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To investigate the extent to which frailty is associated with infection-related hospitalizations in older men and women, and to explore whether, among women, previous exposure to endogenous estrogens in terms of age at menopause and number of pregnancies modify such a relationship.The sample comprised 2784 participants in the Progetto Veneto Anziani aged ≥65 years. At baseline and after 4.4 years, frailty was identified according to the presence of three or more of the following: weakness, exhaustion, weight loss, low physical activity, and low walking speed. A passive follow-up on infection-related hospitalizations and mortality was performed for 10 years of observation through linkage with regional registers.The association between frailty and infection-related hospitalizations was assessed through mixed-effects Cox regressions.Frailty was significantly associated with a 78 % higher risk of infection-related hospitalization, with stronger results in men (hazard ratio = 2.32, 95 % confidence interval 1.63-3.30) than in women (hazard ratio = 1.54, 95 % confidence interval 1.18-2.02). Focusing on women, we found a possible modifying effect for the number of pregnancies but not menopausal age. Women who had experienced one or no pregnancy demonstrated a higher hazard of infection-related hospitalization as a function of frailty (hazard ratio = 3.00, 95 % confidence interval 1.58-5.71) than women who had experienced two or more pregnancies (hazard ratio = 1.68, 95 % confidence interval 1.18-2.39).Frailty in older age increases the risk of infection-related hospitalizations, especially in men. The "immunologic advantage" of the female sex in younger age seems to persist also after menopause as a function of the number of pregnancies a woman has experienced.

Cognitive Reserve (CR) plays a protective role in neurological and acute/chronic diseases. Its effect on mood, however, is still unclear, although it may be relevant in a hospital setting. We aimed to explore the relationship between CR and depressive mood in older inpatients, evaluating possible gender- and age-related differences. This study involved 86 inpatients aged ≥65 years with an MMSE ≥15. Participants underwent a multidimensional evaluation that included the assessment of CR with the Cognitive Reserve Index questionnaire, divided into three sections (Education, Working Activity, and Leisure Time). Depressive mood was assessed with the 15-item Geriatric Depression Scale (GDS). The relationship between CR and GDS was evaluated by multivariable linear regressions. Significant inverse associations between CR and GDS scores emerged in the total sample (β = -0.03 [SD = 0.02], p = .047), especially in men (β = -0.05 [SD = 0.02], p = .005) and in individuals aged85 years (β = -0.07 [SD = 0.03], p = .01). Among the single CRI sections, CRI-Leisure Time was significantly associated with GDS in the total sample, in men, and participants85 years. CR seems to be inversely associated with depressive mood in older inpatients. This relationship is particularly marked for CR related to Leisure Time, which may be modifiable even in older age through social support and interaction.

Background: Communicating bad news is of great interest in the geriatric field, but few works have considered the physician’s point of view in this regard. Objectives: The aim of this study was to explore possible differences related to physicians’ gender and work experience in how a terminal diagnosis is disclosed to older patients. Methods: Study participants were 420 Italian physicians (277 M, 143 F) working in clinical medicine (58.2%), surgery (33.3%), or other medical departments (8.5%). They completed an anonymous multiple-choice questionnaire that investigated various issues associated with communicating bad news to terminally ill older patients. Results: Men had more work experience than women (55.6% vs. 44.8% had worked for ≥23 years) and were more likely to work in surgery departments, while more women worked in clinical medicine. Most physicians declared that terminally ill older patients, if mentally competent, should always (14.4%) or generally (64.3%) be directly and openly informed of their condition. With no difference in gender, length of work experience, or specialty area, 36.9% of physicians thought that this was a human right and 18% that it would improve the patient’s quality of life. Where older patients were alone, male physicians were more likely than female (30.2% vs. 8.9%) to always communicate bad news directly to them. More than 70% of physicians, especially those with longer work experience, declared that they always or often took enough time to inform the patient. Female physicians and those working in clinical medicine were more likely to need psychological help when deciding to break bad news, but only a smaller proportion declared to have received it. Conclusions: Gender and work experience may influence how physicians communicate with patients and how often they seek psychological support.

Depression is one of the most common mood disorders in the late-life population and is associated with poor quality of life and increased morbidity, disability and mortality. Nevertheless, in older adults, it often remains undetected and untreated. This narrative review aims at giving an overview on the main definitions, clinical manifestations, risk and protective factors for depression in the elderly, and at discussing the main reasons for its under/misdiagnosis, such as cognitive decline and their overlapping symptomatology. A practical approach for the global and multidisciplinary care of the older adult with depression, derived from cross-checking evidence emerging from the literature with everyday clinical experience, is thus provided, as a short and flexible "pocket" guide to orient clinicians in recognizing, diagnosing and treating depression in the elderly.

Sociodemographic factors, such as education and occupation, may influence the individual's cognitive reserve. We explored the extent to which the type and complexity of previous work activities influence cognitive performance (evaluated with Mini-Mental State Examination, MMSE, and the Animal Naming Test, ANT) in 799 older people with or without brain damage. The presence of cortical/subcortical ischemic brain lesions and right/left hippocampal atrophy was derived from magnetic resonance imaging. We found that individuals who had done intellectual work had better MMSE and ANT scores than their counterparts in the presence of brain lesions or hippocampal atrophy. Among the manual workers there were significant differences between the MMSE scores of individuals with and without brain damage (mean MMSE difference (2.09 [SD: 0.68], p=0.01), but not among the intellectuals (0.19 [SD: 0.29], p=0.36) nor the service providers (1.67 [SD: 0.55], p=0.21). Occupations involving more complex dealings with people were associated with better MMSE scores in the presence of brain lesions [β=-0.41, 95%CI: -0.72,-0.09] and hippocampal atrophy [β=-0.29, 95%CI:-0.58,-0.001]. These results indicate that in more cognitively stimulating work with greater social interaction may help older individuals preserve cognitive functions, even in the presence of brain damage.

IntroductionCardiovascular benefits deriving from physical activity are well known, but it is unclear whether physical activity trajectories in late life are associated with different risks of cardiovascular diseases.MethodsProgetto Veneto Anziani (Pro.V.A.) is a cohort study of 3099 Italians aged ≥65 years with baseline assessment in 1995–1997 and follow-up visits at 4 and 7 years. Surveillance was extended to 2018 by linkage with hospital and mortality records. Prevalent and incident cardiovascular diseases (coronary heart disease, heart failure and stroke) were identified through clinical examination, questionnaire, or hospital records. Moderate to vigorous physical activity was considered as a time-varying variable. Physical activity trajectories were categorised as: stable-low, high-decreasing, low-increasing and stable-high. Exposure was also assessed at 70, 75, 80 and 85 years.ResultsOverall, physical activity was associated with lower rates of incident cardiovascular diseases. A significant risk reduction was present among men and was stronger earlier in late life (70–75 years). Trajectories of stable-high physical activity were associated with a significantly lower risk of cardiovascular outcomes among men (HR 0.48, 95% CI 0.27 to 0.86) compared with those with stable-low trajectories (p for trend 0.002). No significant association was found with stroke. The greatest cardiovascular risk reduction was observed for >20 min/day of physical activity, and was more marked at 70 years.ConclusionIncreasingly active trajectories of physical activity were associated with lower rates of cardiovascular diseases and overall mortality. Promoting at least 20 min/day of physical activity early in late life seems to provide the greatest cardiovascular benefits.

Approximately 50% of colorectal cancers occur in older patients. International societies recommend geriatric tools to optimise treatment of older patients. Comprehensive Geriatric Assessment (CGA) is a multidimensional assessment used to classify patients as fit, vulnerable, or frail. The CGA-based oncological multidimensional prognostic index (onco-MPI) also classifies patients as high-, intermediate-, or low-risk based on tumour characteristics. We investigated the role of CGA and onco-MPI in older patients with metastatic colorectal cancer (mCRC) in a real-world setting.Data for consecutive mCRC patients aged ≥70 years were retrieved from a prospectively maintained database from 2010 to 2020. We analyzed patients' and tumours' characteristics, and the CGA domains. Onco-MPI was calculated by a validated algorithm derived from CGA domains. Pearson's test was used to verify whether onco-MPI scores and chemotherapy administration were correlated.The study included 488 mCRC patients with a mean age of 76.1 years. According to CGA, 52% of patients were fit, 28% vulnerable, and 20% frail. According to onco-MPI, 9% were low, 54% intermediate, and 37% high-risk. The median OS was 22.7 months. The following factors improved OS: 0-1 ECOG PS, low onco-MPI, fit based on CGA, chemotherapy administration, and doublet regimen. Chemotherapy administration significantly correlated with onco-MPI scores, leading to a survival gain regardless of the risk subgroups. First-line regimen had no impact on survival across the CGA and onco-MPI categories.CGA and onco-MPI scores confirmed their prognostic impact in older mCRC patients and may aid in decision-making and subgroup stratification in dedicated trials.

Background While it is well established that frail older people have a higher risk of negative health outcomes, the prevalence of frailty and its associated factors in Italian older institutionalized population has never been investigated. Aims The aims of this study were to assess the prevalence of frailty and to identify its associated factors in an Italian residential care home population. Methods An observational cross-sectional study was designed to evaluate older people aged 70 or over of an Italian residential care home. A multidimensional assessment examining functional, geriatric, ophthalmic, and audiological domains was carried out to identify factors associated with frailty. Physical frailty was evaluated using Fried's criteria. Results Data analysis uncovered a 51.1% prevalence of pre-frailty and a 40.4% prevalence of frailty in the 94 eligible participants (64 females) whose data were complete. The multivariable analysis showed that a low education level (OR = 5.12, 95% CI 1.22-21.49), a low physical quality of life score (OR = 13.25, 95% CI 3.51-50.08), a low mental quality of life score (OR = 9.22, 95% CI 2.38-35.69), visual impairment (OR = 7.65, 95% CI 1.77-33.14), and hearing impairment (OR = 4.62, 95% CI 1.03-20.66) were independently associated with frailty. Conclusions Frailty was found to be highly prevalent in the residential care home studied. Since frailty is a reversible condition, identifying the modifiable factors associated to it should be viewed as an important step in planning and implementing targeted, early prevention strategies.

This prospective study evaluated cognitive and physical trajectories of nursing home (NH) residents after fall occurrence and their predictors. In 167 residents aged ≥60, we considered the closest pre-fall assessment and up to the first three post-fall assessments of cognitive and physical functions performed through Mini-Mental State Examination (MMSE) and Tinetti tests. Mixture models identified three post-fall cognitive and physical trajectories: stability, slow decline, and rapid decline. At logistic regression, older age, fewer informal visits, and falls within one month from institutionalization increased the probability of experiencing a decline in MMSE and Tinetti scores. Worse pre-fall cognitive function increased the likelihood of cognitive and physical decline, while worse pre-fall Tinetti score negatively impacted only physical decline. In conclusion, the impact of falls on the cognitive and physical health of NH residents may be modulated by their pre-fall cognitive function and some modifiable factors, such as social interactions and physical function.

Background and aims The most recent guidelines suggest treating patients whose FRAX 10-year fracture risk scores are ≥ 20%. However, this method of evaluation does not take into account parameters that are nonetheless relevant to the therapeutic choice. Our aim was to compare the therapeutic choices for treatment based on a wider assessment (real-world practice) with those based on FRAX scores, taking 20% as the cut-off score. Methods We obtained the medical history, bone mineral density (BMD) values, and the presence of major fragility fractures in a sample of 856 postmenopausal women. The 10-year FRAX risk of major osteoporotic fracture was calculated, and patients were grouped into risk classes (“FRAX Results 83% of high-risk patients and 57% of low-risk patients were treated. The therapeutic decision was based mainly on densitometric values and the presence of vertebral fractures. At the 2.5 year follow-up, lumbar spine and femur BMD had decreased in the untreated group; 9.9% of the treated patients developed new vertebral fragility fractures, compared with 5.3% of the untreated patients. Discussion and conclusions Our wider assessment designated as at high fracture risk a group of patients who had not been identified by the FRAX assessment. FRAX could underestimate the risk of fracture in older people, for which the therapeutic choice should consider a broader approach, also based on individual patient’s needs.

Introduction Evidence regarding safety and efficacy of oral anticoagulants for the treatment of atrial fibrillation (AFib) in older adults has been assessed regarding the age appropriateness of oral anticoagulants (OAC) according to the FORTA (Fit fOR The Aged) classification (OAC-FORTA). Three years after its first version (OAC-FORTA 2016), an update was initiated to create OAC-FORTA 2019. Methods A structured review of randomized controlled clinical trials and summaries of individual product characteristics was performed to detect newly emerged evidence on oral anticoagulants in older patients with AFib. This review was used by an interdisciplinary panel of European experts (N = 10) in a Delphi process to label OACs according to FORTA. Results A total of 202 records were identified and 11 studies finally included. We found four new trials providing relevant data on efficacy and safety of warfarin, apixaban, dabigatran or rivaroxaban in older patients with AFib. In the majority of studies comparing the non-vitamin-K oral anticoagulants (NOACs) with warfarin, NOACs were superior to warfarin regarding at least one relevant clinical endpoint. The mean consensus coefficient significantly increased from 0.867 (OAC-FORTA 2016) to 0.931 (p 0.8). Warfarin, dabigatran, edoxaban and rivaroxaban were assigned to the FORTA B label, acenocoumarol, fluindione and phenprocoumon were labeled FORTA C and only apixaban was rated as FORTA A. Conclusion OAC-FORTA 2019 confirms that AFib can be successfully treated with positively labeled antithrombotics at advanced age. Electronic supplementary material The online version of this article (10.1007/s40266-020-00771-0) contains supplementary material, which is available to authorized users.

Non-motor symptoms (NMSs) are common in Parkinson's disease (PD) and can precede, sometimes for several years. NMSs include, other than gastrointestinal symptoms like constipation and dysphagia, also hyposmia, weight loss and osteosarcopenia. These three NMSs seem to be inter-related and affect patients' health and quality of life. Unfortunately, patients with these symptoms usually are not initially seen by a neurologist, and by the time they are consulted, nearly ~ 80% of the dopaminergic neurons in the substantia nigra have died. To date, no guidelines exist for screening, assessment and management of NMSs in general. A better understanding of these specific NMSs, likely in the context of others, will make it possible to approach and optimise the treatment of the motor symptoms thereby enhancing the welfare of PD patients. Identifying the NMSs could be very helpful, and among them, hyposmia, weight loss and osteosarcopenia may play an important role in solving the limitations in the diagnosis of PD. A strict collaboration between general practitioners, clinicians, geriatricians and neurologists can be one approach towards the diagnosis of pre-PD. Waiting until the motor symptoms develop and the patient is finally visited by the neurologist could be too late, considering the catastrophic prognosis of the disease.

Polypharmacy has been associated with worse cognitive performance, but its impact on mild cognitive impairment (MCI) progression to dementia has not been explored. The aims of the study were to investigate the association between multidrug regimens and MCI progression, and the possible mediation of drug–drug interactions and drugs’ anticholinergic effect in such association. This work included 342 older adults with MCI, who were involved in an Italian multicenter population-based cohort study. Information on drugs taken was derived from general practitioners’ records and data on drug–drug interactions and anticholinergic burden [evaluated through the Anticholinergic Cognitive Burden and the Anticholinergic Risk Scale (ARS)] were extracted. Multinomial logistic regressions assessed the associations between mild polypharmacy (≥ 3 drugs/day), drug–drug interactions, and anticholinergic burden with MCI changes after 1-year follow-up. Mediation analysis evaluated potential mediators of that relationship. Approximately, 50% of participants took ≥ 3 drugs/day. During the follow-up, 4.1% of MCI patients progressed to dementia. The odds of developing dementia was sixfold higher in those who took ≥ 3drugs/day (OR = 6.04, 95% CI 1.19–30.74), eightfold higher in those with ≥ 1 drug–drug interaction/s (OR = 8.45, 95% CI 1.70–41.91), and fivefold higher in those with ARS ≥ 1 (OR = 5.10, 95% CI 1.04–24.93). Drug–drug interactions mediated 70.4% of the association between medication number and MCI progression to dementia (p = 0.07). Our study suggests that even mild polypharmacy may increase the risk of MCI progression to dementia, probably due to the presence of drug–drug interactions, which often occur in multidrug regimens. Older people require careful management of pharmacological treatments, with special attention to drug–drug interactions and drug-related anticholinergic effects.

Background The effect of dehydroepiandrosterone sulfate (DHEA-S) on fall risk in older age is still unclear, as is the effect of sex on any relationship between the two. Our aim was to evaluate the association between DHEA-S and the risk of falls and risk of recurrent falls in community-dwelling older men and women. Methods We included 1949 (781 M, 1168 F) older adults enrolled in the Progetto Veneto Anziani study. Baseline serum DHEA-S levels were analyzed by immunoassay. The number of falls reported in the year preceding the 4.4-year follow-up assessment was collected. The association between DHEA-S and falls was analyzed by multinomial logistic regression, adjusting for potential confounders and considering death as alternative outcome. Results After the follow-up, 548 (36.8%) individuals reported at least one fall in the previous year, and 214 (14.4%) reported ≥2 falls (recurrent falls). Each 1-standard deviation (SD) increase in log-transformed DHEA-S level reduced the odds of experiencing at least one fall by 9% (95%CI:0.88-0.95), and the risk of recurrent falls by 16% (95%CI:0.79-0.89). The highest DHEA-S tertile was 27% (95%CI:0.65-0.83) less likely to experience recurrent falls than the lowest tertile. The analyses, stratified by sex, suggested a strong association between DHEA-S and the fall risk for women (OR = 0.91; 95%CI:0.87-0.95 for at least one fall; OR = 0.83, 95%CI:0.78-0.89 for recurrent falls per each 1-SD increase in log-transformed DHEA-S); non-significant results were observed among men. Conclusions Higher levels of DHEA-S are associated with a lower risk of falls and recurrent falls in older people, especially women.

Aging is associated with low-grade chronic inflammation contributing to a decline in lung performance. The Dietary Inflammatory Index (DII) has been introduced to evaluate the inflammatory potential of different diets, which may further affect individuals' respiratory function. This study investigates the association between DII and lung performance in older adults.This cross-sectional study included 155 adults aged ≥65 y recruited at public gyms in Padua, Italy. Participants were assessed on medical history, biochemical parameters, body composition (through dual energy x-ray absorptiometry), anthropometry, and lung function (by spirometry). Based on individuals' dietary habits, we computed their DII and categorized participants in the lower DII (comprising those in the lowest DII tertile) or the higher DII (comprising those in the highest DII tertiles) groups. The association of DII with forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) was tested through multivariable linear regression analyses in the total sample and stratified by body mass index (25 kg/mThe mean age of the sample was 71.2 y and 80% were women. Individuals in the higher DII group had FEV1 and FVC values reduced by 0.15 L (95% CI, -0.29 to -0.01 L) and 0.25 L (95% CI, -0.43 to -0.07 L), respectively, as compared with those in the lower DII group. Results seemed to be more marked among participants with excess weight conditions.Pro-inflammatory diets may affect lung function in fit older people, and this effect may be exacerbated in overweight or obese individuals.

Background Surgical aortic valve replacement (SAVR) is still the gold standard for treating aortic valve stenosis (AVS). Its effectiveness has been extensively examined in terms of perioperative mortality, but its impact on overall health has received much less attention. Aims To assess the physical performance, cognitive status, and health-related quality of life of elderly patients undergoing SAVR, in the short, medium and long term. Methods This single-center prospective study enrolled patients aged > 70 years who underwent isolated SAVR for severe AVS. Data were collected on each participant’s clinical status, physical performance, cognitive status, mood, and health-related quality of life. This multidimensional geriatric assessment was performed before surgery (T0), and again at 45 days (T1), 3 months (T2), 6 months (T3), and 12 months (T4) post-surgery. Baseline (T0) and follow-up (T2-T4) data were compared separately for patients grouped by gender using paired t-tests. Results Data from a total of 35 patients were analyzed. Compared with the baseline (T0), nutritional status worsened at T1, then gradually improved through to T4. Physical performance, mood, and health-related quality of life improved significantly after surgery. Cognitive function showed no change through to T3, but then deteriorated at T4. Conclusions Our results show that SAVR in patients over 70 years of age has a positive impact on nutrition, mood, and health-related quality of life. Cognitive function was not negatively affected in the short and medium term, although it deteriorated in the long term. SAVR also had a positive impact on the physical performance of our sample.

Background & aims Vitamin D and parathormone (PTH) have been associated with cardiovascular outcomes, but their impact on atrial fibrillation (AF) onset is still unclear. We explored the influence of serum 25-hydroxyvitamin D (25[OH]D) and PTH on AF risk in older adults. Methods and results Data come from 2418 participants enrolled in the Progetto Veneto Anziani study. Serum 25(OH)D and intact PTH were measured using radioimmunoassay and two-site immunoassay, respectively. The associations between 25(OH)D, PTH and adjudicated AF cases over 4-years were explored by Cox regression. Over the follow-up, 134 incident cases of AF were assessed. The incidence rate of the sample was 13.5 (95%CI 11.4–15.9) per 1000 person-years, and was higher among those with high PTH levels (high: 16.4 [95%CI 11.3–24.0] per 1000 person-years), especially when associated to low 25(OH)D (20.3 [95%CI 12.9–32.3] per 1000 person-years). At Cox regression, only high PTH was significantly associated to an increased risk of AF (HR = 1.90, 95%CI 1.27–2.84). A marginal significant interaction (p = 0.06) was found between 25[OH]D and PTH concentrations in influencing AF risk. When exploring the risk of AF for combined categories of 25(OH)D and PTH, we found that those with high PTH and low 25(OH)D levels had an AF risk twice as high as that of people with normal values (HR = 2.09, 95%CI 1.28–3.42). Conclusion The risk of AF may be increased by high PTH levels, especially when associated with 25(OH)D deficiency. The identification and treatment of high PTH or vitamin D deficiency may thus contribute to lower the risk of AF.

Background and aims COPD is a common chronic condition in older age that impacts on daily activities and quality of life. Previous studies suggest that magnesium deficit in COPD patients affects bronco-obstruction, inflammation, and physical performance. We investigated whether oral magnesium supplementation in stable-phase COPD patients improves lung function, physical performance, and quality of life. Methods We conducted a double-blind randomized-controlled clinical study with 49 participants divided into two groups: one given 300 mg/day of magnesium citrate (n = 25) and the other one sachet/day of a placebo (n = 24). The following parameters were assessed at baseline and after 3 and 6 months: lung function (spirometry), physical performance (handgrip strength, lower limb strength, six-minute walk test), inflammation (e.g., C-reactive protein, CRP), disease-related symptoms, and quality of life (St George’s Respiratory Questionnaire, EuroQoL-5D, the Modified British Medical Research Council Questionnaire). Results Linear mixed models revealed significantly lower CRP values in the intervention group than in the placebo group at the 6 month follow-up (β = − 3.2, 95% CI − 6.0, − 0.4, p = 0.03). Moreover, the maximum work for flexion tended to increase in both groups between the 3 and the 6 month assessments, especially in the placebo group. No significant differences within and between groups over the study period were observed for the other parameters tested. Conclusions Although the established minimum sample size was not reached, our results suggests that oral magnesium supplementation may have a potential anti-inflammatory role. On the other hand, it does not seem to substantially influence lung function, physical performance, and quality of life in COPD patients. Trial registration The study is registered in clinicaltrial.gov (Trial Registration: NCT02680769, 13 June 2016, retrospectively registered).

The role of the cerebellum in neurodegenerative disorders that target cognitive functions has been a subject of increasing interest over the past years. However, a review focused on making clinicians more aware of the role of the cerebellum in dementia is still missing. This narrative review explores the possible factors explaining the involvement of the cerebellum in different kinds of dementia by providing more insights on how this structure can be relevant in clinical practice. It emerged that, despite overlapping in specific areas, structural cerebellar alterations in dementia show a certain degree of disease-specificity. Furthermore, the relevance of cerebellar changes in dementia is corroborated by correlations observed between their topography and cognitive symptomatology, as well as by its previously ignored involvement of the cerebellum in early stages of dementia. Despite needing further investigations, these findings could become a useful diagnostic aid for clinicians that should not be overlooked, in particular for those individuals who do not show distinct and manifest brain or neuropsychological alterations, but that still make clinicians suspect the presence of a neurocognitive disease.

Backgrounds Acetylcholinesterase inhibitors (AChEI) and cognitive stimulation (CS) are the standard pharmacological and non-pharmacological treatments for Alzheimer’s disease (AD). Aims The aim of this study was to investigate the effects of these treatments, alone or combined, on the neuropsychological profiles of patients with AD. Methods Forty participants were assigned to three groups receiving either only AChEI (n = 14), AChEI + CS (n = 15), or only CS (n = 11). Cognition was evaluated at baseline and after three months. Linear mixed-effects models were used to investigate differences among the treatments in terms of changes in the patients’ neuropsychological profiles. Results Results, although preliminary because of the small sample size, suggest that a general improvement was found in patients who received AChEI + CS and those who received only CS compared with those who received only AChEI. Interestingly, individuals who received only CS showed a significant improvement in immediate memory recall than those who received only AChEI. Furthermore, the group receiving AChEI + CS showed an improvement in delayed recall than the other two groups. Discussion The combination of AChEI and CS seems to have the greatest benefit for patients with mild AD. More interestingly, CS alone is more effective than AChEI alone, even in improving memory, considered to be the “lost” cognitive domain in AD.