scholarly journals Affective Neuropsychiatric Symptoms as Early Signs of Dementia Risk in Older Adults

2020 ◽  
Vol 77 (3) ◽  
pp. 1195-1207
Author(s):  
Jung Yun Jang ◽  
Jean K. Ho ◽  
Anna E. Blanken ◽  
Shubir Dutt ◽  
Daniel A. Nation ◽  
...  

Background: Affective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability) have been linked to increased dementia risk. However, less is known whether this association is independent of Alzheimer’s disease (AD) pathophysiology. Objective: To investigate the contribution of early aNPS to dementia risk in cognitively normal (CN) older adults and mild cognitive impairment (MCI) patients, with and without AD biomarker abnormality. Methods: Participants included 763 community-dwelling, stroke-free older adults identified as CN and 617 with MCI at baseline, drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Baseline assessments included a neuropsychological battery, the Neuropsychiatric Inventory (NPI), and apolipoprotein E ɛ4 (ApoE4) genotyping. A participant subset completed cerebrospinal fluid (CSF) AD biomarker assessment. Time to progression to dementia was measured based on months at follow-up when an individual was diagnosed with dementia, over the follow-up period of 48 months. Results: Latent class analysis identified 3 subgroups of older adults in CN and MCI, indicated by the baseline profiles of neuropsychiatric symptoms (NPS). Subgroups with higher aNPS were at increased risk of progression to dementia in both CN (HR = 3.65, 95% CI [1.80, 7.40]) and MCI (HR = 1.52, 95% CI [1.16, 2.00]; HR = 1.86 [1.05, 3.30]) groups, adjusting for age, sex, global cognition, and ApoE4, compared with their counterparts with minimal NPS. There was no difference between higher aNPS and minimal NPS subgroups in their CSF AD biomarker profiles. Conclusion: Findings suggest that aNPS may represent a neurobiological vulnerability that uniquely contribute to the dementia risk, independent of AD biomarker profiles.

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S971-S971
Author(s):  
Jung Y Jang ◽  
Daniel A Nation

Abstract The current study sought to investigate the association between affective neuropsychiatric symptoms (aNPS: depression, anxiety, apathy, irritability), Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers profiles, and the risk of progression to dementia in non-demented older adults. Participants consisted of 763 individuals with normal cognition (CN) (mean age = 73.73 ± 6.68) and 617 with mild cognitive impairment (MCI) (mean age = 73.19 ± 7.40) at baseline, who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Latent class analyses (LCA) identified three subgroups of older adults within CN and MCI, respectively, showing distinct patterns of the neuropsychiatric inventory (NPI) domains. Results indicated that the subgroup with higher probabilities of aNPS had elevated risk of progression to dementia (HR = 3.18, 95% CI [1.70, 5.94] in CN, HR = 1.79, 95% CI [1.01, 3.16] in MCI), adjusting for age, sex, and Apolipoprotein E e4 (APOE4) carrier status. Subgroups did not differ in their profiles of AD CSF biomarkers. Findings suggest that aNPS might be symptoms of secondary disease processes in the brain, lowering the threshold for AD pathophysiology to manifest clinically in CN and MCI. The current study highlights the importance of assessment and interventions for emotional and behavioral symptoms in non-demented older adults.


2006 ◽  
Vol 35 (3) ◽  
pp. 308-310 ◽  
Author(s):  
Maria E. Soto ◽  
Sandrine Andrieu ◽  
Sophie Gillette-Guyonnet ◽  
Christelle Cantet ◽  
Fati Nourhashemi ◽  
...  

2020 ◽  
Vol 77 (1) ◽  
pp. 175-182
Author(s):  
Eric D. Vidoni ◽  
Ashwini Kamat ◽  
William P. Gahan ◽  
Victoria Ourso ◽  
Kaylee Woodard ◽  
...  

Background: Little is known about the prevalence of polypharmacy, the taking of five or more medications a day, in older adults with specific dementia risk factors. Objective: To examine the prevalence of polypharmacy in participants at baseline in a vascular risk reduction focused Alzheimer’s disease (rrAD) trial targeting older patients with hypertension and elevated dementia risk. Methods: We conducted a detailed review of medications in a cross-sectional study of community-dwelling older adults with hypertension and elevated dementia risk. Medications were identified in a structured interview process with an onsite pharmacist or qualified designee. Polypharmacy was defined as use of five or more medications on a regular basis. Descriptive analyses were conducted on the sample as well as direct comparisons of subgroups of individuals with hypertension, diabetes, and hyperlipidemia. Results: The 514 rrAD participants, mean age 68.8 (standard deviation [sd] 6), reported taking different combinations of 472 unique medications at their baseline visit. The median number of medications taken by participants was eight [Range 0–21], with 79.2% exhibiting polypharmacy (n = 407). Sites differed in their prevalence of polypharmacy, χ2(3) = 56.0, p < 0.001. A nearly identical percentage of the 2,077 prescribed (51.8%) and over the counter (48.2%) medications were present in the overall medication profile. The presence of diabetes (87.5%), hyperlipidemia (88.2%), or both (97.7%) was associated with a higher prevalence of polypharmacy than participants who exhibited hypertension in the absence of either of these conditions (63.2%), χ2(3) = 35.8, p < 0.001. Conclusion: Participants in a dementia risk study had high levels of polypharmacy, with the co-existence of diabetes or hyperlipidemia associated with a greater prevalence of polypharmacy as compared to having hypertension alone.


2017 ◽  
Vol 44 (5-6) ◽  
pp. 259-265 ◽  
Author(s):  
Hannes Holm ◽  
Katarina Nägga ◽  
Erik D. Nilsson ◽  
Fabrizio Ricci ◽  
Eduardo Cinosi ◽  
...  

Background: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults. Methods: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke. Results: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values. Conclusions: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.


2017 ◽  
Vol 51 (9) ◽  
pp. 725-734 ◽  
Author(s):  
Virva Hyttinen ◽  
Heidi Taipale ◽  
Anna-Maija Tolppanen ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
...  

Background: Potentially inappropriate medications (PIMs) increase the risk of adverse drug reactions and events and have been associated with greater health care service use, such as an increased risk of hospitalization. Objective: The aim of this study is to evaluate the association between PIM use and hip fractures in a nationwide cohort of community-dwelling persons ≥65 years old with Alzheimer’s disease (AD). Methods: The study, which is based on the Finnish nationwide MEDALZ cohort, included all persons diagnosed with AD between 2005 and 2011 (n = 70 718). After a 1-year washout period for PIM use and exclusion of persons with previous hip fracture before AD diagnosis or those who had been hospitalized, we included 47 850 persons ≥65 years old with AD. PIM use was identified using Finnish criteria. Associations between PIM use and hip fracture were analyzed with Cox proportional hazards regression. Results: Of the study population, 12.3% (n = 5895) initiated PIMs during the follow-up (maximum follow-up 2921 days and total number of person-years 139 538.7). Of those, 103 (1.7%) persons had hip fractures during the PIM use period. The results suggest that PIM use was only associated with an increased risk of hip fracture with incident PIM use (adjusted hazard ratio = 1.31; 95% CI = 1.06-1.63; P = 0.014). Conclusions: PIM use is associated with increased risk of hip fracture when a person uses PIMs for the first time. However, the association between PIM use and hip fracture should be investigated more comprehensively in future studies.


Author(s):  
Susan Greimel ◽  
Jean F Wyman ◽  
Lin Zhang ◽  
Fang Yu

Abstract Background Recruiting older adults with Alzheimer’s disease (AD) dementia into clinical trials is challenging requiring multiple approaches. We describe recruitment and screening processes and results from the FIT-AD Trial, a single site, pilot randomized controlled trial testing the effects of a 6-month aerobic exercise intervention on cognition and hippocampal volume in community-dwelling older adults with mild-to moderate AD dementia. Methods Ten recruitment strategies and a four-step screening process were used to ensure a homogenous sample and exercise safety. The initial target sample was 90 participants over 48 months which was increased to 96 to allow those in the screening process to enroll if qualified. A tertiary analysis of recruitment and screening rates, recruitment yields and costs, and demographic characteristics of participants was conducted. Results During the 48-month recruiting period, 396 potential participants responded to recruitment efforts, 301 individuals were reached and 103 were tentatively qualified. Of these, 67 (69.8%) participants completed the optional magnetic resonance (MRI) imaging and seven were excluded due to abnormal MRI findings. As a result, we enrolled 96 participants with a 2.92 screen ratio, 2.14 recruitment rate, and 31.9% recruitment yield. Referrals (28.1%) and Alzheimer’s Association events/services (21.9%) yielded over 49% of the enrolled participants. Total recruitment cost was $ 38,246 or $ 398 per randomized participant. Conclusions A multi-prong approach involving extensive community outreach was essential in recruiting older adults with AD dementia into a single-site trial. For every randomized participant, three individuals needed to be screened. Referrals were the most cost-effective recruitment strategy.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S641-S641
Author(s):  
Shanna L Burke

Abstract Little is known about how resting heart rate moderates the relationship between neuropsychiatric symptoms and cognitive status. This study examined the relative risk of NPS on increasingly severe cognitive statuses and examined the extent to which resting heart rate moderates this relationship. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform Data Set was undertaken, using observations from participants with normal cognition at baseline (13,470). The relative risk of diagnosis with a more severe cognitive status at a future visit was examined using log-binomial regression for each neuropsychiatric symptom. The moderating effect of resting heart rate among those who are later diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assessed. Delusions, hallucinations, agitation, depression, anxiety, elation, apathy, disinhibition, irritability, motor disturbance, nighttime behaviors, and appetite disturbance were all significantly associated (p&lt;.001) with an increased risk of AD, and a reduced risk of MCI. Resting heart rate increased the risk of AD but reduced the relative risk of MCI. Depression significantly interacted with resting heart rate to increase the relative risk of MCI (RR: 1.07 (95% CI: 1.00-1.01), p&lt;.001), but not AD. Neuropsychiatric symptoms increase the relative risk of AD but not MCI, which may mean that the deleterious effect of NPS is delayed until later and more severe stages of the disease course. Resting heart rate increases the relative risk of MCI among those with depression. Practitioners considering early intervention in neuropsychiatric symptomology may consider the downstream benefits of treatment considering the long-term effects of NPS.


2021 ◽  
Vol 80 (2) ◽  
pp. 749-759
Author(s):  
Albert Lladó ◽  
Lutz Froelich ◽  
Rezaul K. Khandker ◽  
Montserrat Roset ◽  
Christopher M. Black ◽  
...  

Background: There exists considerable variation in disease progression rates among patients with Alzheimer’s disease (AD). Objective: The primary objective of this observational study is to assess the progression of AD by characterizing cognitive, functional, and behavioral changes during the follow-up period between 6 and 24 months. Methods: A longitudinal prospective study with community-dwelling patients with an established clinical diagnosis of AD of mild to moderate severity was conducted in Germany, Spain and the UK. A sample of 616 patients from 69 sites was included. Results: Patients had a mean of 1.9 years (SD = 1.9) since AD diagnosis at study inclusion. Cognitive symptoms were reported to have first occurred a mean of 1.1 years (SD = 1.7) prior to AD diagnosis and 1.4 (SD = 1.8) years prior to AD treatment. Patients initially diagnosed with mild and moderate AD spent a median (95%CI) of 3.7 (2.8; 4.4) and 11.1 (6.1, ‘not reached’) years until progression to moderate and severe AD, respectively, according to the Mini-Mental State Examination (MMSE) scores. A mixed model developed for cognitive, functional, and neuropsychiatric scores, obtained from study patients at baseline and during follow-up period, showed progressive deterioration of AD patients over time. Conclusion: The study showed a deterioration of cognitive, functional, and neuropsychiatric functions during the follow-up period. Cognitive deterioration was slightly faster in patients with moderate AD compared to mild AD. The duration of moderate AD can be overestimated due to the use of retrospective data, lack of availability of MMSE scores in clinical charts and exclusion of patients at time of institutionalization.


2020 ◽  
pp. 1-14
Author(s):  
Jessica Mozersky ◽  
Sarah Hartz ◽  
Erin Linnenbringer ◽  
Lillie Levin ◽  
Marissa Streitz ◽  
...  

Background: Cognitively normal (CN) older adults participating in Alzheimer’s disease (AD) research increasingly ask for their research results—including genetic and neuroimaging findings—to understand their risk of developing AD dementia. AD research results are typically not returned for multiple reasons, including possible psychosocial harms of knowing one is at risk of a highly feared and untreatable disease. Objective: We developed materials that convey information about 5-year absolute risk of developing AD dementia based on research results. Methods: 20 CN older adults who received a research brain MRI result were interviewed regarding their wishes for research results to inform material development (Pilot 1). Following material development, 17 CN older adults evaluated the materials for clarity and acceptability (Pilot 2). All participants were community-dwelling older adults participating in longitudinal studies of aging at a single site. Results: Participants want information on their risk of developing AD dementia to better understand their own health, satisfy curiosity, inform family, and future planning. Some articulated concerns, but the majority wanted to know their risk despite the limitations of information. Participants found the educational materials and results report clear and acceptable, and the majority would want to know their research results after reviewing them. Conclusion: These materials will be used in a clinical study examining the psychosocial and cognitive effects of offering research results to a cohort of CN older adults. Future AD research may incorporate the return of complex risk information to CN older adults, and materials are needed to communicate this information.


2019 ◽  
Author(s):  
Rewadee Jenraumjit ◽  
Surarong Chinwong ◽  
Dujrudee Chinwong ◽  
Tipaporn Kanjanarach ◽  
Thanat Kshetradat ◽  
...  

Abstract Objective Age-associated decline in central cholinergic activity makes older adults susceptible to harmful effects of anticholinergics (ACs). Evidence exists of an association between effects of AC medications on cognition. This retrospective cohort study examines how ACs affect cognition among older adults with Alzheimer’s disease (AD) who received acetylcholine esterase inhibitors (AChEIs) over the course of 12 months. Results A total of 133 (80% women, mean age 78.38 years, SD 7.4) were recruited. No difference in sex, age and comorbid diseases was observed between participants who took ACs, Benzodiazepines (BZDs) and AChEIs. The most common prescribed ACs was quetiapine, being used for behavioral and psychological symptoms (BPSD). Multilevel analysis showed that the change of mental state examination scores were significantly predicted in the group using ACs (t (169), -2.52, p = .020) but not with the groups using BZD (t (162), 0.84, p = .440). Evidence showed that older adults with Alzheimer’s disease and exposed to ACs exhibited lower global cognitive scores than those without AC exposure. Using ACs could be a trade-off between controlling BPSD and aggravating cognitive impairment. Highlighting the awareness of the potential anticholinergic effect is important and may be the best policy.


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