Table 1.
Anxiety as a risk factor of Alzheimer’s disease in clinical trials.
| Year/Study design/Group | Mean age (SD) |
Country/Source of data/Study setting | Diagnostic criteria: Anxiety/AD | Main findings | Conclusions | Ref. |
|---|---|---|---|---|---|---|
| 1999/None/Community-dwelling AD patients (n=523) | \ | USA/University of Washington and Group Health Cooperative of Puget Sound/Clinic | DSM-IV/CT | Anxiety symptoms were common, occurring in 70% of subjects. | Anxiety symptoms were common and significantly related to ADL and additional neuropsychiatric problems in this sample. | [149] |
| 2003/Cross-sectional study/Probable AD (n=115), VaD (n=43), FTD (n=33), Controls(n=40) | 77.2(7.6); 75.1(9.8); 65.8(8.5); 73.6(6.1) | USA/UCLA Alzheimer’s Disease Center database/Clinic | NPI/NINCDS-ADRDA | In AD, anxiety was more prevalent among patients with a younger age at onset (under age 65). | In AD, anxiety is common in those with more severe cognitive deterioration and an earlier age at onset. | [150] |
| 2010/None/a-MCI (n=19), Ade (n=15), Adm (n=12), HS (n=23) | 73.3(6.9), 75.5(7.0), 70.0(8.2), 63.9(9.5) | Italy/Pecialist dementia clinic of Santa Lucia Foundation/Clinic | NPI-12, VBM/MRI | Anxiety was present in both a-MCI and AD. | Anxiety is present since the earliest AD stages. | [151] |
| 2013/Prospective pilot study/Early stage of AD patients (n=54), Healthy controls (n= 64) | 76.9(8.5); 69.3(8.7) | Switzerland/Memory Clinic of the Old Age Psychiatry Service of the Lausanne University /Clinic | NPI-Q/NINCDS-ADRDA | Behavioral and psychological symptoms, in particular apathy, anxiety, are frequent occurrences in early-stage AD. | Premorbid personality was not associated with BPS in early stage of AD, although complex and non-linear relationships between the two are not excluded. | [152] |
| 2014/None/EOAD patients (n=23), LOAD patients (n=22) | 57.68(4.19); 80.32(5.89) | USA/Departments of Neurology and Geriatric Psychiatry at the Veterans Affairs Greater Los Angeles Healthcare Center /Clinic | NPI/- | EOAD patients had significantly more anxiety symptoms than LOAD patients. | Among LOAD patients, anxiety was associated with psychotic and activating psychiatric symptoms. | [153] |
| 2015/Prospective cohort study/Healthy, older adults (n=333) | 70.0(6.8) | Australia/Australian Imaging, Biomarkers, and Lifestyle Study/Clinic | HADS/PET, APOE genotyping | A positive Aβ status at baseline was associated with elevated anxiety symptoms; Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+ high-anxiety group. | Elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. | [154] |
| 2015/Cross-sectional study/Mild Dementia (n = 55), Moderate Dementia (n = 17), Severe Dementia (n = 20) | 58.8(4.1); 58.8(3.7); 59.7(3.1) | Japan/Kumamoto University Hospital/Clinic | NPI/MRI | Scores of the anxiety increased significantly with increased dementia severity. | Hallucinations, depression, and anxiety showed different patterns in EOAD. | [155] |
| 2017/None /EOAD (n = 16), NCs (n = 19) | 57.6 (4.2); 55.9(8.9) | USA/Greater Los Angeles Healthcare Center/Clinic | NPI/- | On the Neuropsychiatric Inventory, the ORs among the EOAD patients significantly correlated with anxiety scores. | Anxiety in mild EOAD may be associated with widening attentional refocusing to socioemotional stimuli, possibly reflecting decreased sensorimotor gating in the entorhinal cortex. | [156] |
| 2018/Longitudinal study/Community-dwelling, cognitively normal elderly individuals (n=270) | 73.6(6.1) | USA/Harvard Aging Brain Study/Community sample | Anxiety-concentration cluster/PiB-PET, Hollingshead score, AMNART | Higher PiB binding also predicted steeper rates of increase for anxiety-concentration scores. | A direct or indirect association of elevated amyloid beta levels with worsening anxious-depressive symptoms and support the hypothesis that emerging neuropsychiatric symptoms represent an early manifestation of preclinical Alzheimer's disease. | [157] |
| 2019/Longitudinal study/No AD (n=3968), Incident AD(n=87) | 72.83(9.03); 83.72(7.13) | Spain/Zaragoza Dementia and Depression project/Population-based | GMS-AGECAT/- | Significant association between anxiety cases at baseline and AD risk in the univariate analysis that persisted in the fully adjusted model; No significant association between 'subcases' of anxiety at baseline and AD risk was found. | Late-life, clinically significant anxiety (but not subclinical anxiety) seems to increase the risk of AD, independently of the effect of several confounders, including depression. | [158] |
| 2019/None/EOAD(n=24), LOAD(n=56) | 59.3(6.0), 82.3(4.9) | UK/Memory services of the South London and Maudsley NHS Foundation Trust /Clinic | NPI/- | Participants with EOAD were significantly worse on anxiety subscales. | The NPS severity was similar between EOAD and LOAD although EOAD had higher symptom prevalence and career distress. | [159] |
| 2020/Longitudinal study/CU(n=104), MCI(n=53) | 52(50.0); 22(41.5) |
Sweden/Swedish BioFINDER study/Clinic | HADS/MRI, Amyloid PET scanning | Apathy and anxiety were shown related to Aβ deposition and predicted cognitive decline; Anxiety also interacted with amyloid status to predict faster cognitive deterioration. | The associations between apathy and anxiety with Aβ deposition and cognitive decline point to these symptoms as early clinical manifestations of Alzheimer's disease. | [160] |
DSM-IV: the diagnostic and statistical manual of mental disorders, 4th ed; CT: computed tomography; ADL: activities of daily living; VaD: vascular dementia; FTD: frontotemporal dementia; NPI: neuropsychiatric inventory; NINCDS-ADRDA: The National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; a-MCI: amnestic mild cognitive impairment; Ade: early Alzheimer’s disease; Adm: moderate Alzheimer’s disease; VBM: voxel-based-morphometry; MRI: Magnetic resonance imaging; NPI-Q: neuropsychiatric inventory questionnaire; BPS: behavioral and psychological symptoms; EOAD: early-onset Alzheimer disease; LOAD: late-onset Alzheimer disease; HADS: hospital anxiety and depression scale; PET: positron emission tomography; AMNART: American national adult reading test; GMS-AGECAT: Geriatric mental state schedule- automated geriatric examination for computer assisted taxonomy.