Hostname: page-component-6bb9c88b65-bw5xj Total loading time: 0 Render date: 2025-07-23T09:06:42.328Z Has data issue: false hasContentIssue false
  • English
  • Français

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

M.M. Samim Open the ORCID record for M.M. Samim [Opens in a new window] ,
Faheem Arshad Open the ORCID record for Faheem Arshad [Opens in a new window] ,
Pallavi N. Sastry ,
B.S. Keerthana ,
Aparna Somaraj ,
Sarath Govindaraj ,
Sandeep S. Kumar ,
Priya Treesa Thomas ,
Subasree Ramakrishnan  and
Anita Mahadevan
...Show all authors
M.M. Samim
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Faheem Arshad*
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Pallavi N. Sastry
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
B.S. Keerthana
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Aparna Somaraj
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Sarath Govindaraj
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Sandeep S. Kumar
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Priya Treesa Thomas
Affiliation:
Department of Psychiatric Social Work, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Subasree Ramakrishnan
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Anita Mahadevan
Affiliation:
Department of Neuropathology, Officer in Charge, Autoimmune Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
Suvarna Alladi
Affiliation:
Cognitive Neurosciences, Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India
*
Corresponding author: Faheem Arshad; Email: faheem2285@gmail.com
Get access Rights & Permissions [Opens in a new window]

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

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).

Contexte et but :

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.

Méthode :

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.

Résultats :

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.

Discussion et conclusion :

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.

Keywords

dementiadementia treatmentreversible cognitive impairmentreversible dementiatreatable dementia

Information

Type
Original Article
Information
Canadian Journal of Neurological Sciences , First View , pp. 1 - 11
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

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.Google 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.Google Scholar
Rabinovici, GD, La Joie, R. Amyloid-targeting monoclonal antibodies for Alzheimer disease. JAMA. 2023;330:507–9.Google Scholar
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.Google 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.Google 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.Google Scholar
Marsden, CD, Harrison, MJG. Outcome of investigation of patients with presenile dementia. Br Med J. 1972;2:249–52.Google Scholar
Clarfield, AM. The decreasing prevalence of reversible dementias: an updated meta-analysis. Arch Intern Med. 2003;163:2219–29.Google Scholar
Clarfield, AM. The reversible dementias: do they reverse? Ann Intern Med. 1988;109:476–86.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
Emre, M, Aarsland, D, Brown, R, et al. Clinical diagnostic criteria for dementia associated with Parkinson’s disease. Mov Disord. 2007;22:1689–707.Google Scholar
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.Google Scholar
Armstrong, MJ, Litvan, I, Lang, AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80:496–503.Google Scholar
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.Google Scholar
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.Google Scholar
Maletta, GJ. The concept of “Reversible”Dementia. J Am Geriatr Soc. 1990;38:136–40.Google Scholar
Draper, B. Potentially reversible dementia: a review. Aust N Z J Psychiatry. 1991;25:506–18.Google Scholar
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.Google 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.Google Scholar
Unger, T, Borghi, C, Charchar, F, et al. 2020 International society of hypertension global hypertension practice guidelines. J Hypertens. 2020;38:982–1004.Google Scholar
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.Google Scholar
Day, GS. Reversible dementias. CONTINUUM Lifelong Learning in Neurology. 2019;25:234–53.Google Scholar
Hejl, A, Høgh, P, Waldemar, G. Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry. 2002;73:390–4.Google Scholar
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.Google Scholar
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.Google Scholar
Marsden, CD, Harrison, MJG. Presenile dementia. Br Med J. 1972;3:50–51.Google Scholar
Freemon, FR, Rudd, SM. Clinical Features That Predict Potentially Reversible Progressive Intellectual Deterioration. J Am Geriatr Soc. 1982;30:449–51.Google Scholar
Tripathi, M, Vibha, D. Reversible dementias. Indian J Psychiatry. 2009; 51(Suppl1): S52.Google Scholar
Bunn, F, Burn, AM, Goodman, C, etal. Comorbidity and dementia: a scoping review of the literature. BMC Med. 2014;12:192.Google Scholar
Ma, D, Wang, Y, Zhao, Y, etal. How to manage comorbidities in people with dementia: a scoping review. Ageing Res Rev. 2023;88:101937.Google Scholar
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.Google 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.Google Scholar
Casserly, I, Topol, E. Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet. 2004;363:1139–46.Google Scholar
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.Google Scholar
Cardoso, BR, Cominetti, C, Cozzolino, SMF. Importance and management of micronutrient deficiencies in patients with Alzheimer’s disease. Clin Interv Aging. 2013;8:531.Google Scholar
Santiago, JA, Potashkin, JA. The impact of disease comorbidities in Alzheimer’s disease. Front Aging Neurosci. 2021;13:631770.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google 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.Google 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.Google Scholar
Zhang, W, Liang, J, Li, C, etal. Age at diagnosis of atrial fibrillation and incident dementia. JAMA Netw Open. 2023;6:e2342744–e2342744.Google Scholar
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.Google Scholar
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 Scholar
Müller-Schmitz, K, Krasavina-Loka, N, Yardimci, T, et al. Normal pressure hydrocephalus associated with Alzheimer’s disease. Ann Neurol. 2020;88:703–11.Google Scholar
Flanagan, EP, Geschwind, MD, Lopez-Chiriboga, AS, et al. Autoimmune encephalitis misdiagnosis in adults. JAMA Neurol. 2023;80:30–9.Google Scholar
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;78:94–8.60+years)+presenting+with+dementia+to+outpatient+department.+Med+J+Armed+Forces+India.+2022;78:94–8.>Google Scholar
Bastiaansen, AEM, Van Steenhoven, RW, De Bruijn, MAAM, et al. Autoimmune encephalitis resembling dementia syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(5):e1039.Google Scholar
Morris, MC, Schneider, JA, Tangney, CC. Thoughts on B-vitamins and dementia. J Alzheimers Dis. 2006;9:429–33.Google Scholar
Tripathi, M, Sheshadri, S, Padma, MV, Jain, S, Meheshwari, MC, Behari, M. Serum cobalamin levels in dementias. Neurol India. 2001;49:284–6.Google Scholar
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.Google Scholar
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.Google Scholar
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 Scholar
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.Google Scholar
Calcagno, A, Celani, L, Trunfio, M, et al. Alzheimer dementia in people living with HIV. Neurol Clin Pract. 2021;11:E627–33.Google Scholar
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.Google Scholar
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 Scholar
Supplementary material: File

Samim et al. supplementary material

Samim et al. supplementary material
Download Samim et al. supplementary material(File)
File 22.9 KB