Cause of death ranking changes of ADRD in China

In 2019, the top five causes of death were cerebrovascular diseases, ischaemic heart diseases, chronic obstructive pulmonary diseases, lung cancer and AD, respectively. In the past 30 years, the ranking of AD deaths in China rose from 10th in 1990 to 5th in 2019, even though the age-standardised death rate declined by 0.39% (figure 1).

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Figure 1

Change in the ranking of Alzheimer’s disease and related dementias deaths in China from 1990 to 2019. COPD, chronic obstructive pulmonary disease.

Disability-adjusted life years ranking changes of ADRD

The disease burden of ADRD in China from 1990 to 2019 rose from 27th to 15th, with a 5.7% increase of age-standardised DALY (figure 2).

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Figure 2

Change in the DALY ranking of Alzheimer’s disease and related dementias in China from 1990 to 2019. COPD, chronic obstructive pulmonary disease; DALY, disability-adjusted life year.

ADRD death comparison between the world and China

In 2019, deaths due to ADRD worldwide reached 1 623 276 (407 465–4 205 719); China contributed 320 715 (76 156–843 371) deaths or 19.8% of the world total (table 2). The age-standardised death rate for ADRD in the world reached 22.9/100 000 (5.8/100 000–59.2/100 000); China reached 23.3/100 000 (5.7/100 000–61.3/100 000), which was slightly higher than the world level.

ADRD prevalence worldwide compared with that in China

In 2019, there were 51 624 193 (44 276 969–59 021 502) individuals with ADRD in the world; in China the number of patients with ADRD was 13 143 950 (11 021 211–15 299 015), accounting for about 25.5% of the global population (table 1). The global age-standardised prevalence of ADRD was 682.5/100 000 (585.2/100 000–782.7/100 000); in China it was 788.3/100 000 (664.6/100 000–912.8/100 000), which was higher than the global level.

ADRD DALY worldwide compared with that in China

In 2019, the ADRD DALY worldwide reached 25 276 989 (11 204 523–54 558 243), of which 23% of the burden came from China (5 977 040 (2 678 980–13 100 564)). The global age-standardised DALY rate was 338.6/100 000 (151/100 000–731.3/100 000), while the age-standardised DALY rate in China was 368.5/100 000 (165.4/100 000–795.2/100 000) (table 6), which was slightly higher than the global level.

Deaths due to ADRD by gender

As shown in table 2, the 2019 female death rate was 30.8/100 000 (7.3/100 000–80.2/100 000), twice as high as the male death rate of 14.6/100 000 (3.4/100 000–42.0/100 000). After age standardisation, the female death rate (24.9/100 000) was still higher than the male death rate (20.3/100 000).

Deaths due to ADRD by age groups

Age group analysis of ADRD deaths and rates among the population over 40 years old in 2019 showed a rise with advancing age and reached the highest point in the 85 years and over age group. Deaths for men in the over 85 years age group totalled 32 145, and the death rate was 945.4/100 000; deaths for women in this age group totalled 107 958, and the death rate was 1385.0/100 000. In all age groups, the death rate due to ADRD was higher for women than that for men.

Deaths due to ADRD by provinces and municipalities

In 2019, provinces and municipalities with higher crude ADRD death rates were mainly concentrated in coastal cities, such as Shanghai Municipality (34.0/100 000), and other areas of China, such as Chongqing Municipality (32.1/100 000), Jiangsu Province (31.1/100 000) and Zhejiang Province (30.1/100 000). After age standardisation, the ADRD death rate order of rank for municipalities and provinces was: (1) Tianjin Municipality (27.3/100 000), (2) Hebei Province (26.5/100 000), (3) Chongqing Municipality (25.3/100 000), (4) Zhejiang Province (25.2/100 000) and (5) Sichuan Province (25.1/100 000). The ADRD death rates in Northeastern China and parts of Central China were relatively low (table 3).

Prevalence of ADRD by gender

As shown in table 1, in 2019 the number of individuals with ADRD in China reached 13 143 950 (11 021 211–15 299 015), of which the male prevalence was 669.3/100 000 (555.0/100 000–780.1/100 000) and the female prevalence was 1188.9/100 000 (1003.6/100 000–1379.0/100 000). The prevalence of female patients with ADRD was about 1.8 times that of male patients with ADRD. After age standardisation, the standardised prevalence rate of women (871.7/100 000) was still significantly higher than that of men (663.9/100 000).

Prevalence of ADRD by age groups

In 2019, ADRD numbers and prevalence rates for the male and female population aged over 40 years were on the rise and showed a rapid increase in people between 70 and 74 years of age. Men in the 80–84 years age group reached the highest number, with a total of 1 004 237 and a prevalence of 11 990.7/100 000. Women aged 85 years and over reached the highest number, with a total of 2 277 864 and a prevalence of 29 222.2/100 000. The prevalence rates of all age groups showed that rates for women were higher than those for men.

Prevalence of ADRD by provinces and municipalities

In 2019, the provinces and municipalities with the highest prevalence of ADRD were mainly concentrated in the Northeast, Eastern China and some central regions, including Jiangsu Province (1212.1/100 000), Shanghai Municipality (1137.6/100 000), Jilin Province (1081.4/100 000), Zhejiang Province (1078.6/100 000) and Liaoning Province (1077.5/100 000). After age standardisation, the areas with higher prevalence rates were found mainly concentrated in Northern China, Southern China and parts of Northeastern China. The top five ranking provinces and municipalities were Hebei Province (928.5/100 000), Henan Province (889.3/100 000), Jilin Province (882.4/100 000), Guangdong Province (845.5/100 000) and Zhejiang Province (815.6/100 000) (table 3).

YLL due to ADRD by gender

As shown in table 4, in 2019, YLL due to ADRD in China reached 4 113 696 (972 998–11 434 550), with the YLL of females significantly higher than that of males. The YLL rate for males was 212.4/100 000 (48.4/100 000–603.1/100 000) and for females was 369.0/100 000 (87.3/100 000–1018.6/100 000), which was about 1.7 times the rate of males. After age standardisation, the standardised YLL rate was the same for males and females (274.6/100 000).

YLL due to ADRD by age groups

In 2019, YLL due to ADRD and the proportion of individuals in the over 40 years age group increased for both men and women. There was a dramatic increase in individuals in the 75–79 years age group. Men aged 80–84 years had the highest YLL, with a total of 340 629 and a YLL rate of 4067.1/100 000. Women aged 85 years had the highest YLL, with a total of 825 079 and a YLL rate of 10 584.7/100 000.

YLL due to ADRD by provinces and municipalities

In 2019, provinces and municipalities with high ADRD, YLL rates were mainly concentrated in Eastern China and parts of Southwestern China, including Chongqing Municipality (410.9/100 000), Shanghai Municipality (390.0/100 000), Jiangsu Province (372.2/100 000), Zhejiang Province (357.1/100 000) and Sichuan Province (351.1/100 000). After age standardisation, the areas with higher YLL rates were mainly concentrated in Northern China and Western China. The top five ranking provinces and municipalities were Tianjin Municipality (297.7/100 000), Hebei Province (289.3/100 000), Chongqing Municipality (277.2/100 000), Sichuan Province (276.1/100 000) and Qinghai Province (275.3/100 000) (table 3).

YLD due to ADRD by gender

As shown in table 5, in 2019, YLD due to ADRD in China reached 1 863 344 (1 312 518–2 518 524), and the YLD for females was significantly higher than that for males. The YLD rate for males was 94.4/100 000 (66.1/100 000–127.9/100 000), and for females, it was 169.1/100 000 (118.7/100 000–228.1/100 000), which is about 1.8 times that of males. After age standardisation, the standardised YLD rate for females (125.2/100 000) remained higher than that of males (97.3/100 000) (table 5).

YLD due to ADRD by age groups

In 2019, ADRD YLD numbers for both men and women increased with ageing and were similar between the 80–84 years and over 85 years age groups. YLD rates showed a rapid increase in individuals in the 75–79 years age group. Men aged 80–84 years had the highest number with 111 206 and a YLD rate of 3270.7/100 000. Women aged over 85 years had the highest number with 352 324 and a YLD rate of 4519.9/100 000.

YLD due to ADRD by provinces and municipalities

In 2019, the provinces and municipalities with high ADRD YLD rates were mainly concentrated in Eastern China and parts of Southwestern China, including Chongqing Municipality (173.5/100 000), Jiangsu Province (173.0/100 000), Shanghai Municipality (163.1/100 000), Zhejiang Province (153.6/100 000 and Jilin Province (152.2/100 000). After age standardisation, the regions with higher YLD rates were mainly concentrated in Northern China, Southern China and parts of Northeastern China. The top five ranking provinces and municipalities were Hebei Province (133.9/100 000), Henan Province (128.7/100 000), Jilin Province (128.5/100 000), Guangdong Province (122.3/100 000) and Zhejiang Province (117.0/100 000) (table 3).

DALYs due to ADRD by gender

As shown in table 6, in 2019, DALY due to ADRD in China reached 5 977 040 (2 678 980–13 100 564), of which 31.2% was disability-related burden, and 68.8% was premature death-related burden. The DALY rate for females was significantly higher than that of males. The DALY rate for males was 306.8/100 000 (135.3/1 00 000–704.3/100 000); for females, it was 538.1/100 000 (246.7/100 000–1154.7/100 000), which is about 1.8 times higher than the rate for males. After age standardisation, the standardised DALY rate for females (399.9/100 000) remained higher than that for males (321.3/100 000) (table 6).

DALYs due to ADRD by age groups

In 2019, ADRD DALY numbers and rates for both men and women increased with ageing and showed a rapid increase in the 75–79 age group. Men aged 80–84 years had the highest number of DALY with 505 000 and a DALY rate of 6029.7/100 000. Women aged 85 years and above had the highest number of DALY with a total number of 1 177 403 and a DALY rate of 15 104.6/100 000.

DALYs due to ADRD by provinces and municipalities

In 2019, the provinces and municipalities with high ADRD DALY rates were mainly concentrated in parts of Southwestern China and Eastern China, including Chongqing Municipality (584.4/100 000), Shanghai Municipality (553.1/100 000), Jiangsu Province (545.1/100 000) and Zhejiang Province (510.7/100 000). After age standardisation, the regions with higher DALY rates were mainly concentrated in parts of Northern China, Southwestern China and Eastern China. The top five ranking provinces and municipalities were Hebei Province (423.2/100 000), Tianjin Municipality (414.5/100 000), Chongqing Municipality (391.8/100 000), Zhejiang Province (391.1/100 000) and Sichuan Province (390.2/100 000) (table 3).

Routine imaging technologies

To identify the degree of brain atrophy and possible causes of cognitive disorder, magnetic resonance imaging (MRI) and computed tomography (CT) are of the utmost importance in diagnosing AD. MRI is the first choice for its irreplaceably high resolution in neuroimaging, while CT serves as an alternative for patients with contraindications to MRI (eg, heart pacemaker). Routine sequences for MRI include T1-weighted imaging, T2-weighted imaging, fluid-attenuated inversion recovery and diffusion-weighted imaging.17 Although highly anticipated in cognition-related scientific research, other acquisition technologies, such as resting-state and task-state functional MRI, still have a long way to go before being widely used in clinical diagnosis.

Molecular imaging technology

The AD research framework (eg, amyloid-beta, tau, and neurodegeneration (ATN) system), established by the National Institute on Aging and Alzheimer’s Association (NIA-AA) in 2018, highlights the importance of positron emission tomography (PET) in the diagnosis of AD from the preclinical stage to the dementia stage.18 Depending on the substances targeted by radioactive tracer, AD-related PET examinations can be classified into three main kinds: Aβ-PET, tau-PET and fluorodeoxyglucose (FDG)-PET. However, the application of PET examination continues to be restricted by its relative expense and a lack of effective targeted therapies focusing on eliminating Aβ, tau or other pathological depositions.19 Whether it merits broad application in clinical work requires a comprehensive evaluation of its economic costs and health benefits.

Aβ-positron emission tomography

Increasing importance has been attached to Aβ-PET as it allows qualitative and semi-quantitative measurement of β-amyloid in the brain in vivo. The prevailing Aβ tracers include ¹¹C-Pittsburgh compound B (¹¹C PiB), ¹⁸F-florbetapir (namely ¹⁸F-AV-45, most commonly used in China), ¹⁸F-florbetaben and ¹⁸F-flutemetamol.20 It was reported that the sensitivity of Aβ-PET could reach 80%–100%, with a specificity of 66%–96%,21 leading to increased accuracy and confidence in the diagnosis. Meanwhile, the detection of preclinical AD raises the unresolved, inevitable ethical issue: whether and how to disclose the positive result of Aβ-PET to the examinees and their relatives.

Cognitive assessments

Cognitive screening/assessing scales commonly used in memory clinics include the Alzheimer’s Disease-8 (AD-8), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Addenbrooke’s Cognitive Examination-III (ACE-III). MMSE is the first choice for clinicians to screen patients with mild-to-moderate cognitive impairment, while the utility of AD-8, also useful but somewhat basic, is limited to primary screening. The prevailing Chinese version of the MMSE, translated and validated by Katzman et al,26 has been widely used for >30 years because of its satisfactory sensitivity and specificity in detecting dementia. Due to the latent ‘ceiling effect’ and ‘floor effect’, it is not suitable to use MMSE alone to detect cognitive impairment in MCI or early AD, especially for those individuals who are highly educated. Thus, further evaluation by the MoCA, ACE-III, or other more comprehensive scales is necessary.

The MoCA is highly sensitive in assessing patients in the early stages of dementia. The Chinese version of the MoCA varies with cultural and regional differences. Five mainstream versions are the Beijing, Changsha, Guangzhou, Hong Kong, and Taiwan versions. Additionally, because the language-related task in the MoCA is not suitable for patients with low education, a specially revised version, the MoCA basic, was drafted and validated by Chen et al and Huang et al.27 28 Other cognitive scales testing global cognition (eg, ACE-III) or specific domains (eg, Auditory-Verbal Learning Test) are also recommended if time allows or if carried out in a memory clinic setting. Considering the five cognitive domains—attention, memory, language, verbal fluency and visuospatial abilities—the ACE-III is highly accurate in identifying early AD and frontotemporal dementia. The widely used Chinese version was adapted by Fang et al 29 for the first time when the relevant cultural norms were also established.

Non-cognitive neuropsychological assessment

Apart from cognition, the evaluation of independent living skills and neuropsychiatric and behavioural symptoms plays an essential role in diagnosing and treating AD. For assessing these abilities, the activities of daily living (ADL) scale, the most widely used tool in clinical practice, is classified into two types—the basic ADL and the instrumental ADL (IADL), with the Barthel index being the most favoured. By grading abilities like toileting and dressing, it is apparent that the ADL can provide a reference for whether intensive care should be provided to the individual with dementia. In addition, brain atrophy is often accompanied by neuropsychiatric and behavioural abnormalities. The scales that evaluate these symptoms for differential diagnosis (eg, pseudodementia) and timely antipsychotic intervention are indispensable. For example, the Geriatric Depression Scale, the Neuropsychiatric Inventory (NPI), and the Hamilton Anxiety Scale are among the most commonly used scales for this purpose.

Electronic screening tools

Several digital cognitive tests have emerged as popular screening tools for AD, especially in numerous community hospitals within China. Compared with traditional methods, digital screening significantly reduces the information bias resulting from examination by different clinicians. However, electronic devices may cause some difficulties for those with a low education level or poor vision and could cause excessive stress to users. Some commonly used digital screening tools include simple cognitive scales like the AD-8, IADL, and others involving tracking of eye movements and language characteristics. For example, an automatic speech recognition software programme developed by Qiao et al 30 has been shown to effectively distinguish MCI/AD from healthy controls by analysing the language features (eg, percentage of silence duration) of participants (figure 3).

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Figure 3

Distinguishing normal controls (NC) from mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using a self-developed software programme for speech analysis.97

CSF biomarkers

Similar to the AD-related PET examination mentioned above, the widely accepted CSF biomarkers mainly target Aβ (Aβ42, Aβ40) and tau protein, both recommended in the NIA-AA diagnostic framework. Multiple studies31 32 have shown that the Aβ42/40 ratio in CSF performs better when diagnosing AD and predicting progression than using Aβ42 alone, with a sensitivity of 93.3% and a specificity of 100%. Nevertheless, due to variability in current detection methods and assay batches, a unified cut-off has yet to be established.

As a biomarker of AD, CSF tau has a lower diagnostic accuracy than Aβ measurements, partly because tau-mediated neuronal damage occurs later than Aβ accumulation.33 Increased tau protein in CSF is caused by degeneration of axon and neurofibrillary tangles. Specifically, the level of total-tau (t-tau) in CSF has been shown to increase significantly by nearly 300%, with a sensitivity of 80%–90% in AD diagnosis.34 This phenomenon, however, can also be found in dementia with Lewy bodies, stroke, traumatic brain injury and Creutzfeldt-Jakob disease, suggesting elevated t-tau can only marginally help to distinguish AD from other neuronal injuries. Also, it is essential to note that tau has a variety of types of post-translational modifications, mainly phosphorylation. In comparison with t-tau, elevated phosphorylated tau (p-tau) in CSF can better characterise the pathology of AD—the formation of neurofibrillary tangles—with relatively better sensitivity (81%) and specificity (47.5%).35 More than 30 phosphorylation sites of tau protein have been found, such as p-tau181 (commonly used), p-tau217 and p-tau231. Janelidze et al showed that p-tau217 could outperform p-tau181 in differentiating AD from other neurodegenerative diseases.36

To achieve satisfactory sensitivity and specificity in AD diagnosis, it is necessary to combine various Aβ and tau biomarkers in CSF, for example, Aβ42/40 and p-tau, or even p-tau/Aβ ratio.37 However, the main limitation of the utility of CSF biomarkers is that lumbar puncture, an invasive operation, cannot be used in almost any outpatient memory clinic in China.

Blood biomarkers

A set of blood tests, including examinations of complete blood count, thyroxine, antithyroid antibodies, antisyphilis antibodies, folic acid and vitamin B₁₂, are required for all patients with suspected AD to rule out other diseases associated with cognitive impairment. Remarkably, many new blood biomarkers are being developed and are expected to facilitate AD diagnosis or even replace CSF biomarkers in the future. Most of the blood biomarkers under development target either Aβ or tau protein.

Decreased total Aβ, Aβ42, and Aβ42/40 ratio and increased p-tau (eg, p-tau181, p-tau217) have been found in the plasma (or serum) of patients with AD as in CSF, making them potential biomarkers in diagnosis. Other promising blood biomarkers include neuro-exosomal synaptic proteins,38 neurofilament light chain39 and beta-secretase 1. It was reported that some blood biomarkers could detect AD much earlier than PET. However, it is worth noting the content of Aβ or other biomarkers in the blood is so small that testing for these measurements always comes with inevitably low sensitivity. Thus, an important area of research in this field is focused on developing better detection technologies for trace amounts of protein, for example, the optimised ELISA kit and immune-infrared sensor.40 No blood biomarker has been acknowledged by any canonical diagnostic guideline so far, suggesting there is a long way to go before its wide application.

Urine biomarkers

Previous literature suggested that urine AD7c-NTP has been demonstrated to be a sensitive and specific biomarker for diagnosing probable AD.41 42 Recently, a study by Zhang et al 42 showed that 68.8% of Aβ-positive subjects showed elevated urine AD7c-NTP levels, and AD7c-NTP level positively correlated with agitation score on the NPI. Additionally, according to the results of two Chinese pilot cohorts,43 44 both urinary monocyte chemoattractant protein-1 and dysregulated arginine metabolism are found to be potential biomarkers for diagnosing MCI/AD. However, there is also a long way to go before these can be applied in clinical work.

Anti-Aβ therapy

Anti-Aβ therapeutic strategies aim to either increase Aβ clearance, such as immunotherapy using monoclonal antibodies against Aβ, or decrease Aβ production, including β-secretase inhibitors and γ-secretase inhibitors. Immunotherapy is considered one of the most remarkable therapeutic approaches64 and may be the first method to modify this disease.61 Currently, three monoclonal antibodies targeting Aβ are in clinical trials in China—SHR-1707, lecanemab and gantenerumab. SHR-1707 (ClinicalTrials.gov Identifier: NCT04973189) was approved for phase I clinical trials in March 2021. Lecanemab and gantenerumab, which are in international, multicentre trials, are currently in phase III. In phase II clinical trial, lecanemab revealed therapeutic potential in CSF biomarker reduction, but it failed to reach the 12-month primary end point.65 A phase III randomised trial of gantenerumab was halted early because no differences were observed in the primary and secondary end points, although it reflected dose-dependent and APOE-ε4 genotype-dependent effects on biomarker end points in prodromal AD.66 A phase III clinical trial carried out to evaluate the efficacy and safety of subcutaneous injection of gantenerumab on early AD is in progress. β-Secretase is supposed to play a pivotal role in the process of amyloid-β peptides generation. However, the β-secretase inhibitor lanabecestat failed in two phase III studies (AMARANTH and DAYBREAK-ALZ) because it failed to slow memory decline in patients with early AD and mild AD dementia. Moreover, side effects in the lanabecestat group, such as psychiatric adverse events, weight loss and hair colour changes, were reported in a higher percentage than in the placebo group.67

Neuromodulation therapy

The number of registered clinical trials of neuromodulation therapy for AD has continuously increased in recent years. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are the two most widely investigated non-invasive brain stimulation (NIBS) interventions. Accumulating evidence suggests that NIBS may be an effective method for patients with AD. Studies have found that daily tDCS at home for 6 months can improve or stabilise cognitive performance in patients with AD,68 and rTMS combined with cognitive training intervention improves memory in patients with AD.69 70 Currently, an array of registered clinical trials of tDCS, transcranial alternating current stimulation and deep brain stimulation are under investigation for their potential clinical use. However, many variables in the clinical trials, such as study design, inclusion and exclusion criteria, sample size or funding source, may lead to inconsistent results.

Stem cell-based therapy

Numerous animal studies have shown that stem cell therapy can decrease or restrain neuronal death. Self-renewal, multipotent differentiation capabilities, low tumourigenicity and immunomodulatory properties make it a promising choice for neurodegenerative diseases.71 Mesenchymal stem cells and human neural stem cells are desirable candidates for AD treatment. One phase I/II clinical trial currently in progress is looking at exosomes derived from allogeneic adipose mesenchymal stem cells (allogeneic adipose MSC-Exos) in patients with mild-to-moderate dementia due to AD. Meanwhile, two clinical trials are underway evaluating the safety and efficacy of injection of human-derived neural stem cells via nasal drip in moderate-to-severe early-onset patients with AD. Nevertheless, many problems still need to be solved before going into clinical therapeutic application, such as eliminating the immune response and improving survival rate or obtaining large-scale production of effective and compatible cells.

Chinese medicine

Recent studies showed positive effects on AD from Chinese medicine, including traditional Chinese medicine and innovative Chinese compounds. An increasing number of Chinese traditional herbal medicines, including Liuweidihuang capsules, Taisi capsules, Bushenyijing granules, Yizhi decoction and Wujiayizhi granules, have been introduced to clinical trials in the past 2 years. Acupuncture, one of the most representative non-pharmaceutical treatments in traditional Chinese medicine, has attracted increasing attention recently due to its effectiveness and few side effects. A 28-week controlled study indicated that acupuncture could improve cognition and global clinical status in patients with mild-to-moderate AD.72 Two clinical studies, Sanlian Xingshen Yizhi Acupuncture therapy and acupuncture combined with donepezil, are ongoing to evaluate the efficiency and safety of acupuncture on AD.

Other therapies

In one recent clinical trial, folic acid combined with vitamin B₁₂ showed a positive therapeutic effect on cognition in patients with AD.73 Preclinical evidence suggested sulforaphane has a multifaceted neuroprotective effect on brain health. A randomised, double-blind, placebo-controlled study (NCT04213391) was carried out to study the efficacy and safety of sulforaphane in patients with prodromal to mild AD. In another clinical study, the antipsychotic amisulpride was used to relieve the neuropsychiatric symptoms of patients with AD. Also, music therapy combined with strong light therapy was found to improve sleep quality for those with sleep disorders.74 Non-pharmaceutical interventions, such as music therapy, cognitive interventions, aerobic exercise and diet therapy, have fewer side effects and may provide promising therapeutic options for patients with AD.

Although significant progress has been made in the past 2 years, many problems and limitations with clinical studies conducted in China continue to exist. Most trials have not been registered prior to implementation, and some have not been carried out in accordance with the standard statements of clinical trial reporting. More standardised top-level, large-sample size, multicentre studies are needed in the future.

In response to the appeal of ‘Healthy China Action (2019–2030)’,10 the General Office of the National Health Commission issued a document on how to explore more effective prevention and treatment service for patients with AD in August 2020. It aims to accelerate establishing a public service system with Chinese characteristics and explore an integrated intervention mode. In the future, the treatment of AD in China would include comprehensive management based on the patients’ life span cycle, including specific disease-modifying medications, treatment of comorbidities, early interventions for risk factors and changes in personal lifestyles.

Government support

As the rate of population ageing in China increases, the accompanying increased risk of cognitive impairment has led to an increased social risk. In the future, this social problem is likely to escalate. The government and society are paying increasing attention to cognitive impairment disorders such as AD. In the ‘Healthy China 2030’ plan,10 the Chinese government has proposed to ‘improve effective interventions for diseases such as AD’ and ‘the public’s awareness of the prevention and treatment of AD in pilot areas will increase to 80% by 2022’.10 It is necessary to establish and improve the Alzheimer’s prevention and treatment service network; moreover, the screening rate of cognitive function among the older adults in the community is expected to increase to 80%. Additionally, it is essential to ‘establish a multidisciplinary team providing diagnosis, treatment and nursing services for patients with MCI and dementia that includes general practitioners, volunteers, social workers, psychotherapists, and so on’. In addition, the National Health Commission of the People’s Republic of China is conducting a study on the ‘Guidelines for Home Care of Older Adults with Dementia’. To reduce the occurrence of disability and dementia in the older adults at its source, on 9 April 2021, the National Health Commission of the People’s Republic of China issued the ‘Notice on Pilot Programs for the Prevention and Intervention of Disability (Dementia) in Older Adults’,78 which aims to carry out pilot programmes in 13 provinces (cities, districts). Furthermore, they formulated the ‘Technical Plan for the Pilot Prevention and Intervention of Disability (Dementia) among Older Adults’.79 The Inner Mongolia Autonomous Region and Guangdong Province collaborated in this pilot project. Recently, intervention projects have been fully implemented in cities and districts of 15 intervention provinces.

Shanghai is a large city with the most rapidly ageing population in China and was one of the first cities to witness the increase in its ageing population. In 2017, 170 000 older adults with dementia lived in Shanghai, accounting for 6.7% of older adults with registered permanent residences in Shanghai.80 The Shanghai government’s strategies for dealing with dementia are relatively advanced compared with the rest of the country, and the following shows some of their pioneering work. In the ‘Healthy Shanghai 2030 Planning Outline’,81 Shanghai proposed to ‘promote healthy ageing, be demand-oriented, build a full-coverage and integrated older adult health service system, as well as improve the health management for older adults and implement interventions for common chronic diseases, degenerative diseases and mental health problems among elderly adults’. One of the main tasks of the ‘Shanghai Implementation Plan for Developing Elderly Care Services (2019–2022)’82 is improving healthcare services for older adults with cognitive impairment. In addition, Shanghai issued the ‘Notice on Strengthening Care Services for the Elderly with Cognitive Impairment in Older Adults Care Services’,83 proposing to ‘improve institutional care, community intervention and social education for older adults with cognitive impairment to create a social environment full of concern, care and love for older adults with cognitive impairment, improve the level of care services for older adults with cognitive impairment and promote the high-quality development of older adult healthcare services’. The notice also states that efforts will be made to create more beds for the administration of cognitive care. As of the end of 2020, the city has built 4999 beds to facilitate dementia care, and by 2022, there will be 8000 dementia care beds available in the city. The latest ‘Fourteenth Five-Year Plan for the Development of Civil Affairs in Shanghai’84 was released on 13 August 2021. It once again emphasised the critical position of management and care services for older adults with cognitive impairment. Moreover, it emphasised that during the ‘14th Five-Year Plan’ period, Shanghai will continue to carry out the prevention, early identification and interventions for common mental disorders seen in older adults, such as cognitive impairment and depression. Furthermore, Shanghai will continue to prioritise pilot projects aimed at older adults and promote cognitive impairment-friendly communities to achieve full coverage in its districts. The plan also mentioned promoting the construction of cognitive impairment care beds in pension institutions, reaching 15 000 beds by the end of the ‘14th Five-Year Plan’ period.

The national government provides medical, rehabilitation, entertainment, education, and other social assistance services to disabled and older adults with dementia with particular difficulties in rural areas. The National Working Committee on Aging and other functional departments have organised several special surveys on the development of rural older adults across the country to fully understand the basic conditions of the disabled and older adults with dementia in rural areas.

Long-term care insurance

In June 2016, the Ministry of Human Resources and Social Security of the People’s Republic of China issued the ‘Guiding Opinions on the Pilot Program of Long-term Care Insurance’85 and selected 15 cities to carry out this pilot project together. Moreover, they mentioned the exploration of establishing a social insurance system that raises funds through social mutual aid and assistance to provide service guarantees for basic living care and medical care for persons with long-term disability and dementia. There were two groups of national long-term care insurance pilot projects, and 49 cities have participated in the projects as of 2021. By the end of June 2021, the total number of participants in each pilot city for long-term care insurance reached 134 million, and the cumulative number of people receiving benefits reached 152 million.

Resource allocation for pension institutions

Pension institutions are essential providers of specialised cognitive impairment services. For example, some pension institutions have designated dementia care areas specifically designed to be friendly, safe environments that can better deliver daily services to patients.88 A survey in Beijing showed that the average occupancy rate of beds in the dementia care area in these institutions was 13.7% higher than ordinary beds. In recent years, Guangdong, Shanghai, Beijing and other cities have successively complied with the construction specifications, guidelines and service standards for dementia care areas; these standards are being used to guide the improvement of pension institutions and standardise related services, such as the ‘Work Plan for Dementia Care Bed Setting (Trial)‘89 and the ‘Guidelines for Dementia Care Bed Setting’90 issued in Shanghai in 2018.

There are three main types of existing pension institutions in rural areas, including social welfare institutions for older adults or retirement homes, apartments for older adults (nursing homes), and assisted living. They mainly accept older adults with no ability to work, no source of livelihood, and no one to support them financially. These older adults are guaranteed food, clothing, shelter, medical care and end-of-life/burial services, and are given various services such as daily life care and rehabilitation services. However, a serious shortage of assisted living centres in rural areas exists. Most small towns have only one nursing home that only provides water and electricity, cheap meals and simple living facilities. Also, cultural and entertainment facilities are lacking, along with little attention to the mental health of these older adults.91

Community-based and home-based resource allocation

With the further expansion of China’s elderly care service system, the importance of community-based and home-based care has gradually become more prominent. More than 90% of cognitive impairment patients in China currently choose home-based care, which is also the main future direction for dementia rehabilitation.

Different medical and elderly care institutions play various roles in preventing and treating disorders of cognitive impairment. Community health service centres are generally responsible for initial screening and intervention. In contrast, nursing homes, community day care centres and elderly care homes are responsible for the nursing care of patients. In addition, the community should be accountable for the health education of patients with cognitive impairment and their families, actively carrying out general public health intervention projects and activities that raise awareness about these issues. Finally, specialised geriatric nursing hospitals are responsible for treating patients with AD who are unable to care for themselves, are bedridden, have many complicating medical problems or require hospitalisation.

All provinces and cities have expanded their older adult services to include community and home-based care. For example, as of 2021, Jiangsu Province had built 18 200 home-based community senior service centres, 589 daycare centres and >7000 meal assistance points for older adults, with 2.6 million older people receiving specialised home-based services. At present, 77 subdistricts and towns in Shanghai have piloted the construction of the ‘Shanghai Dementia-Friendly Community’. Based on the characteristics of their respective communities and the needs of older individuals, ‘health education’ has been implemented to increase awareness of cognitive impairment among community residents. In addition, assessment of older adults in the community has been carried out to support early intervention, and training about non-drug-based interventions and guidance for family members is offered. For example, various methods of family support include psychological support, resiliency training and respite services. Finally, each subdistrict relies on community service centres for older adults and other facilities to establish a community support network for those with cognitive impairment.

Resource allocation for non-governmental organisations

Non-governmental organisations, including volunteer groups, public welfare organisations and other social members, play increasingly important roles in preventing and treating cognitive impairment disorders. They work with government agencies and communities to develop various activities, such as education and training for the general public.

For example, in 2013, the Changshou Road subdistrict in Shanghai organised public welfare organisations to open the city’s first memory school. To date, it has held >720 classes and has effectively served >14 400 people. In 2017, the Jian’ai Charity and Changshou Road subdistrict took the lead in launching the country’s first ‘Five-Year Plan’ for dementia-friendly community service in Shanghai, which has become an important project in the process of building a service system for the dementia-friendly community in Shanghai.

Service map for cognitive impairment

The online hospital is a new application combining the internet and medical field services. It is a healthcare service platform that uses the internet as a carrier which can optimise the procedures for medical treatment and make the experience of seeing a provider more convenient. From 2011 to March 2020, the State Council, the National Health Commission, the National Healthcare Security Administration and relevant local government departments issued a total of 110 internet-related policies; from these, the online hospital began to issue pilot policies in Guizhou and Yinchuan in 2015. In 2018, the General Office of the State Council issued the ‘Opinions on Promoting the Development of “Internet Plus Medical Health”’,93 which clarified the boundaries of internet medical services. Three documents including the ‘Administrative Measures for Internet Diagnosis and Treatment (for Trial Implementation)’,94 ‘Internet Hospital Management Measures (for Trial Implementation)’95 and ‘Management Standards for Telemedicine Services (for Trial Implementation)’96 formulated by the National Health Commission and the State Administration of Traditional Chinese Medicine, further clarify the online and offline business development of online hospitals. Online services include triage, guidance, consultation, referral, appointments, registration, telemedicine (including video consultation, telephone consultation, graphic consultation, electronic prescription, billing and report query), medication guidance, health consultations, posthospital follow-ups, chronic disease management and contracting with family doctors. In contrast, offline services include providing patients with places for video consultation, health consultation, medication sales, delivery relying on retail drug enterprises and various medical services carried out after establishing cooperative relations with offline medical institutions.

With the current care service needs for cognitive impairment, the vigorous development of online medical platforms establishes a whole process service system. It includes prevention, screening, diagnosis, treatment, rehabilitation, care and support for cognitive impairment. The help of online hospitals breaks through the previous geographical and time limitations of medical institutions and nursing facilities. It effectively makes online and offline connections while significantly improving service efficiency. Moreover, it can provide convenient, accessible, evidence-based and reasonable guidance for patients with cognitive impairment and their caregivers. This can relieve their stress, which supports the prevention and treatment of cognitive impairment and further improves existing service systems.

At the beginning of 2020, the Shanghai Municipal Center for Disease Control and Prevention and the new online hospital jointly developed and improved a service map for cognitive impairment, expanding the scope of institutions and visually displaying various service resources in conjunction with special research results. Its main advantages are as follows: first, this makes it easier for experts to understand the organisation’s classification, layout and bed distribution. It also ensures that citizens can inquire about the organisation’s classification and surrounding organisations and readily obtain its general information (name, address, telephone number, bed information and pricing). Second, although cognitive impairment cannot be cured, early screening, early diagnosis and early treatment are essential for effective prevention and delay of the disease progression. It was for this reason that the platform was established via online hospitals. Functional modules such as online outpatient services, follow-up, rehabilitation, education, training, nutrition consultation, psychological counselling and legal assistance were established to conduct preliminary screening and self-testing for high-risk groups. Community families and primary, secondary and tertiary hospitals were linked to achieve hierarchical diagnosis and treatment and integrate service resources such as older adult care, which makes full use of the advantages of fast and efficient online hospital interconnection. The entire process of education, screening, referral, diagnosis, treatment, rehabilitation, nursing, care and hospice care for cognitive impairment is implemented through a combination of prevention and treatment, full-time and specialised integration, medical and nursing care and traditional Chinese and Western medicine. Third, through online video courses, live broadcasts and course training, various resources can be integrated to improve the public’s awareness of cognitive impairment. For the specific difficulties of caregivers, there are currently no support services, such as psychological counselling and legal assistance. It is foreseeable that in this new era during which COVID-19 will likely continue to affect people’s lifestyles profoundly, this online and offline integration model will play a significant role in the provision of healthcare delivery.

An example of internet medicine: the Shanghai Brain Health Alliance

The Shanghai Brain Health Alliance was implemented by the Shanghai Medical Society General Medical Section in conjunction with the online hospital. This is in accordance with the spirit and requirements of WHO’s Global Action Plan for public health, which is entitled the ‘Global Action Plan on the Public Health Response to Dementia 2017‒2025’13 and the Shanghai Municipal Government’s ‘Healthy Shanghai 2030’.81 It was established by 141 relevant institutions in the city. The Shanghai Brain Health Alliance is responsible for three main tasks. The first is to improve the clinical diagnosis and treatment of cognitive impairment in Shanghai. It aims to cooperate with Shanghai’s professional medical institutions to form a network that strives towards the prevention, screening, diagnosis, treatment, rehabilitation, standardisation of in-hospital treatment and out-of-hospital long-term management of patients with cognitive impairment. Furthermore, it aims to build a complete internal and external prevention management system, first prioritising primary diagnosis, followed by referral, acute and chronic treatment, and finally integration within the medical system to achieve ‘early prevention, early diagnosis and early treatment’. This will increase the detection and effective treatment rate of disorders and improve the city’s level of standardised prevention and treatment as a whole.

The second task is to improve the level of care for patients with cognitive impairment in the city, thus improving the collaboration and integration of healthcare and civil older adult care institutions. At the individual level, caregivers are more likely to obtain professional help, education and training to improve their care ability. At the institutional level, it will be easier to get professional medical support, enhance the quantity and quality of care institutions and improve the service level of the whole industry through the establishment of the alliance.

The third task is to enhance efficiency. An online and offline integrated prevention and care system has been built based on the online hospital platform. This overcomes obstacles posed by geography and time. For example, an online cognitive map 2.0 was launched to establish an online hospital specialised disease platform to display the city’s medical and care institutions (including parts of the Yangtze River Delta) to fully implement hierarchical diagnosis, treatment, drug distribution, evidence-based training, older adult care, rehabilitation, psychological counselling and legal assistance for the convenience of residents. Through the internet media matrix of communication and operation, promotion is used to improve the societal awareness of the disease and the concept of ‘health for all’.