep samt utviklingen av nye bariatriske prosedyrer gjør at helsepersonell må være oppmerksomme på mulige langtidskomplikasjoner etter kirurgi.Masteroppgaven tilgjengelig fra 2020-06-01
Kartlegging av kognitiv funksjon hos pasienter som har gjennomgått bariatrisk kirurgi
No full textBakgrunn: Studier viser både at fedme kan påvirke kognitiv funksjon negativt og at kognitiv funksjon bedres etter bariatrisk kirurgi. Imidlertid rapporterer fedmeopererte pasienter ved St. Olavs Hospital ikke sjelden redusert hukommelse postoperativt. Flere studier har kartlagt kognitiv funksjon hos pasienter med fedme, før og etter kirurgi, ved bruk av objektive kognitive tester. Selvopplevd hukommelse hos fedmeopererte pasienter er i liten utstrekning studert. Hensikt: Hensikten med studien var å registrere subjektiv opplevelse av hukommelse hos en stor gruppe fedmeopererte pasienter og hos ikke-opererte pasienter med fedme. Dette ble gjort for å kartlegge utbredelse av selvopplevd nedsatt hukommelse hos pasienter etter bariatrisk kirurgi. Videre ønsket vi å undersøke om objektive tester kunne bekrefte funn fra den subjektive kartleggingen, samt vurdere eventuell assosiasjon mellom den subjektive kartleggingen og de objektive testene. Metode: Studien ble designet som en komparativ tverrsnittsstudie. Utvalget bestod av fedmeopererte (n=292) og en kontrollgruppe bestående av ikke-opererte pasienter med fedme (n=91). Den subjektive kartleggingen av hukommelse ble gjort ved bruk av «The Everyday Memory Questionnaire» (EMQ). I tillegg ble et underutvalg fra begge grupper (n=77) testet med objektive kognitive tester ved St. Olavs Hospital. Assosiasjon mellom totalskår i EMQ og resultater fra de objektive kognitive testene ble vurdert. Resultater: Fedmeopererte pasienter rapporterte statistisk signifikant dårligere hukommelse, målt med EMQ (p=0,001), enn pasientene i kontrollgruppen. De objektive kognitive testene viste ingen statistisk signifikant forskjell mellom gruppene. Det var statistisk signifikant negativ assosiasjon mellom EMQ-skår og utsatt gjenkalling ved tiordstest (p=0,02), men det ble ikke funnet signifikante assosiasjoner mellom EMQ-skår og de øvrige objektive kognitive tester. Konklusjon: Fedmeopererte pasienter anga signifikant dårligere selvopplevd hukommelse enn kontrollgruppen. Forskjellen kunne ikke gjenfinnes ved objektiv kognitiv testing. Selvopplevd nedsatt hukommelse var assosiert med testresultatet for utsatt gjenkalling ved tiordstest, men ikke med de øvrige testresultatene. Vi kan ikke konkludere med at kognitiv funksjon påvirkes negativt av bariatrisk kirurgi. For å forstå sammenhengen mellom opplevelsen av nedsatt hukommelse og bariatrisk kirurgi bør både longitudinelle studier og kvalitative studier gjennomføres. Relevans: Stadig flere pasienter gjennomgår bariatrisk kirurgi. Det økende volumet av inngrep samt utviklingen av nye bariatriske prosedyrer gjør at helsepersonell må være oppmerksomme på mulige langtidskomplikasjoner etter kirurgi
Young Onset Dementia in Central Norway
No full textBackground and objective
Dementia is one of the most frequent causes of illness and death in the world, and has social and economic impact on people and communities worldwide. Alzheimer’s disease is the leading cause of all dementia, a syndrome caused by cognitive impairment interfering with the performance of everyday activities. It is characterized by a slowly progressive deterioration of cognitive functions such as memory, orientation and speech. As is the case for all neurodegenerative dementia disorders, Alzheimer’s disease develops over decades before eventually disrupting a person’s independency. Alzheimer pathology progresses in the brain at least a decade before signs of cognitive impairment appear. Often, several years pass before symptoms are recognized as such. For many years, the presence of dementia was obligatory for the diagnosis of Alzheimer’s disease. More recent diagnostic criteria have made it possible to diagnose the disease in the stage of mild cognitive impairment, a predementia phase characterized by cognitive impairment with preserved independency. In this stage, application of biomarkers was of particular importance. Diagnostic criteria for other neurodegenerative cognitive disorders have since developed in a similar way, with the positive effects of patients being recognized in an earlier phase, and researchers being able to identify dementing pathology at less advanced stages. Identification of disease as early as possible will be crucial in the event of medical treatment emerging in the future. Research on the epidemiological aspects of cognitive disorders can be challenging. As age is the major risk factor for dementia, the majority of research on cognitive disorders has focused on late onset dementia, characterized by symptoms appearing after the age of 65. However, dementia is not limited to older populations. Although research is scarce, younger persons can also be affected. Young onset dementia is defined as dementia occurring before the age of 65. As young onset dementia is a low frequency condition, research on epidemiological aspects is especially laborious, and requires a larger catchment area compared to studies on older populations. A majority of studies presenting epidemiological estimates of dementia have typically been designed to target disabilities among persons above the age of 60 to 70 years, leading to the specific bias of low numbers in younger subgroups. The estimates of young onset dementia provided in these studies are therefore of lower precision, though frequently cited in research, and by governments budgeting the costs of healthcare. There have only been a few publications focusing on the prevalence and incidence of dementia in younger persons. In these studies, estimates vary substantially. Differences in study design, cultural attitudes, as well as disparities within the healthcare systems, account for most of the discrepancies. Importantly, some studies are based on high quality dementia registries or tertiary clinics, others are community based; the former providing better diagnostics and higher specificity, the latter a lower level of diagnostic verification but higher sensitivity. Though young patients are likely to be assessed in hospitals, consensus exists that a population-based approach is preferred. The main object of “UngDemens I Trøndelag” was to explore epidemiological aspects of young onset dementia in a defined catchment area in central Norway (Trøndelag). A large population, in combination with a multiple sourced case ascertainment process, the routine employment of biomarkers such as magnetic resonance imaging and cerebrospinal fluid analysis in hospitals, and a meticulous review of every participant included, provided us with a relatively large dataset of high clinical accuracy. The first and second publication provided estimates on the prevalence, incidence and subtypes of dementia, while the third article focused on the diagnostic delays and the pathway to diagnosis for young onset Alzheimer’s disease, a frequent cause of dementia among people under the age of 65. Material and methods.
Materials and methods
The project was performed in Trøndelag, a geographically and administratively defined area with a population of almost 450 000. Trøndelag is heterogeneous in the distribution of urban and rural areas, hospital sizes, and the population is representative of that of the rest of the country. Healthcare in Norway is largely publicly organized, and readily accessible. All patients are assigned to a general practitioner, usually responsible for all referrals to hospitals. Though a diagnosis of dementia in the elderly is frequently made by community healthcare services, patients with suspected cognitive impairment under the age of 65 are evaluated by a qualified hospital physician. The primary source of patient identification was the Department of Neurology, University Hospital of Trondheim, and the memory clinic of the Department of Psychiatry, Levanger Hospital. Both departments are main referral sites of YOD in their catchment area, covering over 90 % of the target area. Secondary sources were hospital records from all three hospitals in the target area, specialized outpatient services for individuals with intellectual disabilities in both Trondheim and Levanger, and collaborating physicians in relevant hospital departments in Trøndelag. At a community level we worked closely with dementia coordinators and other relevant healthcare workers in frequent contact with young patients with cognitive disorders. Healthcare workers at every nursing home were individually contacted by telephone to ensure patients at all stages of the disease were identified. A regional centre for Huntington’s disease provided information on patients with dementia. The inclusion period was between July 2014 and July 2018.
The project accepted all patients diagnosed with young onset dementia or mild cognitive impairment due to Alzheimer’s disease. Patients were individually verified by researchers either by personal assessment, or by reviewing referrals from the general practitioner and relevant hospital notes. A telephone interview with a close family member was conducted. The project collected various data on demographics, time lags, initial symptoms, and results of hospital investigations. Included patients were either consenting or non-consenting. In cases where patients did not consent, the Regional Committee for Medical and Health Research Ethics allowed the project to include participants to the extent that we only collected data on age, sex and diagnosis. Validated diagnostic criteria were applied for all diagnoses.
Results
The project identified a total of 410 patients who met the inclusion criteria. Of these, 390 patients had a diagnosis of dementia on census day. Close to 80 % of dementias were caused by a neurodegenerative disease in an otherwise heterogeneous group of dementia subtypes, identifying 17 different causes in total. Alzheimer’s disease was the most frequent cause of dementia, accounting for approximately 55 % of all dementias. There were no significant differences in sex. A total of 171 of the prevalent cases were between the age of 30 and 64 on census date, yielding a prevalence of 85.5 per 100 000 persons at risk in the age category of 30-64 years, and 143.1 per 100 000 in the age category of 45-64 years. The prevalence of the most common subtypes of dementia were calculated, Alzheimer’s disease being the largest displaying a prevalence of 37.0 and 65.4 per 100 000 persons at risk in the respective age categories. The project also produced prevalence rates for both dementia and most prevalent subtypes according to age (in five-year bands) and sex. To provide incidence rates for the same age groups, we identified patients diagnosed with dementia in the years 2015, 2016 and 2017. A total of 89 incident cases of dementia were identified, resulting in an incidence of 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 per 100 000 person-years. The distribution of subtypes was similar to the prevalent cases; diverse, dominated by neurodegenerative disease, and AD causing almost half of all dementias. A total of 41 males and 48 females were identified, resembling the sex distribution in the prevalence study. A total of 223 patients diagnosed with typical young onset Alzheimer’s disease were included in a study of the diagnostic delays among these patients. Patients with mild cognitive impairment were included if biomarkers displayed signs of Alzheimer’s pathology, fulfilling 2007 International Work Group criteria for Alzheimer’s disease. The diagnosis of mild cognitive impairment due to Alzheimer’s disease was more frequent after 2012, accounting for 43 of the total 45 patients who received a diagnosis in the pre-dementia phase. Time from onset of symptoms to diagnosis was 5.5 years. The time from onset to initial contact with the healthcare system, mainly through the general practitioner, was almost three and a half years. Time from contact to first visit at the hospital exceeded ten months, resulting in a period of almost 15 months of clinical investigations, and over five visits, before AD was diagnosed. Mini Mental Status Evaluation was normal in most patients, or only marginally pathological when performed for the first time. The analysis of cerebrospinal fluid core biomarkers was performed eight months after the patient’s first visit to the hospital
Amyloid beta 1-43 as a potential biomarker for the detection of early Alzheimer’s disease
No full textProteins associated with core biomarkers in early Alzheimer`s disease: A pilot study of levels in cerebrospinal fluid, serum or plasma
No full textBackground:The cerebrospinal fluid (CSF) biomarkers amyloid-beta 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) are considered to reflect core pathological features of Alzheimer’s disease (AD), and have consistently been reported to have high diagnostic accuracy for discriminating patients with AD from healthy elderly controls. Yet there are limitations to their use, and little is known about alternative proteins in CSF, as well as in blood. The failure of Aβ immunotherapy has forced AD research to examine additional factors, particularly in the early stages of disease. The APOE ε4 allele is the major genetic risk factor for sporadic AD, and data suggest that ApoE may alter Aβ clearance and/or metabolism during the disease process. Another apolipoprotein associated with Aβ metabolism is clusterin (ApoJ), suggested to prevent aggregation and also be involved in clearance of Aβ. Moreover, angiotensin-converting enzyme (ACE) is a protease known to mediate cleavage of Aβ in vitro, and there is some indication that the ACE gene may be a risk factor for AD, depending on the insertion/deletion (I/D) genotype. Neurofilament-light (NF-L), like tau, is a neuronal cytoskeletal protein. In this pilot study, levels of ApoE, clusterin, ACE and NF-L in CSF and/or blood have been investigated in patients with early AD and healthy elderly individuals, and comparisons made with ACE and APOE ε4-allele genotype.
Aims: To assess whether levels of these proteins altered significantly in early AD compared to levels in elderly control individuals healthy for their age, whether additional information could be obtained from comparisons with ACE and APOE polymorphisms, and to assess their potential diagnostic value as early-stage biomarkers for AD compared to Aβ and tau protein.
Methods: Commercial ELISA kits were used to analyze and compare the levels of Aβ42, Aβ40, T-tau, P-tau, ApoE, clusterin, ACE and NF-L in CSF and/or plasma or serum samples from 20 patients with early AD and 20 age-matched individuals healthy for their age. Real-time polymerase chain reaction was performed on genomic DNA purified from samples of whole-blood from all participants to determine the ACE I/D polymorphism. Comparison was also made regarding APOE ε4-allele status.
Results: Despite the low number of samples, a high diagnostic accuracy in the discrimination between patients with early AD and elderly control individuals was obtained with concentrations of Aβ42 and tau in CSF. No significant differences were found between patients with early AD and controls regarding levels of ApoE in serum, clusterin in CSF or plasma, or ACE in CSF or serum. There was no pathological relationship regarding ACE genotype and allele distribution. The APOE ε4-allele was associated with lower levels of serum ApoE, irrespective of diagnosis. CSF NF-L levels were significantly higher in patients compared to controls.
Conclusion: No disease-specific alterations were found in relation to ApoE, clusterin or ACE. Although NF-L in CSF showed a fairly good potential to distinguish the patients with early AD from elderly individuals healthy for their age, the diagnostic accuracy was below that of Aβ and tau protein, and it did not seem to provide improved discrimination as a biomarker. Thus, none of these proteins are likely candidates as biomarkers for early AD
Proteins associated with core biomarkers in early Alzheimer`s disease : A pilot study of levels in cerebrospinal fluid, serum or plasma
No full textBackground:The cerebrospinal fluid (CSF) biomarkers amyloid-beta 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) are considered to reflect core pathological features of Alzheimer’s disease (AD), and have consistently been reported to have high diagnostic accuracy for discriminating patients with AD from healthy elderly controls. Yet there are limitations to their use, and little is known about alternative proteins in CSF, as well as in blood. The failure of Aβ immunotherapy has forced AD research to examine additional factors, particularly in the early stages of disease. The APOE ε4 allele is the major genetic risk factor for sporadic AD, and data suggest that ApoE may alter Aβ clearance and/or metabolism during the disease process. Another apolipoprotein associated with Aβ metabolism is clusterin (ApoJ), suggested to prevent aggregation and also be involved in clearance of Aβ. Moreover, angiotensin-converting enzyme (ACE) is a protease known to mediate cleavage of Aβ in vitro, and there is some indication that the ACE gene may be a risk factor for AD, depending on the insertion/deletion (I/D) genotype. Neurofilament-light (NF-L), like tau, is a neuronal cytoskeletal protein. In this pilot study, levels of ApoE, clusterin, ACE and NF-L in CSF and/or blood have been investigated in patients with early AD and healthy elderly individuals, and comparisons made with ACE and APOE ε4-allele genotype. Aims: To assess whether levels of these proteins altered significantly in early AD compared to levels in elderly control individuals healthy for their age, whether additional information could be obtained from comparisons with ACE and APOE polymorphisms, and to assess their potential diagnostic value as early-stage biomarkers for AD compared to Aβ and tau protein. Methods: Commercial ELISA kits were used to analyze and compare the levels of Aβ42, Aβ40, T-tau, P-tau, ApoE, clusterin, ACE and NF-L in CSF and/or plasma or serum samples from 20 patients with early AD and 20 age-matched individuals healthy for their age. Real-time polymerase chain reaction was performed on genomic DNA purified from samples of whole-blood from all participants to determine the ACE I/D polymorphism. Comparison was also made regarding APOE ε4-allele status. Results: Despite the low number of samples, a high diagnostic accuracy in the discrimination between patients with early AD and elderly control individuals was obtained with concentrations of Aβ42 and tau in CSF. No significant differences were found between patients with early AD and controls regarding levels of ApoE in serum, clusterin in CSF or plasma, or ACE in CSF or serum. There was no pathological relationship regarding ACE genotype and allele distribution. The APOE ε4-allele was associated with lower levels of serum ApoE, irrespective of diagnosis. CSF NF-L levels were significantly higher in patients compared to controls. Conclusion: No disease-specific alterations were found in relation to ApoE, clusterin or ACE. Although NF-L in CSF showed a fairly good potential to distinguish the patients with early AD from elderly individuals healthy for their age, the diagnostic accuracy was below that of Aβ and tau protein, and it did not seem to provide improved discrimination as a biomarker. Thus, none of these proteins are likely candidates as biomarkers for early AD
APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; a case control study from central Norway
No full textBackground: 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.© 2008 Sando et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Incidence of Young Onset Dementia in Central Norway: A Population-Based Study
No full textBackground: 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.publishedVersio
Time to diagnosis in young onset alzheimer's disease: A population-based study from central Norway
No full textBackground: 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
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