Neuropsychiatric Symptoms as Predictors of Progression to Severe Alzheimer’s Dementia and Death: The Cache County Dementia Progression Study
Open accessAbstract
OBJECTIVE: Little is known about factors influencing the rate of progression of Alzheimer's dementia. Using data from the Cache County Dementia Progression Study, the authors examined the link between clinically significant neuropsychiatric symptoms in mild Alzheimer's dementia and progression to severe dementia or death. METHOD: The Cache County Dementia Progression Study is a longitudinal study of dementia progression in incident cases of this condition. Survival analyses included unadjusted Kaplan-Meier plots and multivariate Cox proportional hazard models. Hazard ratio estimates controlled for age at dementia onset, dementia duration at baseline, gender, education level, General Medical Health Rating, and apolipoprotein E epsilon 4 genotype. RESULTS: Three hundred thirty-five patients with incident Alzheimer's dementia were studied. Sixty-eight (20%) developed severe dementia over the follow-up period. Psychosis (hazard ratio=2.007), agitation/aggression (hazard ratio=2.946), and any one clinically significant neuropsychiatric symptom (domain score ≥4, hazard ratio=2.682) were associated with more rapid progression to severe dementia. Psychosis (hazard ratio=1.537), affective symptoms (hazard ratio=1.510), agitation/aggression (hazard ratio=1.942), mildly symptomatic neuropsychiatric symptoms (domain score of 1-3, hazard ratio=1.448), and clinically significant neuropsychiatric symptoms (hazard ratio=1.951) were associated with earlier death. CONCLUSIONS: Specific neuropsychiatric symptoms are associated with shorter survival time from mild Alzheimer's dementia to severe dementia and/or death. The treatment of specific neuropsychiatric symptoms in mild Alzheimer's dementia should be examined for its potential to delay time to severe dementia or death.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The clinical distinction between fvAD and bvFTD has implications for prognosis, treatment, disease progression, and caregiver burden.
“The appropriate clinical distinction between fvAD and bvFTD has implications for prognosis, treatment, disease progression, and caregiver burden [11–15].”
From Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road (2017) · cites this paper as [12]
The Discussion (page unavailable) reports that early agitation/aggression in Alzheimer’s dementia predicted accelerated progression and mortality, supporting the general point that symptoms matter for prognosis. The paper does not address the clinical distinction between fvAD and bvFTD or show that making that distinction affects treatment or caregiver burden. (LLM, conf=0.78)
Experimental — accuracy not yet measuredIndividuals with mild cognitive impairment who also have neuropsychiatric symptoms are at risk of faster progression to dementia.
“There is some evidence that individuals with mild cognitive impairment who also have neuropsychiatric symptoms are at risk of faster progression to dementia 118 .”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [118]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,803 · see citing works
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,003 · see citing works
A New Clinical Scale for the Staging of Dementia
Hughes, C. P., Berg, L., Danziger, W., Coben, L. A., & Martin, R. L. (1982) · British Journal of Psychiatry · doi:10.1192/bjp.140.6.566 · Cited by 7,056 · see citing works
Clarifying Confusion: The Confusion Assessment Method: A New Method for Detection of Delirium
Inouye, S. K., van Dyck, C. H., Alessi, C. A., Balkin, S., Siegal, A. P., & Horwitz, R. I. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-12-941 · Cited by 5,250 · see citing works
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069 · see citing works
The Neuropsychiatric Inventory
Cummings, J. L. (1997) · Neurology · doi:10.1212/wnl.48.5_suppl_6.10s · Cited by 2,017 · see citing works
Witlox, J., Eurelings, L. S. M., de Jonghe, J. F. M., Kalisvaart, K. J., Eikelenboom, P., & van Gool, W. A. (2010) · JAMA · doi:10.1001/jama.2010.1013 · Cited by 1,972 · see citing works
Lyketsos, C. G., Steinberg, M. I., Tschanz, J. T., Norton, M. C., Steffens, D. C., & Breitner, J. C. S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.5.708 · Cited by 1,125 · see citing works
Self-citation2012 Alzheimer's disease facts and figures Alzheimer's Association ∗
Thies, W. H., & Bleiler, L. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.02.001 · Cited by 984 · see citing works
Breitner, J. C. S., Wyse, B. W., Anthony, J. C., Welsh-Bohmer, K. A., Steffens, D. C., Norton, M. C., Tschanz, J. T., Plassman, B. L., Meyer, M. R., Skoog, I., et al. (1999) · Neurology · doi:10.1212/wnl.53.2.321 · Cited by 397 · see citing works
Self-citationPredicting Time to Nursing Home Care and Death in Individuals With Alzheimer Disease
Stern, Y. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340040030 · Cited by 359 · see citing works
Lyketsos, C. G., Colenda, C. C., Beck, C. M., Blank, K., Doraiswamy, M. P., Kalunian, D. A., & Yaffe, K. S. (2006) · American Journal of Geriatric Psychiatry · doi:10.1097/01.jgp.0000221334.65330.55 · Cited by 275 · see citing works
Self-citationTschanz, J. T., Corcoran, C. D., Schwartz, S., Treiber, K., Green, R. C., Norton, M. C., Mielke, M. M., Piercy, K., Steinberg, M., Rabins, P. V., et al. (2011) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e3181faec23 · Cited by 244 · cited 7× · see citing works
“Acknowledgments Grant Support: This research was supported by the Cache County Memory Study, Dementia Progression Study, and the Joseph and Kathleen Bryan ADRC: R01AG11380, R01AG21136, R01AG18712.”
MethodInfluentialSelf-citationAtypical Antipsychotic Use in Patients With Dementia: Managing Safety Concerns
Steinberg, M., & Lyketsos, C. G. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12030342 · Cited by 209 · see citing works
Self-citationRates of progression in mild cognitive impairment and early Alzheimer’s disease
Storandt, M., Grant, E., Miller, J. P., & Morris, J. C. (2002) · Neurology · doi:10.1212/wnl.59.7.1034 · Cited by 202 · see citing works
Lyketsos, C. G., Galik, E. M., Steele, C., Steinberg, M., Rosenblatt, A., Warren, A., Leoutsakos, J., Baker, A. S., & Brandt, J. (1999) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1999.tb07245.x · Cited by 182 · see citing works
Self-citationPeters, M. E., Rosenberg, P. B., Steinberg, M., Norton, M. C., Welsh-Bohmer, K. A., Hayden, K. M., Breitner, J., Tschanz, J. T., & Lyketsos, C. G. (2013) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2013.01.049 · Cited by 167 · see citing works
Self-citationRabins, P. V., Lyketsos, C. G., & Steele, C. D. (2006) · Oxford University Press eBooks · doi:10.1093/med/9780195169782.001.0001 · Cited by 146 · see citing works
Self-citationFranch, J. V., Calvó‐Perxas, L., Garre‐Olmo, J., Garriga, O. T., & Pousa, S. L. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120913 · Cited by 91 · see citing works
Predictors of progression to severe Alzheimer's disease in an incidence sample
Rabins, P. V., Schwartz, S., Black, B. S., Corcoran, C. D., Fauth, E. B., Mielke, M. M., Christensen, J., Lyketsos, C. G., & Tschanz, J. T. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.01.003 · Cited by 70 · see citing works
Self-citationPredicting cognitive decline in Alzheimer's disease: An integrated analysis
López, O. L., Schwam, E. M., Cummings, J. L., Gauthier, S. G., Jones, R. W., Wilkinson, D. G., Waldemar, G., Zhang, R. H., & Schindler, R. J. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.04.003 · Cited by 43 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ismail, Z., Smith, E. E., Geda, Y., Sultzer, D., Brodaty, H., Smith, G., Agüera‐Ortiz, L., Sweet, R., Miller, D., Lyketsos, C. G., et al. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.05.017 · Cited by 818 · see citing works
Self-citationIsmail, Z., for the NPS Professional Interest Area of the International Society of to Advance Alzheimer’s Research and Treatment (NPS-PIA of ISTAART), Agüera-Ortiz, L., Brodaty, H., Cieslak, A., Cummings, J., Fischer, C. E., Gauthier, S., Geda, Y. E., Herrmann, N., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-160979 · Cited by 530 · see citing works
Self-citationReynolds, C. F., Jeste, D. V., Sachdev, P. S., & Blazer, D. G. (2022) · World Psychiatry · doi:10.1002/wps.20996 · Cited by 465 · see citing works
Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms
Lanctôt, K. L., Amatniek, J., Ancoli‐Israel, S., Arnold, S. E., Ballard, C., Cohen‐Mansfield, J., Ismail, Z., Lyketsos, C., Miller, D. S., Musiek, E., et al. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.07.001 · Cited by 395 · see citing works
Self-citationNeuropsychiatric symptoms in Alzheimer's disease: what might be associated brain circuits?
Rosenberg, P. B., Nowrangi, M. A., & Lyketsos, C. G. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2015.05.005 · Cited by 302 · see citing works
Self-citationDuara, R., & Barker, W. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01185-z · Cited by 187 · see citing works
Watt, J. A., Goodarzi, Z., Veroniki, A. A., Nincic, V., Khan, P. A., Ghassemi, M., Thompson, Y., Tricco, A. C., & Straus, S. E. (2019) · Annals of Internal Medicine · doi:10.7326/m19-0993 · Cited by 159 · see citing works
Boutoleau-Bretonnière, C., Pouclet-Courtemanche, H., Gillet, A., Bernard, A., Deruet, A. L., Gouraud, I., Mazoue, A., Lamy, E., Rocher, L., Kapogiannis, D., et al. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-200604 · Cited by 151 · see citing works
Watt, J. A., Goodarzi, Z., Veroniki, A. A., Nincic, V., Khan, P. A., Ghassemi, M., Lai, Y., Treister, V., Thompson, Y., Schneider, R., et al. (2021) · BMJ · doi:10.1136/bmj.n532 · Cited by 143 · see citing works
Trial of pimavanserin in dementia-related psychosis
Tariot, P. N., Cummings, J. L., Soto-Martin, M. E., Ballard, C., Erten-Lyons, D., Sultzer, D. L., Devanand, D. P., Weintraub, D., McEvoy, B., Youakim, J. M., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2034634 · Cited by 145 · see citing works
Suárez-González, A., Rajagopalan, J., Livingston, G., & Alladi, S. (2021) · EClinicalMedicine · doi:10.1016/j.eclinm.2021.101047 · Cited by 130 · see citing works
Goukasian, N., Hwang, K. S., Romero, T., Grotts, J., Do, T. M., Groh, J. R., Bateman, D. R., & Apostolova, L. G. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-031947 · Cited by 64 · see citing works
Lichtwarck, B., Selbaek, G., Kirkevold, Ø., Rokstad, A. M. M., Benth, J. Š., Lindstrøm, J. C., & Bergh, S. (2018) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2017.05.015 · Cited by 59 · see citing works
Aigbogun, M. S., Stellhorn, R., Hartry, A., Baker, R. A., & Fillit, H. (2019) · BMC Neurology · doi:10.1186/s12883-019-1260-3 · Cited by 46 · see citing works
Santacruz Escudero, J. M., Beltrán, J., Palacios, Á., Chimbí, C. M., Matallana, D., Reyes, P., Perez-Sola, V., & Santamaría-García, H. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00176 · Cited by 41 · see citing works
Diagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road
Sawyer, R. P., Rodriguez-Porcel, F., Hagen, M., Shatz, R., & Espay, A. J. (2017) · Journal of Clinical Movement Disorders · doi:10.1186/s40734-017-0052-4 · Cited by 40 · see citing works
Liew, T. M. (2021) · Age and Ageing · doi:10.1093/ageing/afab044 · Cited by 38 · see citing works
Lee, J. S., Kim, J. H., & Lee, S.-K. (2020) · Psychiatry Investigation · doi:10.30773/pi.2020.0009 · Cited by 25 · see citing works
Pirker-Kees, A., Dal-Bianco, P., & Schmidt, R. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181102 · Cited by 17 · see citing works
Pharmacotherapeutic combinations for the treatment of Alzheimer’s disease.
Nagata, T., Shinagawa, S., Nakajima, S., Noda, Y., & Mimura, M. (2022) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2022.2042514 · Cited by 11 · see citing works
- Authors
- Peters, M. E., Schwartz, S., Han, D., Rabins, P. V., Steinberg, M., Tschanz, J. T., & Lyketsos, C. G.
- Affiliations
- Utah State University (US)
- Corresponding author
- Lyketsos, Constantine G.
- Venue
- American Journal of Psychiatry
- Published
- 2015-05-01
- Volume
- 172
- Issue
- 5
- Pages
- 460-465
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4416978
- OpenAlex
- W2021809156
- Cited by
- 400
- References
- 25
- Citations by year
- 2026: 27 · 2025: 53 · 2024: 50 · 2023: 40 · 2022: 42 · 2021: 36 · 2020: 39 · 2019: 39 · 2018: 22 · 2017: 25 · 2016: 14 · 2015: 11
- FWCI
- 19.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01 AG 11380, R01AG011380, R01AG021136, R01AG018712, R01 AG18712, P50AG005146, R01 AG 21136, T32AG027668)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative Care and End-of-Life Issues
- Keywords
- Alzheimer's disease, neuropsychiatric symptoms, dementia progression, psychosis, agitation, aggression, affective symptoms, mortality, advanced dementia, mild dementia, survival analysis, APOE ε4
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Severity of Illness Index, Utah, Prevalence, Proportional Hazards Models, Disease Progression, Kaplan-Meier Estimate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
