Blood Pressure and T-Tau in Spinal Fluid Are Associated With Delayed Recall in Participants With Memory Complaints and Dementia of the Alzheimer’s Type

Objective: The aim of the study was to determine if systolic blood pressure (SBP), total-tau (t-tau), and beta-amyloid (Aβ) in the cerebral spinal fluid (CSF) were associated with the results on the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) immediate and delayed recall, and the Mini Mental State Examination (MMSE) in “younger” older adults, controlling for age and sex. Method: We included 72 participants, mean age: 62.9 (SD 8.6, range 41–76) from a Norwegian memory clinic; eight were diagnosed with subjective cognitive decline, 32 with mild cognitive impairment (MCI), 30 with dementia of the Alzheimer’s type (DAT), and two with combined DAT and vascular dementia (VaD). Data were examined in three fitted multiple linear regression models using the CERAD-WL immediate and delayed recall, and MMSE as dependent variables; and SBP, t-tau, and Aβ as independent variables, controlling for age and sex. Results: The strongest associations were found in the model using CERAD-WL delayed recall as the dependent variable, where 45% of the variance was explained (standardized Beta = −0.313, p = 0.004 for t-tau and standardized Beta −0.238, p = 0.01 for SBP). The unique contribution of age was close to 8%, t-tau close to 7%, and SBP above 5%. When cardiovascular medication was entered into the analysis, the explained variance increased to 51% and Aβ became significant (standardized Beta = 0.216, p = 0.03). Participants on this medication exhibited worse performance on CERAD-WL delayed recall than those who were not on medication. Age (7%), t-tau (6%), and SBP (5%) showed the same unique contribution, whereas medication contributed 6% and Aβ contributed 4%. CERAD-WL immediate recall, and MMSE yielded similar findings, but explained variance was poorer for these two variables. Conclusions: Both elevated SBP and t-tau were associated with poorer cognitive performance, especially delayed recall. Those on cardiovascular medication were more impaired than were participants who were not on this medication—a finding that probably reflected cerebral incidents in the medicated group.publishedVersio

Blood Pressure in Different Dementia Disorders, Mild Cognitive Impairment, and Subjective Cognitive Decline

The aim of the study was to investigate whether blood pressure (BP) differed among people with different dementia diagnoses, mild cognitive impairment, and subjective cognitive decline and whether BP differences were observed across age and sex. Our study population comprised clinical data from 6,236 patients (53.5% women) aged 45–97 years (Mean = 73.9, SD = 9.6) referred to dementia assessment in 42 outpatient clinics across Norway during 2009–2019. Patients with the following diagnoses were included: Subjective cognitive decline (SCD), Mild cognitive impairment (MCI), dementia due to Alzheimer’s disease (AD), Vascular dementia (VaD), mixed AD and VaD, and dementia in Parkinson’s disease/Lewy body disease (PDD/LBD). For all diagnostic groups, SBP increased with age until about 80 years, after which it trended downward, whereas DBP declined after 60 years of age for all diagnostic groups. Patients aged 65 years and younger with SCD had lower SBP compared to AD patients at the same age, but SBP increased rapidly with increasing age, resulting in a substantially higher SBP at 80 + years compared with all other diagnostic groups. No other differences in SBP or diastolic blood pressure (DBP) were found among patients with the different dementia diagnosis. Neither SBP nor DBP differed between MCI and AD groups. An interaction between age and gender was found for SBP at younger ages, as women started out with a lower pressure than men did but ended up with higher SBP. Conclusion: Among 80+ patients, blood pressure did not differ as a function of the various dementia disorders. The SBP for the SCD patients of various age groups differed from all other diagnostic groups, indicating either that internal regulation of BP in older people is a risk factor for dementia or that brain damage causing dementia or MCI may led to changes in blood pressure. Brain aging seems to influence SBP differently in men and womenpublishedVersio

Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status

The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied.publishedVersio

Prediction of Mild Cognitive Impairment that Evolves into Alzheimer&apos;s Disease Dementia within Two Years using a Gene Expression Signature in Blood: A Pilot Study

Abstract. Background: The focus on Alzheimer&apos;s disease (AD) is shifting from dementia to the prodromal stage of the disorder, to a large extent due to increasing efforts in trying to develop disease modifying treatment for the disorder. For development of diseasemodifying drugs, a reliable and accurate test for identification of mild cognitive impairment (MCI) due to AD is essential. Objective: In the present study, MCI progressing to AD will be predicted using blood-based gene expression. Material and Methods: Gene expression analysis using qPCR was performed on blood RNA from a cohort of patients with amnestic MCI (aMCI; n = 66). Within the aMCI cohort, patients progressing to AD within 1 to 2 years were grouped as MCI converters (n = 34) and the patients remaining at the MCI stage after 2 years were grouped as stable MCI (n = 32). AD and control populations were also included in the study. Results: Multivariate statistical method partial least square regression was used to develop predictive models which later were tested using leave-one-out cross validation. Gene expression signatures that identified aMCI subjects that progressed to AD within 2 years with a prediction accuracy of 74%-77% were identified for the complete dataset and subsets thereof. Conclusion: The present pilot study demonstrates for the first time that MCI that evolves into AD dementia within 2 years may be predicted by analyzing gene expression in blood. Further studies will be needed to validate this gene signature as a potential test for AD in the predementia stage

Cohort profile: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) - a national research and quality registry with a biomaterial collection

Purpose: The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data. Participants: The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009–2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders. Findings to date: All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources. Future plans: The finish date of NorCog was originally in 2029. In 2021, the registry’s legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.publishedVersio

Blood Pressure and T-Tau in Spinal Fluid Are Associated With Delayed Recall in Participants With Memory Complaints and Dementia of the Alzheimer’s Type

Objective: The aim of the study was to determine if systolic blood pressure (SBP), total-tau (t-tau), and beta-amyloid (Aβ) in the cerebral spinal fluid (CSF) were associated with the results on the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) immediate and delayed recall, and the Mini Mental State Examination (MMSE) in “younger” older adults, controlling for age and sex. Method: We included 72 participants, mean age: 62.9 (SD 8.6, range 41–76) from a Norwegian memory clinic; eight were diagnosed with subjective cognitive decline, 32 with mild cognitive impairment (MCI), 30 with dementia of the Alzheimer’s type (DAT), and two with combined DAT and vascular dementia (VaD). Data were examined in three fitted multiple linear regression models using the CERAD-WL immediate and delayed recall, and MMSE as dependent variables; and SBP, t-tau, and Aβ as independent variables, controlling for age and sex. Results: The strongest associations were found in the model using CERAD-WL delayed recall as the dependent variable, where 45% of the variance was explained (standardized Beta = −0.313, p = 0.004 for t-tau and standardized Beta −0.238, p = 0.01 for SBP). The unique contribution of age was close to 8%, t-tau close to 7%, and SBP above 5%. When cardiovascular medication was entered into the analysis, the explained variance increased to 51% and Aβ became significant (standardized Beta = 0.216, p = 0.03). Participants on this medication exhibited worse performance on CERAD-WL delayed recall than those who were not on medication. Age (7%), t-tau (6%), and SBP (5%) showed the same unique contribution, whereas medication contributed 6% and Aβ contributed 4%. CERAD-WL immediate recall, and MMSE yielded similar findings, but explained variance was poorer for these two variables. Conclusions: Both elevated SBP and t-tau were associated with poorer cognitive performance, especially delayed recall. Those on cardiovascular medication were more impaired than were participants who were not on this medication—a finding that probably reflected cerebral incidents in the medicated group

Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status

The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied

Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status

The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied

Blood Pressure in Different Dementia Disorders, Mild Cognitive Impairment, and Subjective Cognitive Decline

The aim of the study was to investigate whether blood pressure (BP) differed among people with different dementia diagnoses, mild cognitive impairment, and subjective cognitive decline and whether BP differences were observed across age and sex. Our study population comprised clinical data from 6,236 patients (53.5% women) aged 45–97 years (Mean = 73.9, SD = 9.6) referred to dementia assessment in 42 outpatient clinics across Norway during 2009–2019. Patients with the following diagnoses were included: Subjective cognitive decline (SCD), Mild cognitive impairment (MCI), dementia due to Alzheimer’s disease (AD), Vascular dementia (VaD), mixed AD and VaD, and dementia in Parkinson’s disease/Lewy body disease (PDD/LBD). For all diagnostic groups, SBP increased with age until about 80 years, after which it trended downward, whereas DBP declined after 60 years of age for all diagnostic groups. Patients aged 65 years and younger with SCD had lower SBP compared to AD patients at the same age, but SBP increased rapidly with increasing age, resulting in a substantially higher SBP at 80 + years compared with all other diagnostic groups. No other differences in SBP or diastolic blood pressure (DBP) were found among patients with the different dementia diagnosis. Neither SBP nor DBP differed between MCI and AD groups. An interaction between age and gender was found for SBP at younger ages, as women started out with a lower pressure than men did but ended up with higher SBP. Conclusion: Among 80+ patients, blood pressure did not differ as a function of the various dementia disorders. The SBP for the SCD patients of various age groups differed from all other diagnostic groups, indicating either that internal regulation of BP in older people is a risk factor for dementia or that brain damage causing dementia or MCI may led to changes in blood pressure. Brain aging seems to influence SBP differently in men and wome

Cognition in Patients With Memory Difficulties and Dementia Relative to APOE e4 Status

The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied