Background The introduction of anti-amyloid treatments (AAT) for Alzheimer's disease (AD) has put the cost-effectiveness into focus. Objective Estimate the potential cost-effectiveness of diagnostic pathways combined with AAT for early AD. Methods Diagnostic accuracy of blood-based (BBM) and cerebrospinal fluid (CSF) biomarkers was obtained from Norwegian memory clinics using positron emission tomography (PET) as reference standard. In a health-economic model, the cost-effectiveness of three diagnostic strategies was estimated relying either on BBM (p-tau 217), CSF (Aβ 42/40 ratio), and BBM with CSF confirmatory testing and compared with standard of care (SoC) and compared with CSF-AAT. The model consisted of a decision tree reflecting the diagnostic process and a subsequent Markov cohort model starting at mild cognitive impairment due to AD. All strategies except SoC were combined with AAT including costs of treatment (assumed €5000/year), infusions and monitoring. Results Compared with SoC all three strategies (CSF-AAT, BBM-AAT, and BBM-CSF-AAT) resulted in QALY gains at higher costs, with an incremental cost-effectiveness ratio (ICER) of 110k€, 141k€ and 110k€ respectively. Compared with CSF-AAT both BBM-AAT and BBM-CSF-AAT strategies resulted in QALYs lost at lower costs, with an ICER of 27k€ and 109k€ respectively. Results were particularly sensitive to the price of AAT and possible subcutaneous administration. Conclusions Compared with SoC all three strategies are potentially not cost-effective as they exceeded the Swedish maximum willingness to pay threshold of €94,800 per QALY gained. BBM-CSF-AAT versus CSF-AAT is potentially cost-effective if willing to accept its QALY loss. Discussions on budget impact on different payers are needed after introducing AAT.

Introduction: Vascular risk factors in midlife have been associated with accelerated age-related cognitive decline. However, associations with old-age cardiovascular health are less clear cut and sometimes opposite associations have been observed. The objective of this study was to examine whether change in cardiovascular health, measured using the Life's Simple 7 (LS7) score, is associated with rate of cognitive change in older adults. Methods: We included 1133 participants aged ≥60 years from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, and perceptual speed) across up to 15 years. LS7, assessed at baseline and at the 6-year follow-up, was composed of seven cardiovascular health metrics (smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure). Change in LS7 was calculated as the difference between baseline and 6 years (range -5 to +8 points). Individuals were categorized into “worse” (-5 to 2 points), “same” (-1 to 1 point), or “improve” (2 to 8 points). Linear mixed-effect models were used to examine change in cognitive performance as a function of LS7 change categories. Results: On average, participants slightly improved (M = 0.3, SD = 1.6) their cardiovascular health from baseline to the 6-year follow-up. Participants were classified as “same” (67.1 %), “improve” (21.0 %), and “worse” (11.8 %). The proportion of those who improved their LS7 individual items was higher for total cholesterol and diet, while the largest deterioration was observed in glucose and physical activity. Both the worse and improve categories were associated with faster cognitive decline. Age-stratified analyses revealed that worsening of LS7 was clearly associated with faster cognitive decline in the old-old (≥ 78 years), whereas improvement tended to be associated with faster cognitive decline in the young-old (< 78 years) group. Discussion: Change in cardiovascular health in old age may lead to faster cognitive decline. The results stress the importance of monitoring and maintaining good cardiovascular health also in very old adults and to, above all, avoid worsening of vascular risk factors.

Background Previous research on associations between cardiovascular health, measured at a single timepoint, and rate of age-related cognitive decline shows divergent findings dependent on the participants’ age and the health metric studied. The aim of this study was to add to the knowledge in this field by investigating whether change in cardiovascular health, assessed with Life’s Simple 7 (LS7) score, is associated with rate of cognitive change in young-old and old-old adults. Methods The study included 1022 participants aged ≥ 60 years from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, and perceptual speed) across up to 15 years. LS7, composed of seven cardiovascular health metrics (smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure), was assessed at baseline and at the 6-year follow-up. Change in LS7 was calculated as the difference between baseline and 6 years (range − 5 to 8 points) and categorised into worse (−5 to −2 points), stable (−1 to 1 points), and improved (2 to 8 points). Change in cognitive performance as a function of LS7 change categories was estimated using linear mixed-effects models. Results Participants were classified as stable (67.1%), improved (21.0%), or worse (11.8%) according to changes in LS7 score. Both the worse and improved categories were associated with faster cognitive decline. Age-stratified analyses revealed that worsening of LS7 was clearly associated with faster cognitive decline in the old-old (≥ 78 years), whereas improvement tended be associated with faster cognitive decline in the young-old (< 78 years) group. Conclusions Change in cardiovascular health in old age may lead to accelerated cognitive decline, particularly in late senescence. These results suggest that it is important to monitor and maintain cardiovascular health status in very old adults.

OBJECTIVES:The implementation of disease-modifying treatments for Alzheimer's Disease (AD) will require cost-effective diagnostic processes. As part of The Precision Medicine In AD consortium (PMI-AD) project, the aim is to analyze the baseline costs of diagnosing early AD at memory clinics in Norway, Slovenia, and the Netherlands. METHODS:The costs of cognitive testing and a clinical examination, apolipoprotein E, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), positron emission tomography and blood-based biomarkers (BBM), which are used in different combinations in the three countries, were analyzed. Standardized unit costs, adjusted for GDP per capita and based on Swedish conditions were applied. The costs were expressed in euros (€) as of 2019. A diagnostic set comprising clinical examination, cognitive testing, MRI and CSF was defined as the gold standard, with MRI mainly used as an exclusion filter. RESULTS:Cost data were available for 994 persons in Norway, 169 in Slovenia and 1015 in the Netherlands. The mean diagnostic costs were 1478 (95% confidence interval 1433-1523) € in Norway, 851 (731-970) € in Slovenia and 1184 (1135-1232) € in the Netherlands. Norway had the highest unit costs but also the greatest use of tests. With a uniform diagnostic test set applied, the diagnostic costs were 1264 (1238-1291) €, in Norway, 843 (771-914) € in Slovenia and 1184 (1156-1213) € in the Netherlands. There were no major cost differences between the final set of diagnoses. CONCLUSIONS:The total costs for setting a diagnosis of AD varied somewhat in the three countries, depending on unit costs and use of tests. These costs are relatively low in comparison to the societal costs of AD.

Slovenia, situated in Central Europe with a population of 2.1 million, has an estimated 44,278 individuals with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s dementia, rendering them potential candidates for disease-modifying treatment (DMT), such as lecanemab. We identified 114 potential candidates whose real-life expenses for diagnostic process surmount to more than €80,000. Treating all potential candidates nationwide would amount to €1.06 billion, surpassing Slovenia’s entire annual medication expenditure for 2022 (€743 million). The introduction of DMTs and the associated logistics, along with potential complications, will significantly change societal, professional, and patient approach to treatment of Alzheimer’s disease.

Objective The Montreal cognitive assessment scale (MoCA) is commonly used for detecting individuals with mild cognitive impairment (MCI). The aim of the present study was to evaluate the validity of the Slovenian MoCA as a screening tool for MCI and to determine the optimal cut-off point to detect MCI in the elderly population . Methods Mini-Mental State Examination (MMSE), MoCA, and neuropsychological testing assessment were conducted on 93 individuals aged ≥ 60 years. MCI was found in 35 individuals with 58 cognitively asymptomatic controls. Cut-off values, sensitivity, and specificity of MoCA were calculated with the receiver operating characteristic curve. Results MCI and healthy individuals did not differ with respect to age and education. Healthy individuals ( M = 24.5, SD = 1.7) performed significantly better on MoCA compared to MCI individuals ( M = 21.4, SD = 3.2) ( p < 0.001). The Cronbach’s α of MoCA as an index of internal consistency was 0.64. MoCA distinguished between healthy controls and MCI individuals with a sensitivity of 77% and specificity of 74%, using a cut-off of 23/24 points. Conclusion The Slovenian version of MoCA demonstrates an optimal cut-off value of 23/24 points for detecting older individuals with MCI. As a screening tool for MCI, its better diagnostic accuracy makes it preferable to using MMSE.

Objective: We investigated whether vascular risk factors (VRFs), assessed with Life's Simple 7 (LS7), are associated with the rate of cognitive decline in the years preceding a dementia diagnosis. Method: This study included 1,449 stroke-free participants aged >= 60 years from the Swedish National Study on Aging and Care in Kungsholmen, who underwent repeated neuropsychological testing (episodic memory, semantic memory, verbal fluency, perceptual speed) across 12 years. The LS7 score, assessed at baseline, included smoking, diet, physical activity, body mass index, plasma glucose, total cholesterol, and blood pressure. Preclinical dementia was defined as being dementia-free at baseline and diagnosed with dementia during follow-up. Level and change in cognitive performance as a function of LS7 category (poor vs. intermediate to optimal) and future dementia status were estimated using linear mixed-effect models. Results: Participants who later developed dementia had, on average, a poorer LS7 score compared to those who remained dementia-free. For individuals aged 60-72 years, poor diet was associated with accelerated decline in perceptual speed (beta = -0.05, 95% CI [-0.08, -0.02]), and a poor glucose score was associated with faster rates of verbal fluency (beta = -0.019, 95% CI [-0.09, -0.01]) and global cognitive (beta = -0.028, 95% CI [-0.06, 0.00]) decline in the preclinical dementia group. Conclusions: VRFs exacerbate rate of cognitive decline in the years preceding a dementia diagnosis. This effect was most pronounced in young-old age and primarily driven by diet and glucose. The effect of VRFs may be especially detrimental for cognitive decline trajectories of individuals with impending dementia.

A common concern for patients with dementia is the time until severe stages and mortality. Current literature is sparce and often features small sample sizes. We aim to determine the time spent in mild cognitive impairment (MCI), mild-, moderate-, or severe dementia, institutionalization, and death. Multistate modeling was used to obtain the time in each state. Covariates were age at study baseline, sex, amyloid status, and Alzheimer’s disease (AD) diagnosis. The sample included a register (SveDem) and memory clinics (Amsterdam Dementia Center and Memento). Based on 80,972 patients, the full disease course from MCI to institutionalized-severe dementia lasted between 7.91 (95% CI: 7.07-9.02) years for males aged 87 at baseline and 11.70 (9.96–14.44) years for females aged 71. Generally, rapid progression was associated with older age at baseline, males, and AD diagnosis. The results provide key estimates for researchers and clinicians to estimate prognosis.

Samostojna vožnja avtomobila posamezniku omogoča neodvisnost in dejavno vključenost v družbo. Predstavlja kompleksno dejavnost, ki zahteva uporabo kognitivnih, senzoričnih in motoričnih sposobnosti voznika. Naraščajoči delež starejših v Sloveniji, tako kot v ostalih delih razvitega sveta, pomeni, da se bo v bližnji prihodnosti pomembno povečalo tudi število oseb z nevrodegenerativnimi boleznimi, najpogostejši med njimi sta Alzheimerjeva bolezen in Parkinsonova bolezen. Čeprav starejši povzročijo razmeroma malo prometnih nezgod, se to najverjetneje povezuje s pogostostjo njihove udeležbe v prometu. Upoštevajoč število prevoženih kilometrov so starejši ena od starostnih skupin, ki povzroči največ prometnih nesreč. Pri bolnikih z napredovalo demenco pa so sposobnosti vožnje še dodatno poslabšane, učinkovitost strategij kompenzacije vožnje (npr. izogibanje vožnji ponoči in vožnji po avtocesti) pa vprašljiva. Raziskave o vozniški uspešnosti posameznikov v začetni fazi demence niso povsem enoznačne, zato se o vozniški sposobnosti ne smemo odločati le na osnovi diagnoze. Potrebna je individualna skrbna analiza kliničnega stanja in dodatnih podatkov, dobljenih z nevropsihološkimi testi in preizkusno vožnjo. Ključno je upoštevanje posebnosti nevroloških in drugih okvar pri posameznih boleznih ter možnosti kompenzacije okrnjenih sposobnosti. Glede na široko paleto dejavnikov, ki vplivajo na oceno vozniške zmožnosti, enoznačnega priporočila o vozniški zmožnosti ob postavitvi diagnoze demenca ali parkinsonizem ni moč podati.

INTRODUCTION:Inferring the timeline from mild cognitive impairment (MCI) to severe dementia is pivotal for patients, clinicians, and researchers. Literature is sparse and often contains few patients. We aim to determine the time spent in MCI, mild-, moderate-, severe dementia, and institutionalization until death. METHODS:Multistate modeling with Cox regression was used to obtain the sojourn time. Covariates were age at baseline, sex, amyloid status, and Alzheimer's disease (AD) or other dementia diagnosis. The sample included a register (SveDem) and memory clinics (Amsterdam Dementia Cohort and Memento). RESULTS:Using 80,543 patients, the sojourn time from clinically identified MCI to death across all patient groups ranged from 6.20 (95% confidence interval [CI]: 5.57-6.98) to 10.08 (8.94-12.18) years. DISCUSSION:Generally, sojourn time was inversely associated with older age at baseline, males, and AD diagnosis. The results provide key estimates for researchers and clinicians to estimate prognosis.

We investigated whether vascular risk factors (VRFs), assessed with the Life’s Simple 7 (LS7) score, are associated with rate of cognitive decline in the preclinical dementia phase. We sought to test whether (1) poor LS7 further accelerates rate of cognitive decline in preclinical dementia or (2) the dementia process itself overshadows potential effects of LS7. This population-based study included 1,449 participants aged ≥ 60 years (M = 69.99, SD = 9.25) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K). Participants aged < 78 years at baseline (M = 65.03) were categorised into a young-old group and those ≥ 78 years (M = 82.61) into an old-old group. An extensive cognitive test battery (episodic memory, semantic memory, verbal fluency, and perceptual speed) was administered across 12 years. VRFs were assessed with the Life’s Simple 7 (LS7) score at baseline and included four behavioral (smoking, diet, physical activity, and body mass index) and three biological (plasma glucose, total serum cholesterol, and blood pressure) metrics. Participants were categorised into having poor or intermediate/optimal cardiovascular health. Preclinical dementia was defined as being dementia-free at baseline and diagnosed with dementia (DSM-IV criteria) at one of the follow-up assessments. Level and change in cognitive performance as a function of LS7 categories and future dementia status were determined using linear mixed-effects models. Participants in a preclinical dementia phase were more likely to have a poorer LS7 score initially compared to those who remained dementia-free (p = 0.023). For young-old individuals, poor diet was associated with an accelerated perceptual speed decline (β = -0.05, 95% CI -0.08 to -0.02) and a poor plasma glucose score was associated with faster rates of verbal fluency (β = -0.019, -0.09 to -0.01) and global cognitive (β = -0.028, -0.06 to 0.00) decline in preclinical dementia. The association between VRFs and cognitive decline was most pronounced in young-old individuals in a preclinical phase of dementia and driven mostly by diet and plasma glucose. Poor cardiovascular health may be associated with further acceleration of cognitive decline in preclinical dementia.

Background and ObjectiveThe life's simple 7 approach was proposed to define cardiovascular health (CVH) metrics. We sought to investigate the associations between behavioral, biological, and genetic markers for CVH and vascular brain aging in older adults.MethodsThis population-based cohort study included participants who had repeated brain MRI measures from 2001 to 2003 to 2007-2010 (i.e., count of perivascular spaces, volumes of white matter hyperintensity [WMH] and gray matter, and lacunes). At baseline, global, behavioral, and biological CVH metrics were defined and scored following the life's simple 7 approach and categorized into unfavorable, intermediate, and favorable profiles according to tertiles. The metabolic genetic risk score was calculated by counting 15 risk alleles associated with hypertension, diabetes, or dyslipidemia. Data were analyzed using linear mixed-effects and Cox proportional hazards models, adjusting for age, sex, and education.ResultsThe study sample consisted of 317 participants (age 60 years or older; 61.8% women). Favorable and intermediate (vs unfavorable) global CVH profiles were related to slower WMH progression, with beta-coefficients (95% CI) being -0.019(-0.035-0.002) and -0.018(-0.034-0.001), respectively. Favorable and intermediate (vs unfavorable) biological CVH profiles were significantly related to slower WMH increase only in people aged 60-72 years. CVH profiles were not related to progression of other brain measures. Furthermore, a higher metabolic genetic risk score (range: 6-21) was associated with faster WMH increase (beta-coefficient = 0.005; 95% CI: 0.003-0.008). There were statistical interactions of metabolic genetic risk score with global and behavioral CVH profiles on WMH accumulation. A higher metabolic genetic risk score was related to faster WMH accumulation, with beta-coefficients being 0.015(0.007-0.023), 0.005(0.001-0.009), and 0.003(-0.001 to 0.006) among people with unfavorable, intermediate, and favorable global CVH profiles, respectively; the corresponding beta-coefficients were 0.013(0.006-0.020), 0.006(0.003-0.009), and 0.002(-0.002 to 0.006) among people with unfavorable, intermediate, and favorable behavioral CVH profiles.DiscussionIntermediate to favorable global CVH profiles in older adults are associated with slower vascular brain aging. The association of metabolic genetic risk load with accelerated vascular brain aging was evident among people with unfavorable to intermediate, but not favorable, CVH profiles. These findings highlight the importance of adhering to favorable CVH profiles, especially healthy behaviors, in vascular brain health.

Background: Modifiable vascular risk factors have been associated with late-life cognitive impairment. The Life Simple 7 (LS7) score comprises seven cardiovascular health metrics: smoking, diet, physical activity, body mass index, plasma glucose, total serum cholesterol, and blood pressure. Objective: To investigate the association between individual and composite LS7 metrics and rate of cognitive decline, and potential differences in these associations between young-old and old-old individuals. Methods: This cohort study included 1,950 participants aged≥60 years (M = 70.7 years) from the Swedish National Study on Aging and Care-Kungsholmen (SNAC-K), who underwent repeated neuropsychological testing (episodic and semantic memory, verbal fluency, processing speed, global cognition) across 12 years. The LS7 score was assessed at baseline and categorized as poor, intermediate, or optimal. Level and change in cognitive performance as a function of LS7 categories were estimated using linear mixed-effects models. Results: Having an optimal LS7 total score was associated with better performance (expressed in standard deviation units) at baseline for perceptual speed (β= 0.21, 95%CI 0.12–0.29), verbal fluency (β= 0.08, 0.00–0.16), and global cognition (β= 0.06, 0.00–0.12) compared to the poor group. Age-stratified analyses revealed associations for cognitive level and change only in the young-old (< 78 years) group. For the specific metrics, diverging patterns were observed for young-old and old-old individuals. Conclusion: Meeting the LS7 criteria for ideal cardiovascular health in younger old age is associated with slower rate of cognitive decline. However, the LS7 criteria may have a different meaning for cognitive function in very old adults.

AbstractBackgroundThe presence of cardiovascular risk factors leads to negative consequences in old age. To promote the intervention of such risk factors, the American Heart Association defined a metric of ideal cardiovascular health, also referred to as Life’s Simple 7 (LS7). The adherence to the LS7 recommendations has previously been linked to a lower risk of dementia and cognitive decline. The objective of this study was to investigate the association between individual and composite cardiovascular health metrics and rate of cognitive decline in an older population‐based sample.MethodParticipants aged ≥60 years from the Swedish National Study on Aging and Care‐Kungsholmen underwent repeated neuropsychological testing across 12 years. Domain specific scores were calculated for episodic memory, semantic memory, verbal fluency, and processing speed. The LS7 score, assessed at baseline, was composed of four behavioral (smoking, body mass index, diet, and physical activity) and three biological (serum total cholesterol, plasma glucose, and blood pressure) metrics. All metrics were categorized into three levels (poor = 0, intermediate = 1, and optimal = 2), where the LS7 total score was the sum of seven metrics (range 0‐14). On the basis of tertiles, it was categorized into poor (scores 0‐6), intermediate (7‐9) and optimal (10‐14). Data were analyzed with linear mixed‐effects models.ResultAmong 1828 participants with data on LS7 (mean age 70.4; 60.8% women), nobody achieved optimal levels for all 7 metrics. The average total score was 7.7 (SD = 1.9) and participants were classified as having poor (26.3%), intermediate (55.6%), or optimal (18.2%) cardiovascular health. People belonging to the intermediate or optimal group of cardiovascular health showed higher levels of cognitive performance. Although a more ideal level on specific metrics (e.g. blood pressure) was significantly associated with slower rates of cognitive decline, we observed no significant associations of the composite cardiovascular health metric with rate of cognitive change.ConclusionIn this cohort study, a composite score of cardiovascular health (LS7) did not predict rate of cognitive decline. Ideal cardiovascular health in specific metrics, however, was associated with slower decline rates. Further analyses of subgroups and interaction effects are ongoing.