Comparative assessment of donepezil memantine and sodium oligomannate on cognitive decline and neuroinflammation in early Alzheimer's disease.

The Alzheimer's Disease Assessment Scale - Cognitive Subscale is a brief battery developed to assess cognitive functioning in Alzheimer's disease that encompasses the core characteristics of cognitive decline (e.g. memory, language, praxis, constructive ability and orientation). The early detection, as well as the monitoring of cognitive decline along disease progression, is extremely important in clinical care and interventional research. The main goals of the present study were to analyze the psychometric properties of the Portuguese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale, and to establish normative values for the Portuguese population. The Portuguese version of Alzheimer's Disease Assessment Scale - Cognitive Subscale was administered to 223 cognitively healthy participants according to a standard assessment protocol consisting of the Mini-Mental State Examination, the Montreal Cognitive Assessment and the Adults and Older Adults Functional Assessment Inventory. Normal performance on the assessment protocol was the inclusion criteria for the study. The Alzheimer's Disease Assessment Scale - Cognitive Subscale revealed good psychometric properties when used in the Portuguese population. Age was the main predictor of the Alzheimer's Disease Assessment Scale - Cognitive Subscale total score (R2 = 0.123), whereas the influence of education level was lower (R2 = 0.027). These two variables explained 14.4% of the variance on the Alzheimer's Disease Assessment Scale - Cognitive Subscale scores and were used to stratify the normative values for the Portuguese population presented here. On the total sample, the average total score in the Alzheimer's Disease Assessment Scale - Cognitive Subscale was 6 points. The normative data were determined according to age and educational level as these were the sociodemographic variables that significantly contributed to the prediction of the Alzheimer's Disease Assessment Scale - Cognitive Subscale total scores, explaining 14.4% of their variance. The normative data are of the utmost importance to ensure proper use of this battery in Portugal.

Longitudinal Exposure-Response Modeling of Multiple Indicators of Alzheimer's Disease Progression.

Comparative and combined accuracies of objective versus subjective screening instruments in distinguishing Alzheimer’s disease, mild cognitive impairment, and age-related cognitive decline

PL‐03‐02: Evaluating semagacestat, a gamma‐secretase inhibitor, in a phase III trial

Impaired Awareness of Deficits and Neuropsychiatric Symptoms in Early Alzheimer's Disease: The Danish Alzheimer Intervention Study (DAISY)

The approved amyloid antibodies for early Alzheimer's disease (AD) carry a boxed warning about the risk of amyloid-related imaging abnormalities (ARIAs) that are highest in apolipoprotein E (APOE) ε4/ε4 homozygotes. ALZ-801/valiltramiprosate, an oral brain-penetrant amyloid beta oligomer inhibitor is being evaluated in APOE ε4/ε4 homozygotes with early AD. This Phase 3 randomized, double-blind, placebo-controlled, 78-week study of ALZ-801 administered as 265mg twice per day tablets, enrolled 50- to 80-year-old homozygotes with Mini-Mental State Examination (MMSE) ≥ 22 and Clinical Dementia Rating-Global Score 0.5 or 1.0. The study is powered to detect a 2.0 to 2.5 drug-placebo difference on the Alzheimer's Disease Assessment Scale 13-item Cognitive subscale primary outcome with 150 subjects/arm. The key secondary outcomes are Clinical Dementia Rating-Sum of Boxes and Instrumental Activities of Daily Living; volumetric magnetic resonance imaging and fluid biomarkers are additional outcomes. The APOLLOE4 Phase 3 trial enrolled 325 subjects with a mean age of 69 years, 51% female, MMSE 25.6, and 65% mild cognitive impairment. Topline results are expected in 2024. APOLLOE4 is the first disease-modification AD trial focused on APOE ε4/ε4 homozygotes. Oral ALZ-801 has the potential to be the first effective and safe anti-amyloid treatment for the high-risk APOE ε4/ε4 population. The APOLLOE4 Phase 3, placebo-controlled, 78-week study is designed to evaluate the efficacy and safety of ALZ-801 265mg twice per day in early Alzheimer's disease (AD) subjects with the apolipoprotein E (APOE) ε4/ε4 genotype.The enrolled early AD population (N=325) has 51% females, a mean age = 69 years, and a mean Mini-Mental State Examination = 25.6, with the majority being mild cognitive impairment subjects, a similar disease stage to the lecanemab Phase 3 AD trial (Clarity AD).The primary outcome is the cognitive Alzheimer's Disease Assessment Scale 13-item Cognitive subscale, with two functional measures as key secondary outcomes (Clinical Dementia Rating-Sum of Boxes, Amsterdam-Instrumental Activities of Daily Living), and with hippocampal volume and fluid biomarkers as additional outcomes.The study is unique in allowing a large number of microhemorrhages or siderosis at baseline magnetic resonance imaging, lesions that indicate concomitant cerebral amyloid angiopathy (CAA).At baseline, 32% of the enrolled population had at least 1 microhemorrhage, 24% had 1 to 4, and 8% had > 4 microhemorrhages; 10% had at least 1 siderosis lesion; with more males than females having microhemorrhages (63% vs. 37%) and siderosis (68% vs. 32%).Study results will become available in the second half of 2024 and, if positive, ALZ-801 may become the first oral drug to demonstrate a favorable benefit/risk profile in APOE ε4/ε4 AD subjects.

To report the psychometric properties of an alternative instrument to the cognitive subscale of the Alzheimer's Disease Assessment Scale, a neuropsychological test battery (NTB) for measuring drug efficacy in Alzheimer disease clinical trials. The NTB was evaluated in a randomized, double-blind, placebo-controlled trial of AN1792(QS-21) (synthetic beta-amyloid plus an adjuvant) (300 patients) and isotonic sodium chloride solution (72 patients). The test-retest reliability of the NTB was examined, and the NTB was correlated with other cognitive (cognitive subscale of the Alzheimer's Disease Assessment Scale and Mini-Mental State Examination) and functional (Disability Assessment Scale for Dementia and Clinical Dementia Rating Sum of Boxes) measures. In addition, a factor analysis was performed on NTB components. Finally, the sensitivity of the NTB to change was assessed as a function of Mini-Mental State Examination performance. The NTB had high test-retest reliability at 6 (Pearson product moment correlation [r] = 0.92) and 12 (r = 0.88) months. Internal consistency was high (Cronbach alpha = 0.84). The correlations between the NTB z score and scores on traditional measures of cognition and function were significantly different from 0 (P < .001). A factor analysis yielded "memory" and "executive function" factors. The NTB z score declined linearly over 1 year in patients receiving placebo and, in contrast to the Alzheimer's Disease Assessment Scale cognitive subscale, demonstrated similar declines in patients with high (21-26) and low (15-20) Mini-Mental State Examination scores at baseline. The NTB exhibits excellent psychometric properties and seems to be a reliable and sensitive measure of cognitive change in patients with mild to moderate Alzheimer disease. The psychometric properties of the NTB suggest that it may have particular utility in evaluating drug efficacy in clinical trials in which patients with mild Alzheimer disease are included.

The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD, β-amyloid protein (Aβ) is deposited in the form of extracellular plaques and previous studies have determined Aβ generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction, it is biologically plausible they may be efficacious in the treatment of AD and VaD. To assess the clinical efficacy and safety of statins in the treatment of AD and VaD. To evaluate if the efficacy of statins in the treatment of AD and VaD depends on cholesterol level, ApoE genotype or cognitive level. We searched ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (20 January 2014). Double-blind, randomised controlled trials of statins given for at least six months in people with a diagnosis of dementia. Two independent authors extracted and assessed data against the inclusion criteria. We pooled data where appropriate and entered them into a meta-analysis. We used standard methodological procedures expected by The Cochrane Collaboration. We identified four studies (1154 participants, age range 50 to 90 years). All participants had a diagnosis of probable or possible AD according to standard criteria and most participants were established on a cholinesterase inhibitor. The primary outcome in all studies was change in Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) from baseline. When we pooled data, there was no significant benefit from statin (mean difference -0.26, 95% confidence interval (CI) -1.05 to 0.52, P value = 0.51). All studies provided change in Mini Mental State Examination (MMSE) from baseline. There was no significant benefit from statins in MMSE when we pooled the data (mean difference -0.32, 95% CI -0.71 to 0.06, P value = 0.10). Three studies reported treatment-related adverse effects. When we pooled data, there was no significant difference between statins and placebo (odds ratio 1.09, 95% CI 0.58 to 2.06, P value = 0.78). There was no significant difference in behaviour, global function or activities of daily living in the statin and placebo groups. We assessed risk of bias as low for all studies. We found no studies assessing role of statins in treatment of VaD. Analyses from the studies available, including two large randomised controlled trials, indicate that statins have no benefit on the primary outcome measures of ADAS-Cog or MMSE.

The use of statin therapy in established Alzheimer's disease (AD) or vascular dementia (VaD) is a relatively unexplored area. In AD ss-amyloid protein (Ass) is deposited in the form of extracellular plaques and previous studies have determined Ass generation is cholesterol dependent. Hypercholesterolaemia has also been implicated in the pathogenesis of VaD. Due to the role of statins in cholesterol reduction it is biologically plausible they may be efficacious in the treatment of AD and dementia. To assess the clinical efficacy and tolerability of statins in the treatment of dementia. We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (27 October 2008). Double-blind, randomized controlled trials of statins given for at least six months in people with a diagnosis of dementia. Two independent authors extracted and assessed data independently against the inclusion criteria. Data were pooled where appropriate and entered into a meta-analysis. Three studies were identified (748 participants, age range 50-90 years). All patients had a diagnosis of probable or possible AD according to standard criteria and most patients were established on a cholinesterase inhibitor. Treatment in ADCLT 2005 consisted of 80mg atorvastatin compared to placebo for 52 weeks, serum low density lipoprotein (LDL) cholesterol was reduced by 54% in the atorvastatin group. Treatment in Simons 2002 consisted of 40mg simvastatin compared to placebo for 26 weeks, serum LDL cholesterol was reduced by 52% in the simvastatin group. Treatment in LEADe 2010 consisted of 80mg atorvastatin compared to placebo for 72 weeks, LDL cholesterol was reduced by 50.2% by month 3 and remained constant through month 18. Change in Alzheimer's Disease Assessment Scale- cognitive subscale (ADAS-Cog) from baseline was a primary outcome in 3 studies; when data were pooled there was considerable heterogeneity so the random effects model was used, statins did not provide any beneficial effect in this cognitive measure [mean difference -1.12, 95% CI -3.99, 1.75, p = 0.44]. All studies provided change in Mini Mental State Examination (MMSE) from baseline; again random effects model was used due to considerable heterogeneity: there was no significant benefit from statins in this cognitive measure when the data were pooled [mean difference -1.53, 95% CI -3.28, 0.21, p = 0.08]. There was some evidence that patients on statins in ADCLT 2005 maintained better cognitive function if serum cholesterol was high at baseline, MMSE was higher at baseline or if they had an apolipoprotein E4 allele present. This would need to be confirmed in larger studies however. Treatment related adverse effects were available from two studies, LEADe 2010 and Simons 2002; when data were pooled there was no significant difference between statins and placebo [odds ratio 2.45, 95% CI 0.69, 8.62, p = 0.16]. There was no significant difference in global function, behaviour or activities of daily living in the statin and placebo groups. One large randomised controlled trial (RCT) ( CLASP 2008) has not yet published its results. There were no studies identified assessing role of statins in treatment of VaD. There was no evidence that statins were detrimental to cognition. There is insufficient evidence to recommend statins for the treatment of dementia. Analysis from the studies available, including one large RCT, indicate statins have no benefit on the outcome measures ADAS-Cog or MMSE. We need to await full results from CLASP 2008 before we can be certain. This Cochrane review will be updated as these results become available.

IntroductionDespite significant progress, a disease-modifying therapy for Alzheimer’s disease (AD) has not yet been developed. Recent findings implicate soluble oligomeric amyloid beta as the most relevant protein conformation in AD pathogenesis. We recently described a signaling cascade whereby oligomeric amyloid beta binds to cellular prion protein on the neuronal cell surface, activating intracellular Fyn kinase to mediate synaptotoxicity. Fyn kinase has been implicated in AD pathophysiology both in in vitro models and in human subjects, and is a promising new therapeutic target for AD. Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD.MethodsThe study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26. A total of 24 subjects were recruited in three sequential groups, with each randomized to receive oral AZD0530 at doses of 50 mg, 100 mg, 125 mg, or placebo daily for 4 weeks. The drug:placebo ratio was 3:1. Primary endpoints were safety, tolerability, and cerebrospinal fluid (CSF) penetration of AZD0530. Secondary endpoints included changes in clinical efficacy measures (Alzheimer’s Disease Assessment Scale – cognitive subscale, MMSE, Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory, Neuropsychiatric Inventory, and Clinical Dementia Rating Scale – Sum of Boxes) and regional cerebral glucose metabolism measured by fluorodeoxyglucose positron emission tomography.ResultsAZD0530 was generally safe and well tolerated across doses. One subject receiving 125 mg of AZD0530 was discontinued from the study due to the development of congestive heart failure and atypical pneumonia, which were considered possibly related to the study drug. Plasma/CSF ratio of AZD0530 was 0.4. The 100 mg and 125 mg doses achieved CSF drug levels corresponding to brain levels that rescued memory deficits in transgenic mouse models. One-month treatment with AZD0530 had no significant effect on clinical efficacy measures or regional cerebral glucose metabolism.ConclusionsAZD0530 is reasonably safe and well tolerated in patients with mild-to-moderate AD, achieving substantial central nervous system penetration with oral dosing at 100–125 mg. Targeting Fyn kinase may be a promising therapeutic approach in AD, and a larger Phase IIa clinical trial of AZD0530 for the treatment of patients with AD has recently launched.Trial registrationClinicalTrials.gov: NCT01864655. Registered 12 June 2014.

Studies targeting amyloid-ß in patients with Alzheimer's disease (AD) have conflicting results and early initiation of therapy may yield better outcomes. We systematically searched PubMed, Embase, Cochrane Library, and Clinicaltrials.gov for randomized trials comparing monoclonal antibodies (mAbs) with placebo in MCI or mild dementia due to AD. Nineteen studies comprising 15,275 patients were included. In patients with early AD, mAbs reduced the rate of decline, in both the Clinical Dementia Rating Scale, the sum of boxes (CDR-SB; MD -0.30; 95% CI -0.42,-0.19; p < 0.01), and the Alzheimer's Disease Assessment Scale, cognitive subscore (ADAS-cog; SMD -0.80; 95% CI -10.25,-0.35; p < 0.01). The results were similar between clinical stages for CDR-SB (MCI, MD -0.19; 95% CI -0.35,-0.03; p = 0.02; mild dementia, MD -0.45; 95% CI -0.65,-0.25; p < 0.01; subgroup differences, p = 0.13), as well as for ADAS-Cog (MCI, SMD -0.83; 95% CI -1.49,-0.17; p = 0.01; mild dementia, SMD -0.69; 95% CI -1.32 to -0.05; p = 0.03; subgroup differences, p = 0.47). The risk of amyloid-related imaging abnormalities (ARIA) was significantly higher in patients taking mAbs, including ARIA-edema (RR 7.7; 95% CI 4.60 to 13.00; p < 0.01), ARIA-hemorrhage (RR 1.8; 95% CI 1.22 to 2.59; p < 0.01), and symptomatic or serious ARIA (RR 14.1; 95% CI 7.30 to 27.14; p < 0.01). Anti-amyloid-ß mAbs attenuate cognitive and functional decline compared with placebo in early AD; whether the magnitude of this effect is clinically important remains uncertain, especially relative to the safety profile of these medications. Starting immunotherapy in patients with MCI was not significantly different than starting in the mild dementia stage. CRD42023430698.

Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer's disease.

There is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials. To agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI). We included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches. The project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes. We included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally. Most of the trials included participants with Alzheimer's disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimer's Society Research Network. Cognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants. We envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog. The project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346. The National Institute for Health Research Health Technology Assessment programme.

SUMMARYObjectives: To evaluate the safety and efficacy of long-term treatment with rivastigmine (3–12 mg/day) and its effects on neuropsychiatric and behavioral disturbances in nursing home patients with moderate to severe probable Alzheimer's disease (AD).Methods: A prospective, multicenter 26-week open-label extension to a 26-week open-label study (52 week results) of rivastigmine treatment in patients with Mini-Mental State Examination (MMSE) scores of 6–15 inclusive, residing in nursing homes at 13 centers in the US. Effects of treatment with rivastigmine for up to 52 weeks on neuropsychiatric and behavioral symptoms were examined using the Neuropsychiatric Inventory-Nursing Home (NPI-NH) scale. Cognitive function was assessed by the MMSE, and the Naming Objects and Fingers Test (NOFT) subset of the Alzheimer's Disease Assessment Scale – Cognitive subscale (ADAS-Cog). Global functioning was assessed using the simplified Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus).Results: Rivastigmine (3–12 mg/day) significantly improved neuropsychiatric and behavioral symptoms compared to baseline (in patients with specific behavioral disturbances at baseline) in observed cases (OC) and last observation carried forward (LOCF) analyses. Over 52 weeks, treatment with rivastigmine significantly improved 10 of 12 individual NPI-NH domains from baseline in LOCF patients with symptoms present at baseline. Cognitive function was stable, indicated by the lack of decline in MMSE and the NOFT. Global function was stabilized or improved in greater than half of the patients as indicated by the simplified CIBIC-Plus scores.Conclusion: Rivastigmine showed potential benefit in the long-term treatment of behavioral symptoms as well as cognitive and global functioning in nursing home residents with moderate to severe AD with concurrent behavioral symptoms present at baseline. Although these results suggest that treatment with rivastigmine may have beneficial behavioral effects and cognitive benefits on patients with moderate to severe AD, they are subject to the limitations of an open-label study.

BACKGROUND: Increasing life expectancy is closely related to the increasing burden of polymorbidity, as well as the number of medications per patient of elderly and senile age (polypharmacy). These factors can have a direct and indirect impact on the cognitive and functional status of patients, which is of utmost importance for preserving both, the duration and the quality of life of older patients. AIM: Assessment of functional status of multimorbid elderly patients with essential arterial hypertension depending on the burden and structure of multimorbidity and its possible relationship with cognitive function condition. METHODS: 330 patients aged ≥ 60 years with arterial hypertension (median age 79 years, 50.6% women) were included in the study. All patients underwent assessment of functional status using the Functional Activities Questionnaire (FAQ) and cognitive functions using the Montreal Cognitive Assessment Scale, Mini-Mental State Examination, Alzheimer’s Disease Assessment Scale (Cognitive Subscale). RESULTS: The median total score on the FAQ questionnaire was statistically significantly higher in the atrial fibrillation group [12 (9–14) points] compared to the arterial hypertension group without atrial fibrillation [10 (6–12) points; p = 0.001], in the chronic kidney disease group [11 (8–14) points] than in the group without chronic kidney disease [10 (6–13) points; p = 0.002). The median final FAQ questionnaire score was statistically significantly (p 0.001) higher in the group of patients with a Charlson comorbidity index ≥ 8 points [12 (9–15) points] compared to that in the group of patients with a Charlson index score of 0–4 points [9 (6–11) points]. According to linear regression analysis, there was a statistically significant relationship between the number of FAQ scores, on the one hand, and the patients’ age (R2 = 0.175; β = 0.422), Charlson comorbidity index (R2 = 0.044; β = 0.216), and the results of cognitive functions testing [Mini-Mental State Examination (R2 = 0.348; β = −0.591), Montreal Cognitive Assessment Scale (R2 = 0.286; β = −0.537), Alzheimer’s Disease Assessment Scale (Cognitive Subscale; R2 = 0.345; β = 0.589; p 0.001 in all cases). CONCLUSION: In elderly patients with essential arterial hypertension, the presence of concomitant atrial fibrillation and chronic kidney disease has a negative impact on their functional activity and cognitive status. Decrease in functional activity and deterioration of cognitive functioning of elderly patients with arterial hypertension is also associated with increasing age and burden of multimorbidity (Charlson index).