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Study of the Spectrum of Treatable Dementias: Insights from a Large South Asian Cohort (TREAT-Dem Study)
Published online by Cambridge University Press: 30 May 2025
Abstract
Background and Purpose:
Dementia affects millions globally, with a subset of cases potentially reversible. This study evaluates the incidence, clinical markers and treatment outcomes of reversible dementias (ReDem).
Method:
This retrospective study included 370 ReDem cases from 1810 dementia patients. The ReDem cohort was split into potentially reversible dementias (PRD) and dual etiology (DE) groups. PRD encompassed secondary, potentially treatable dementia conditions, while DE included primary degenerative dementia (DD) with ≥1 uncontrolled comorbidity or new disease that worsened symptoms.
Results:
ReDem cases comprised 20.4% (n = 370 out of 1810) of dementia patients, with ReDem patients being younger (mean 56.2 vs. 61.9 years, p < 0.001) and exhibiting shorter illness durations than DD patients (p < 0.001). Key red flags, including young age (<45 years) at onset (DD = 8.6% vs. ReDem = 18.1%), fluctuation in symptoms (DD = 3.4% vs. ReDem = 11.6%), rapid cognitive decline (DD = 6.9% vs. ReDem = 18.4), high-risk exposures (DD = 0.1% vs. ReDem = 0.8%), high-risk behavior (DD = 0.1% vs. ReDem = 2.4%) and incongruent neuropsychological findings(DD = 1.0% vs. 12.7%), were significantly more frequent in ReDem cases (p < 0.05). Odds increased with each red flag present (≥1: OR = 5.94; ≥2: OR = 20.69; ≥3: OR = 25.14, p < 0.05). Reversible etiologies included immune (20.0%), neuroinfectious (6.6%), psychiatric (7.6%), nutritional/metabolic (10.5%), neurosurgical (14.6%) and other causes (12.2%). Of the 41% (152/370) followed, 19 expired, 63.9% (85/133) reported subjective improvement, and 31.6% (42/133) showed clinical dementia rating improvement.
Discussion and Conclusion:
This large-scale study underscores the importance of comprehensive diagnostic evaluations for ReDem. Identifying and treating reversible conditions and comorbidities in DD can improve patient outcomes, emphasizing the need for thorough evaluations in memory clinics and targeted interventions in dementia care.
Résumé
Étude sur le spectre des formes traitables de démence : nouvel éclairage d’une étude de cohorte importante, réalisée en Asie du Sud (TREAT-Dem Study).
La démence affecte des millions de personnes au monde, dont un sous-groupe souffrirait d’une forme potentiellement réversible. L’étude ici décrite visait à évaluer l’incidence et les marqueurs cliniques de ces formes de démence réversible (DR) ains que les résultats des traitements.
Il s’agit d’une étude rétrospective, comptant 370 cas de démence réversible sur 1810 cas de démence. La cohorte de DR a été divisée en deux groupes : démence potentiellement réversible (DPR) et coexistence de causes (CC). Le premier (DPR) comprenait des cas ayant des causes de démence secondaire, potentiellement traitables, tandis que le second (CC) comprenait des cas de démence dégénérative primitive, accompagnée d’au moins 1 maladie coexistente non maîtrisée ou d’une nouvelle maladie aggravant les symptômes.
Les cas de DR représentaient 20,4 % des patients atteints de démence (n = 370 sur 1810); les personnes atteintes de DR étaient plus jeunes (âge moyen : 56,2 ans contre [c.] 61,9 ans; p < 0,001) et la durée de la maladie était plus courte que celle observée chez les patients atteints de démence dégénérative (DD) (p < 0,001). Les principaux signes faisant soulever des doutes, notamment un jeune âge (< 45 ans) au début de la maladie (DD = 8,6 % c. DR = 18,1 %), la variabilité des symptômes (DD = 3,4 % c. DR = 11,6 %) de déclin cognitif rapide (DD = 6,9 % c. DR = 18,4), l’exposition à des substances à risque élevé (DD = 0,1 % c. DR = 0,8 %), des comportements à risque élevé (DD = 0,1 % c. DR = 2,4 %) et des résultats neuropsychologiques incompatibles avec ceux de la maladie (DD = 1,0 % c. 12,7 %), étaient significativement plus fréquents dans le groupe de DR que dans l’autre (p < 0,05). Les probabilités augmentaient avec chacun des signes d’alarme (≥ 1 : risque relatif approché [RRA] = 5,94; ≥ 2 : RRA = 20,69; ≥ 3 : RRA = 25,14; p < 0,05). Quant aux facteurs de maladie réversible, ils comprenaient des causes immunitaires (20,0 %), neuro-infectieuses (6,6 %), psychiatriques (7,6 %), nutritionnelles ou métaboliques (10,5 %), neurochirurgicales (14,6 %) et autres (12,2 %). Sur les 41 % de sujets suivis (152/370), 19 sont morts; 63,9 % (85/133) ont fait état d’une amélioration subjective et 31,6 % (42/133) ont connu une amélioration des résultats sur l’échelle Clinical Dementia Rating.
Cette étude d’envergure souligne l’importance des évaluations diagnostiques approfondies dans la détection des cas de démences réversible. Ainsi, le fait de reconnaître et de traiter les affections réversibles et les maladies coexistentes dans les cas de démence dégénérative peut améliorer l’évolution de l’état de santé des patients, d’où la nécessité de procéder à des évaluations complètes dans les centres de consultation sur la mémoire et à des interventions ciblées dans la prestation des soins aux personnes atteintes de démence.
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- © The Author(s), 2025. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation
References
Nichols, E, Steinmetz, JD, Vollset, SE, etal. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease study 2019. Lancet Public Health. 2022;7:e105–25.10.1016/S2468-2667(21)00249-8CrossRefGoogle Scholar
Mercy, L, Hodges, JR, Dawson, K, Barker, RA, Brayne, C. Incidence of early-onset dementias in Cambridgeshire, United Kingdom. Neurology. 2008;71:1496–9.10.1212/01.wnl.0000334277.16896.faCrossRefGoogle ScholarPubMed
Rabinovici, GD, La Joie, R. Amyloid-targeting monoclonal antibodies for Alzheimer disease. JAMA. 2023;330:507–9.10.1001/jama.2023.11703CrossRefGoogle ScholarPubMed
Hahn, RD, Webster, B, Weickhardt, G, etal. Penicillin treatment of general paresis (dementia paralytica): results of treatment in 1,086 patients the majority of whom were followed for more than five years. AMA Arch Neurol Psychiatry. 1959;81:557–90.CrossRefGoogle Scholar
Adams, RD, Fisher, CM, Hakim, S, Ojemann, RG, Sweet, WH. Symptomatic occult hydrocephalus with normal cerebrospinal-fluid pressure. New Engl J Med. 2010;97:693–5.Google Scholar
Bello, VME, Schultz, RR. Prevalence of treatable and reversible dementias: a study in a dementia outpatient clinic. Dement Neuropsychol. 2011;5:44.CrossRefGoogle Scholar
Weytingh, MD, Bossuyt, PMM, van Crevel, H. Reversible dementia: more than 10% or less than 1%? - a quantitative review. J Neurol. 1995;242:466–71.10.1007/BF00873551CrossRefGoogle ScholarPubMed
Marsden, CD, Harrison, MJG. Outcome of investigation of patients with presenile dementia. Br Med J. 1972;2:249–52.10.1136/bmj.2.5808.249CrossRefGoogle ScholarPubMed
Clarfield, AM. The decreasing prevalence of reversible dementias: an updated meta-analysis. Arch Intern Med. 2003;163:2219–29.10.1001/archinte.163.18.2219CrossRefGoogle Scholar
Clarfield, AM. The reversible dementias: do they reverse? Ann Intern Med. 1988;109:476–86.10.7326/0003-4819-109-6-476CrossRefGoogle ScholarPubMed
Porsteinsson, AP, Isaacson, RS, Knox, S, Sabbagh, MN, Rubino, I. Diagnosis of early Alzheimer’s disease: clinical practice in 2021. Journal of Prevention of Alzheimer’s Disease. 2021;8:371–86.10.14283/jpad.2021.23CrossRefGoogle ScholarPubMed
Mekala, S, Paplikar, A, Mioshi, E, et al. Dementia diagnosis in seven languages: the Addenbrooke’s cognitive examination-III in India. Arch Clin Neuropsychol. 2020;35:528–38.10.1093/arclin/acaa013CrossRefGoogle ScholarPubMed
Morris, JC. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int Psychogeriatr. 1997;9 Suppl 1:173–6.10.1017/S1041610297004870CrossRefGoogle ScholarPubMed
Albert, MS, DeKosky, ST, Dickson, D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270–9.10.1016/j.jalz.2011.03.008CrossRefGoogle ScholarPubMed
McKeith, IG, Boeve, BF, Dickson, DW, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium. Neurology. 2017;89:88–100.10.1212/WNL.0000000000004058CrossRefGoogle ScholarPubMed
Emre, M, Aarsland, D, Brown, R, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22:1689–707.10.1002/mds.21507CrossRefGoogle ScholarPubMed
CDC. CJD Diagnostic Criteria | Classic CJD [Internet]. 2024: Accessed May 13, 2025. https://www.cdc.gov/creutzfeldt-jakob/hcp/clinical-overview/diagnosis.html.Google Scholar
Sachdev, P, Kalaria, R, O’Brien, J, et al. Diagnostic criteria for vascular cognitive disorders: a VASCOG statement. Alzheimer Dis Assoc Disord. 2014;28:206–18.10.1097/WAD.0000000000000034CrossRefGoogle ScholarPubMed
Armstrong, MJ, Litvan, I, Lang, AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80:496–503.CrossRefGoogle ScholarPubMed
Rascovsky, K, Hodges, JR, Knopman, D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.10.1093/brain/awr179CrossRefGoogle ScholarPubMed
Jack, CR, Bennett, DA, Blennow, K, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14:535–562.10.1016/j.jalz.2018.02.018CrossRefGoogle Scholar
Maletta, GJ. The concept of “Reversible”Dementia. J Am Geriatr Soc. 1990;38:136–40.CrossRefGoogle ScholarPubMed
Draper, B. Potentially reversible dementia: a review. Aust N Z J Psychiatry. 1991;25:506–18.10.3109/00048679109064444CrossRefGoogle ScholarPubMed
GOLD. GOLD report - global initiative for Chronic Obstructive lung disease. 2024. Accessed May 12, 2025. https://goldcopd.org/2024-gold-report/.Google Scholar
Joglar, JA, Chung, MK, Armbruster, AL, et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation. 2024;149:E1–156.CrossRefGoogle Scholar
Jonklaas, J, Bianco, AC, Bauer, AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on Thyroid hormone replacement. Thyroid. 2014;24:1670–1751.10.1089/thy.2014.0028CrossRefGoogle ScholarPubMed
Unger, T, Borghi, C, Charchar, F, et al. 2020 International society of hypertension global hypertension practice guidelines. J Hypertens. 2020;38:982–1004.CrossRefGoogle ScholarPubMed
Elsayed, NA, Aleppo, G, Aroda, VR, et al. 2. Classification and diagnosis of diabetes: standards of care in diabetes—2023. Diabetes Care. 2023;46:S19–40.10.2337/dc23-S002CrossRefGoogle ScholarPubMed
Day, GS. Reversible dementias. CONTINUUM Lifelong Learning in Neurology. 2019;25:234–53.CrossRefGoogle ScholarPubMed
Hejl, A, Høgh, P, Waldemar, G. Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry. 2002;73:390–4.CrossRefGoogle ScholarPubMed
Chandra, SR, Ray, S, Isaac, T, et al. A clinical TRIAD for early suspicion of autoimmune encephalitis as a possibility in patients presenting with progressive cognitive decline. Asian J Psychiatr. 2019;41:5–12.10.1016/j.ajp.2019.02.013CrossRefGoogle ScholarPubMed
Maria Eboli Bello, V, Rizek Schultz, R. Prevalence of treatable and reversible dementias a study in a dementia outpatient clinic. Dement Neuropsychol. 2011;5:44–7.10.1590/S1980-57642011DN05010008CrossRefGoogle Scholar
Marsden, CD, Harrison, MJG. Presenile dementia. Br Med J. 1972;3:50–51.10.1136/bmj.3.5817.50-bCrossRefGoogle ScholarPubMed
Freemon, FR, Rudd, SM. Clinical Features That Predict Potentially Reversible Progressive Intellectual Deterioration. J Am Geriatr Soc. 1982;30:449–51.10.1111/j.1532-5415.1982.tb03382.xCrossRefGoogle ScholarPubMed
Tripathi, M, Vibha, D. Reversible dementias. Indian J Psychiatry. 2009; 51(Suppl1): S52.Google ScholarPubMed
Bunn, F, Burn, AM, Goodman, C, etal. Comorbidity and dementia: a scoping review of the literature. BMC Med. 2014;12:192.10.1186/s12916-014-0192-4CrossRefGoogle ScholarPubMed
Ma, D, Wang, Y, Zhao, Y, etal. How to manage comorbidities in people with dementia: a scoping review. Ageing Res Rev. 2023;88:101937.10.1016/j.arr.2023.101937CrossRefGoogle ScholarPubMed
Klimkowicz-Mrowiec, A, Furgal, M, Slowik, A, Szczudlik, A. REVERSIBLE LIMBIC ENCEPHALITIS IN a PERSON WITH ALZHEIMER’S DISEASE. J Am Geriatr Soc. 2011;59:757–9.10.1111/j.1532-5415.2011.03340.xCrossRefGoogle Scholar
Chatterjee, S, Mudher, A. Alzheimer’s disease and Type 2 diabetes: a critical assessment of the shared pathological traits. Front Neurosci. 2018;12:383.10.3389/fnins.2018.00383CrossRefGoogle ScholarPubMed
Casserly, I, Topol, E. Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet. 2004;363:1139–46.10.1016/S0140-6736(04)15900-XCrossRefGoogle ScholarPubMed
Fu, P, Gao, M, Yung, KKL. Association of intestinal disorders with Parkinson’s disease and Alzheimer’s disease: a systematic review and meta-analysis. ACS Chem Neurosci. 2020;11:395–405.10.1021/acschemneuro.9b00607CrossRefGoogle ScholarPubMed
Cardoso, BR, Cominetti, C, Cozzolino, SMF. Importance and management of micronutrient deficiencies in patients with Alzheimer’s disease. Clin Interv Aging. 2013;8:531.10.2147/CIA.S27983CrossRefGoogle ScholarPubMed
Santiago, JA, Potashkin, JA. The impact of disease comorbidities in Alzheimer’s disease. Front Aging Neurosci. 2021;13:631770.CrossRefGoogle ScholarPubMed
Rudnicka-Drożak, E, Drożak, P, Mizerski, G, etal. Links between COVID-19 and Alzheimer’s disease—What do we already know? Int J Environ Res Public Health. 2023;20:2146.10.3390/ijerph20032146CrossRefGoogle ScholarPubMed
Dintica, CS, Calderón-Larrañaga, A, Vetrano, DL, Xu, W. Association between sensory impairment and dementia: the roles of social network and leisure activity. Journal of Alzheimer’s Disease. 2023;94:585–595.10.3233/JAD-230041CrossRefGoogle ScholarPubMed
Tadic, M, Cuspidi, C, Hering, D. Hypertension and cognitive dysfunction in elderly: blood pressure management for this global burden. BMC Cardiovasc Disord. 2016;16:1–9.10.1186/s12872-016-0386-0CrossRefGoogle ScholarPubMed
Wang, K, Zhao, S, Lee, EKP, etal. Risk of dementia among patients with diabetes in a multidisciplinary, primary care management program. JAMA Netw Open. 2024;7:e2355733–e2355733.CrossRefGoogle Scholar
Cholerton, B, Baker, LD, Montine, TJ, Craft, S. Type 2 diabetes, cognition, and dementia in older adults: toward a precision health approach. Diabetes Spectr. 2016;29:210–219.10.2337/ds16-0041CrossRefGoogle Scholar
Wieland, DR, Wieland, JR, Wang, H, etal. Thyroid disorders and dementia risk: a nationwide population-based case-control study. Neurology. 2022;99:E679–87.10.1212/WNL.0000000000200740CrossRefGoogle Scholar
Zhang, W, Liang, J, Li, C, etal. Age at diagnosis of atrial fibrillation and incident dementia. JAMA Netw Open. 2023;6:e2342744–e2342744.10.1001/jamanetworkopen.2023.42744CrossRefGoogle ScholarPubMed
Li, J, Wu, Y, Zhang, D, Nie, J, Onofrj, M. Associations between heart failure and risk of dementia: a PRISMA-compliant meta-analysis. Medicine. 2020;99:E18492.10.1097/MD.0000000000018492CrossRefGoogle ScholarPubMed
Wang, J, Li, X, Lei, S, etal. Risk of dementia or cognitive impairment in COPD patients: a meta-analysis of cohort studies. Front Aging Neurosci. 2022;14:9.Google Scholar
Lin, JC, Li, CH, Chen, YY, etal. Rhythm control better prevents dementia than rate control strategies in patients with atrial fibrillation—A nationwide cohort study. J Pers Med. 2022;12:12.Google ScholarPubMed
Müller-Schmitz, K, Krasavina-Loka, N, Yardimci, T, et al. Normal pressure hydrocephalus associated with Alzheimer’s disease. Ann Neurol. 2020;88:703–11.CrossRefGoogle ScholarPubMed
Flanagan, EP, Geschwind, MD, Lopez-Chiriboga, AS, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80:30–9.10.1001/jamaneurol.2022.4251CrossRefGoogle ScholarPubMed
Sashindran, VK, Aggarwal, V, Khera, A. Prevalence of vitamin B12 deficiency in elderly population (>60 years) presenting with dementia to outpatient department. Med J Armed Forces India. 2022;78:94–8.10.1016/j.mjafi.2020.11.003CrossRefGoogle ScholarPubMed
Bastiaansen, AEM, Van Steenhoven, RW, De Bruijn, MAAM, et al. Autoimmune encephalitis resembling dementia syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1039.10.1212/NXI.0000000000001039CrossRefGoogle ScholarPubMed
Morris, MC, Schneider, JA, Tangney, CC. Thoughts on B-vitamins and dementia. J Alzheimers Dis. 2006;9:429–33.CrossRefGoogle ScholarPubMed
Tripathi, M, Sheshadri, S, Padma, MV, Jain, S, Meheshwari, MC, Behari, M. Serum cobalamin levels in dementias. Neurol India. 2001;49:284–6.Google ScholarPubMed
Lindenbaum, J, Rosenberg, IH, Wilson, PWF, Stabler, SP, Allen, RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994;60:2–11.10.1093/ajcn/60.1.2CrossRefGoogle ScholarPubMed
Moore, E, Mander, A, Ames, D, Carne, R, Sanders, K, Watters, D. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr. 2012;24:541–56.10.1017/S1041610211002511CrossRefGoogle ScholarPubMed
Jatoi, S, Hafeez, DA, Riaz, SU, Ali, A, Ghauri, MI, Zehra, M. Low vitamin B12 levels: an underestimated cause of minimal cognitive impairment and dementia. Cureus. 2020;12(2):e6976.Google ScholarPubMed
Benyumiza, D, Kumakech, E, Gutu, J, et al. Prevalence of dementia and its association with central nervous system infections among older persons in northern Uganda: cross-sectional community-based study. BMC Geriatr. 2023;23:1–11.10.1186/s12877-023-04174-9CrossRefGoogle ScholarPubMed
Calcagno, A, Celani, L, Trunfio, M, et al. Alzheimer dementia in people living with HIV. Neurol Clin Pract. 2021;11:E627–33.10.1212/CPJ.0000000000001060CrossRefGoogle ScholarPubMed
Tai, XY, Torzillo, E, Lyall, DM, Manohar, S, Husain, M, Sen, A. Association of dementia risk with focal epilepsy and modifiable cardiovascular risk factors. JAMA Neurol. 2023;80:445–54.10.1001/jamaneurol.2023.0339CrossRefGoogle ScholarPubMed
Henderson, JB, Zarghouni, M, Hise, JH, Opatowsky, MJ, Layton, KF. Dementia caused by dural arteriovenous fistulas reversed following endovascular therapy. Proc (Bayl Univ Med Cent). 2012;25:338–340.Google ScholarPubMed
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