Clinical practice guidelines on addressing cognitive impairment in treatable dementias.

INTRODUCTION

In older adults aged 60 years or above the prevalence of dementia in India is 7.4%, which translates to about 8.8 million cases of dementia.[ 1 ] With an estimated increase in the proportion of older adults aged over 60 years to approximately one-fifth of the entire population by 2050 due to increasing lifespan, the prevalence of dementia is predicted to increase tremendously.[ 2 ] A proportion of these dementias are considered to be produced by irreversible conditions, while the others by reversible conditions.

The precise frequency of reversible dementias in the general population is difficult to estimate. This is because of the ambiguity surrounding the terminology used to characterize reversible dementia—the variation in the population being studied, or the existence of subclinical instances that are difficult to diagnose.[ 3 ] By and large however, the proportion of reversible dementias compared to the irreversible dementias is very low. Prevalence is highly variable, with a varied number of studies reporting a range between 0 and 40%, and average approximates to 12%. While, the prevalence of potentially reversible aetiology has been reported 18% in patients under the age of 65 years, however only 5% in those over 65 years.[ 3 ] A meta-analysis showed that although potentially reversible causes were seen in 9% of the cases, only 0.6% of dementia cases could be reversed.[ 4 ] Optimum assessment of differential diagnosis and prompt treatment are therefore of paramount importance.

While therapeutic strategies are available for both reversible and irreversible dementias, the term ‘treatable dementias’ is assumed to be synonymous with ‘reversible dementias’ as they are ‘readily treatable’.[ 5 ] However, ‘treatable dementias’ include cases with conditions which are irreversible too.[ 6 ] There are definite ‘treatable aspects of irreversible dementias, such as behavioural and psychological symptoms of dementia.[ 6 ] This guideline does not cover those aspects.

The process of developing this guideline began with the identification of team members and establishment of the team. The team then determined the scope of the guideline in consultation with the clinical practice committee members, in particular to make sure there are no significant overlaps between the various guidelines of the issue. A framework or a content index was then developed. A systematic literature search was then conducted using specific search terms, independently by two of its members. The final list of articles to be reviewed was then determined by the lead member. The articles retrieved were classified into various framework heads and sub-heads. All members were then involved in documenting the review and the guidelines.

CAUSES OF POTENTIALLY REVERSIBLE DEMENTIAS

Little (2018) proposed a mnemonic DEMENTIAS for potentially reversible causes of dementia- D rugs, E yes/ E ars (sensory isolation), M etabolic, E motion, N ormal Pressure Hydrocephalus (NPH), T umour, I nfection, A trial Fibrillation/ A lcoholism and S leep Apnoea [Also see Figure 1 ].[ 5 ] We recommend adding A utoimmune (for A) also to the list.

However, for better understanding the reversible dementias can be broadly classified as:[ 6 , 7 ] 1. Intracranial (neurosurgical) disorders; 2. Intracranial (neuroinfectious) disorders; 3. Systemic (including metabolic/endocrinal) disorders; 4. toxic disorders and 5. mental and behavioural (psychiatric) disorders.

Depression, alcohol-induced cognitive impairment, normal pressure hydrocephalus (NPH), Vitamin B12 deficiency alone would account for more than half of causes of reversible dementias. Other less common causes are tumours and chronic subdural hematomas, hypothyroidism and central nervous system (CNS) infections such as neurosyphilis and HIV.[ 8 ] The autoimmune dementia and encephalopathies (ADE) are becoming increasingly prevalent in early onset dementia patients; about 20-25% in dementia of early onset.[ 9 ]

CLINICAL FEATURES OF POTENTIALLY REVERSIBLE DEMENTIAS

Potentially reversible dementias can be identified and differentiated from irreversible dementias from their clinical presentation. A thorough history often clinches the diagnosis of the underlying condition. Tables 1a - 1f show the list of disorders in each of the classified reversible dementia subtypes as mentioned above and their clinical features.

CLINICAL COURSE OF “TREATABLE DEMENTIAS”

In this section, we briefly describe the course of some of the highly prevalent causes of “treatable dementia” below:

Alcohol-induced (related) dementia

Several lines of research suggest that chronic consumption of alcohol leads to permanent damage, both structural and functional, to the brain. Apart from the indirect contribution of thiamine deficiency to this, alcohol too has direct effects—the presentation is named ‘alcohol related dementia (ARD)’. The umbrella term ‘alcohol-related brain damage’ includes both ARD and the Wernicke–Korsakoff syndrome. Patients with ARD are mostly male, have their onset of symptoms younger compared to other dementias and lack social support. Visuospatial, memory and executive dysfunction are mainly evident.[ 10 ]

Depressive cognitive disorder (Depressive pseudodementia)

Depressive cognitive disorder is characterised by a cognitive impairment where its ‘risk factors overlap with those for depression’. The symptoms mimic dementia, but improve with improvements in mood; there is no neuronal degeneration noted. It is prevalent in those aged 50 or above years. The cognitive domains mainly affected are: memory, executive function and speech. Although it may be difficult to diagnose depressive cognitive disorder when there is a significant overlap of depressive and true dementia symptoms, there are aspects that help differentiate it from true dementias.

The onset of cognitive impairment in depressive cognitive disorder is abrupt to acute and usually is precipitated and aggravated by stress. The symptoms show rapid progression as well as fast resolution. There is possibility of previous and family history of mood disorder episodes. More characteristically, they often tend to respond with ‘I do not know’ rather than confabulations, which are noted in other forms of dementia. Other symptoms of depression will be noted.[ 11 ] Table 2 shows the differences between depressive cognitive disorder and dementia.

Autoimmune dementia and encephalopathies (ADE)

ADE is broadly divided in paraneoplastic (underlying cancers) and non-paraneoplastic varieties. The non-neoplastic ADEs were considered idiopathic until recently where there has been discovery of many neural-specific autoantibodies.[ 9 ] The various varieties of common autoimmune encephalitis presenting as dementia[ 12 ] are given Table 3 . A detailed list of neural antibodies, in general, is given by Fernández-Fournier (2022)[ 13 ] Except for conditions like limbic encephalitis where the onset can be abrupt to acute, other conditions run a subacute to chronic course. While memory loss is the most prominent clinical presentation, other cognitive domains, especially attention is also affected. Preservation of memory with behavioural changes such as personality changes and social disinhibition may also be presented and mimic frontotemporal dementia. The course of ADE may be continuous or remitting and relapsing. Spontaneous recovery is also seen in some cases. Once the clinical suspicion is made and investigations show evidence of autoimmunity, the progression, or rather response to steroids and antibody-depleting agents (immunotherapy) is remarkably positive. Relapse after immunotherapy should be looked as a complication of immunotherapy-infectious complications such as progressive multifocal leukoencephalopathy or steroid-induced cognitive impairment.

Normal pressure hydrocephalic dementia

The classical triad of NPH is gait disorder, urinary dyscontrol and dementia. The following examination and historical characteristics support hydrocephalus as the cause of dementia: a history of urinary symptoms (frequency and/or incontinence not related to the urological system), a history of typical gait (wide-based, magnetic, ‘freezing’ gait, with postural instability), and a history of meningitis or subarachnoid haemorrhage of any cause at any point in the past (e.g., head trauma or aneurysmal bleeding). A large volume lumbar puncture is typically part of the evaluation process for hydrocephalus, ideally accompanied by a filmed gait analysis both prior to and in the hours that follow. Following the evacuation of 35 to 50 cc of CSF, improvements in urine and gait are suggestive of possible dementia reversibility.

Over a few years, dementia gradually worsen, albeit more subacute presentations do happen. There may be fluctuations in the course which might invite uncertainties., The neurosurgical installation of a ventriculoperitoneal or ventriculoatrial shunt may offer some reversal of dementia symptoms (especially in more obese people). Improvement in clinical outcomes is reported in 70% to 90% of those with confirmed NPH. However, there may frequently be concurrent neurodegeneration (Alzheimer’s disease, vascular or frontotemporal type) confounding the improvement. Interestingly, shunting may initially improve memory and gait abnormalities and postpone the deposition of beta-amyloid, but it is unlikely to totally stop the progression of the disease.

Metabolic dementias

Cortical ischemia, vascular dementia and cognitive decline have all been linked to abnormal thyroid function tests.

Specifically, higher thyroid-stimulating hormone and decreased thyroxine levels have been detected. But the evidence is conflicting. And there is scant data to support that hypothyroidism is the only cause of dementia or that the use of thyroid hormone replacement therapy could reverse cognitive impairment. Similarly, hyperthyroidism is linked to an increased risk of Alzheimer’s disease brain pathology due to greater thyroxine levels; however, there is minimal evidence that treating these abnormalities may enhance cognition. It is still advised to test thyroid function in the workup of cognitive impairment, even though more evidence is required to confirm the relationship between thyroid disease and dementia and the effects of treatment. This is because thyroid disease can result in other problems, such as depression, weight loss or cardiac arrhythmias, that can affect functional trajectories in dementia.[ 14 ]

Cognitive decline and dementia have been linked to both hypoparathyroidism resulting in hypocalcaemia and hyperparathyroidism resulting in hypercalcemia. Improved mentation has been linked to correction of the parathyroid abnormalities with parathyroid resection (hyperparathyroid) or calcitriol (hypoparathyroid). Importantly, lithium may stimulate PTH secretion resulting in hypercalcemia in around 10% of case and ensuing neuropsychiatric sequelae.

Severe deficiencies in vitamin B12 and folate are linked to anaemia and cognitive impairment since they are essential for healthy brain development. Malabsorption combined with a decrease in oral intake is the most common cause of vitamin B12 insufficiency in elders. Vit B12 deficiency is also more often seen in those receiving proton pump inhibitors, H2 blockers and or metformin in clinical context. Folate deficiency is more commonly seen in nutritional disorders, those with duodenal pathology, patients having chronic haemolytic anaemia, patients receiving antimetabolite agents such as methotrexate. Even in the absence of anaemia, a folate shortage can result in elevated homocysteine levels, which are linked to the pathophysiology of Alzheimer’s disease and vascular disease. Regretfully, metanalyses have not discovered a statistically significant improvement in mood or cognition associated with vitamin B12 or folate replacement. Alcohol misuse is also linked to deficiencies in B12, folate and niancin (vitamin B6). As per naturalistic studies following treatment for a vitamin B12 deficiency, neuropsychiatric symptoms recovery frequently takes longer to manifest (e.g., beginning to improve in around three months and lasting up to a year). Duration of untreated period of deficiency becomes critical as it may determine the irreversibility of the symptoms. Interestingly, some experts have pointed out a period of worsening before clinical improvement during supplementation.

A niacin deficiency is also linked to dementia, which is completely reversible once replenished.

Intracranial Tumours

Prior to twentieth-century imaging, dementia brought on by an undetected brain neoplasm was more typical. Now that neuroimaging techniques have become widely available in clinical practice, it is typically possible to quickly identify the brain lesions that cause dementia. Usually, a diffuse white matter, frontal or right hemisphere process is responsible for a subacute alteration in mentation that affects everyday functioning. Astrocytomas (glioblastomas) and meningiomas with oedema are the most prevalent because of the mass effect and increasing oedema that lead to abnormal mental status. Steroids are usually used to delay the onset of dementia caused by these lesions, which is then treated with surgery, radiation and/or chemotherapy.

Other toxic disorders

These dementia conditions might reverse with confiscation of the source of exposure, and subsequent clearance of the toxic substance from the body, whether by course of time or via the aid of therapeutic moieties [see Table 1d ]. The dementia may reverse partially or completely if the harmful exposure is stopped. Chelation therapy helps speed up recovery from heavy metal poisoning.

Sensitivity of drugs may increase (benzodiazepines or narcotics) or decrease (drugs mediated by beta-adrenergic receptors) with age. So, the response in terms of any confusion or memory or cognition in context to any medication can be unpredictable and prompt an investigation into a possible medication reaction. Most of the medications implicated in inducing dementia like those for atopy, upper respiratory infections, urinary incontinence do so via their anti-cholinergic burden. Other group of medications which cause CNS depression and are related to cognitive deficits are benzodiazepines.

Traumatic brain injury-related cognitive impairment is described in clinical practice guidelines on TBI.[ 15 ]

Table 4 lists the various criteria’s and tools to help clinicians to identify and de-prescribe the offending drugs. Again, dementia would significantly improve once the offending agent is stopped.

Cognitive assessment

There are several screening tests and test batteries available for cognitive assessment for adults and elderly.[ 24 , 25 ] Table 5 shows the list.

INVESTIGATIONS AND SIGNS OF POTENTIALLY REVERSIBLE DEMENTIAS

Once the suspicion for the cause for dementia (as a reversible dementia) is made based on the clinical features, confirmation of the cause is by the choice of correct investigation. Further, identification of the findings of the investigation that characterize those conditions is the next important step. Tables 6a - 6c show the investigations to be conducted/ordered for intracranial (neurosurgical), intracranial (neuroinfectious) and systemic (metabolic and endocrine) disorders. They also show the signs characteristic of the particular condition. While toxic conditions are confirmed by toxicology screens, no confirmatory tests are needed to diagnose mental and behavioural disorders; sleep apnoea however is diagnosed using the Apnoea index in polysomnography.

For autoimmune dementia and encephalopathy, cerebrospinal fluid analysis (CSF), testing for serum autoantibodies, neuroimaging (especially magnetic resonance imaging (MRI)) and complemented by EEG are suggested investigations. The CSF analysis shows inflammatory picture increased total white blood cell count, elevated protein >100 mg/dL, elevated oligoclonal bands or IgG index/synthesis rate.[ 9 ] Testing for serum autoantibodies can be done using commercially available kits. Elevated levels of autoantibodies are diagnostic of ADE. MRI has to be looked for mesial temporal signal abnormalities. EEG shows patterns specific to dementia/encephalopathy and may not be clinching.

Table 7 shows recommendations of various professional associations for investigations in cases of dementias. These primarily emphasize on identifying treatable dementias.

TREATMENT

Most important role of a psychiatrist is in delineating the clinical features, course and getting appropriate investigations. These steps are crucial in establishing the treatable causes of dementia. Once the cause is established or is indicative of, the next crucial step remains proper referral and liaison with appropriate super-speciality. Figure 2 shows treatment algorithm of various treatable causes of dementia for psychiatrists.

The two most important reversible/treatable causes that will be primarily managed by psychiatrists are depressive cognitive disorder and alcohol-related dementia (ARD).

Depressive Cognitive Disorder

Treatment of depressive cognitive disorder requires both pharmacological and psychotherapeutic approaches. The standard of care for treatment of depression, including the need for electroconvulsive therapy, must be followed for depressive cognitive disorder.[ 33 , 34 ] While treatment with antidepressants remains the mainstay of management, certain antidepressants have been found to be more effective for depression associated with cognitive difficulties. These include bupropion, duloxetine, fluoxetine, reboxetine, buspirone, tendospirone, vortioxetine and venlafaxine. Ketamine has also been suggested to be useful. Further, certain cognitive ameliorating agents have also been suggested. These include donepezil, memantine, modafinil and melatonin. Novel agents such as dehydroepiandrosterone and fludrocortisone (targeting neurosteroid dysregulation), erythropoietin, S-adenosylmethionine have also been suggested. Cognitive ameliorating agents and other newer agents are suggested to be used in combination with antidepressants.[ 35 ] Newer brain stimulation modalities, such as repetitive transcranial magnetic stimulation, are also suggested in cognitive impairment in depression.[ 36 ]

While there are sparse reports on risk of depressive cognitive disorder progressing into dementia, there are reports of late-life depression progressing to mild cognitive impairment (MCI) and dementia. Some reports of up to 70% risk.[ 37 ] Also, among cases with MCI, those with depressive symptoms tend to progress to dementia more.[ 37 ] In this context, there is a need to differentiate MCI with depression and depressive cognitive disorder. This differentiation is clinically made based on the antidepressant response to treatment. If cognitive impairments persist beyond improvement in depression symptoms, the possibility of a comorbid MCI is indicated. Neuroimaging-based differentiation may not be useful as hippocampal volume deficits are also seen in patients with depressive cognitive disorder.[ 38 ] However, distinct hippocampal functional network correlates have been shown in late-life depression and MCI.[ 39 ]

Delirium

Differentiating delirium from dementia is also an important aspect while discussing treatable dementias. We suggest the readers to refer to the clinical practice guidelines on management of delirium in elderly.[ 40 ]

Psychiatric disorders, in general and treatable/reversible cognitive impairment

A very recent registry based study from the United Kingdom suggests that severe psychiatric disorders, specifically schizophrenia, bipolar disorder, depression and mania and anxiety disorders, have an increased risk of developing dementia in later life.[ 41 ] Another very large cohort study showed that dementia patients have higher risk of psychiatric disorders both before and after dementia diagnosis.[ 42 ] Therefore, treatment of these disorders with an emphasis on recovery is very important in reducing the risk of later development of dementia.

Further, cognitive impairment across psychiatric disorders (as discussed in various clinical practice guidelines in this supplement issue)[ 43 , 44 , 45 ] is considered treatable and responds to the standard care of respective disorders. Further, adding cognitive training for cognitive impairment in these disorders has an important role.

Autoimmune dementia and encephalopathy

The treatment of paraneoplastic variety of ADE depends on the treatment of the cancers. Remission of cancer usually improves the symptoms of ADE. For non-paraneoplastic ADEs, acute treatment is use of corticosteroids, preferred intravenous (1 gram of intravenous methylprednisolone once daily for 3–5 days) or less preferred oral (prednisone (1 mg/kg/day)). The alternate treatment, when there are contraindications for use of steroids or occurrence of adverse effects to steroids, is the use of intravenous immunoglobulins (IVIG) (0.4 g/kg once daily for 3–5 days and then weekly for 6–12 weeks). Some studies have suggested the use of plasma exchange as well. Monitoring of side effects for these treatment lines has to be prompt and comprehensive.[ 9 ]

For patients showing relapses, maintenance treatment is recommended. Oral mycophenolate and azathioprine are the agents of choice in maintenance phase. Agents such as rituximab and cyclophosphamide are also suggested.[ 9 ]

Alcohol-related dementia

The treatment of ARD is two-staged. In the first stage, ARD has to be differentiated from WKS. If ARD is established with sufficient confidence, the mainstay of treatment has to focus on maintaining abstinence. Here, it is also important to understand that not all cases of ARD show complete reversibility; partial recovery is what is achieved and must be targeted. Evidence suggests that maintenance of abstinence is essential for reaching this target.[ 9 ] Perhaps, the standard of care, consisting of pharmacological management in terms of anti-craving agents and non-pharmacological management in the form of motivational enhancement therapy, relapse prevention therapy and other forms of cognitive behavioural therapy, must be followed.[ 46 , 47 ] Not only functional but also structural abnormalities tend to partially recover with abstinence.[ 9 ] Detailed management of cognitive impairment associated with alcohol is described in the respective clinical practice guidelines.[ 48 ]

Among the other treatable dementias that psychiatrists might consider offering treatments are- cognitive impairment related to B12 deficiency, obstructive sleep apnoea and thyroid dysfunctions.

Vitamin B12 deficiency

Unless there is a compelling reason not to like in palliative care situation or patient refusal, everyone with a proven vitamin B12 should receive treatment.

A few general principles apply to vitamin B12 mentioned below:

Urgency of correction : Most people with vitamin B12 exhibit no symptoms at all, developing symptoms gradually or as an accidental laboratory finding. In these cases, weekly supplementation of the vitamin can be implemented. But in circumstances like neuropsychiatric (NPS) abnormalities or neurological abnormalities, pregnancy and newborns, a more urgent correction and intensive monitoring are indicated. In rare cases of severe deficiency (and severe anaemia) and associated hemodynamic compromise blood transfusion may be an option.

Route of administration : Vit 12 are available for oral and parenteral route. VIT B12 IS NOT GIVEN INTRAVENOUSLY. Parenteral administration shall be provided to as said symptomatic individuals, those with NPS and those who do not have the capacity to absorb oral supplementation (e.g., pernicious anaemia [PA], intestinal blind loop). Oral route is preferred for those with nutritional deficiency, those with lack of access to parenteral administration facilities and/or patient preference. Moreso, high dose oral supplementation can be given in malabsorption states provided adherence is good, dose is sufficient, and a response is documented.

Available preparations : Two forms of Vit B12 are available, i.e., Cyanocobalamin, which has a cyanide (CN) group added during chemical manufacture, and hydroxocobalamin (also known as cobalamin). Both are effective in treatment of vitamin B12 deficiency and are available in India. Though, cyanocobalamin is predominantly used in the United States and hydroxocobalamin is predominantly used in Europe. Citing different kinetics, maintenance dosing frequency of cyanocobalamin is more frequent than hydroxocobalamin.

Duration of therapy : Duration depends upon the underlying aetiology of deficit. For those with a disease (such as autoantibodies to intrinsic factor [PA] or gastric bypass surgery) that cannot be reversed, lifetime replacement is required. Supplementation can be stopped once the deficiency is resolved if the underlying cause (such as an overly restrictive diet or a drug-induced deficiency) is removed.

Dose : Intramuscular (i.m) route is the most recommended route for Vit 12. Typical adult dose would be 1000 mcg intramuscularly once per week. But for NPS or anaemia, the recommended dose would be 1000 mcg intramuscularly alternate days for 1-2 weeks, and if aetiology is not reversible, then maintenance dose of 1000 mcg intramuscularly once a month (cyanocobalamin) lifelong or once every alternate month per month (hydroxocobalamin).

Oral dosing in adults with normal absorption is equally as effective as i.m dosing if given at a dose of 1000 mcg orally/day. But for individuals with impaired absorption, therapy with mega oral doses of oral vitamin B12 for, e.g., 2000-3000 mcg daily shall be effective.

Monitoring : More intensive monitoring may be required during supplementation for, e.g., every 2 to 3 days if given for concerning neurological or NPS. Whereas less frequent monitoring like once in 2 to 3 weeks may be required for conditions such as incidental deficiency. But additional testing (methylmalonic acid and homocysteine levels) may be required if there is lack of response. Once therapy is stopped, then it is prudent to monitor vitamin levels at least at 3 months.[ 49 ]

Folic acid deficiency

Oral folic acid (1-5 mg/day) is commonly used to treat folate insufficiency. This dosage is typically enough even in the presence of malabsorption because it is significantly higher than the 200 mcg (0.2 mg) suggested daily intake. For those with a reversible cause of deficiency (e.g., nutritional), folic acid is given for 1-4 months. For those with a chronic cause of folate deficiency, such as chronic haemolytic anaemia, therapy may be given indefinitely. Importantly, the neurologic manifestations of vitamin B12 deficiency will not be treated by folic acid. Thus, for NPS-like dementia, we need to investigate and supplement with both Vit B12 and folic acid.[ 49 ]

Routine administration of vitamin B12 or folic acid supplements without documented deficiency is not recommended.

Obstructive sleep apnoea

Use of continuous positive airway pressure for treatment of obstructive sleep apnoea has been shown to have significant positive impact on the cognitive functions too.[ 50 ] Here, strict patient compliance has to be assured. There is no role of cognitive enhancers in patients with obstructive sleep apnoea.

Hypothyroidism

Healthy adults who have been diagnosed with hypothyroidism for a few months should be started with levothyroxine dose of 1.6 mcg/kg/day and increase their dosage by 12.5 to 25 mcg/day every 6 to 8 weeks, depending on the condition. But those with cardiac disease or elderly over 65 years old initial starting dose shall be 25 mcg/day with a dose adjustment of 12.5 to 25 mcg every 4 to 6 weeks as needed. Patient shall be requested to use the same brand because of the narrow therapeutic index. Frequency of monitoring TSH levels shall be approximately 6 to 8 weeks after treatment initiating. Upon reaching the correct dosing of levothyroxine, frequency of monitoring shall reduce to 4 to 6 months and then every 12 months. It is important to note that in patients with age more than 65 yrs, there is also a physiological rise of TSH levels, so precaution shall be entertained in treating the subclinical phenotype of hypothyroidism.

Conditions such as normal pressure hydrocephalus do not require and do not respond specific pharmacological treatment for cognitive impairment.

Conflicts of interest

There are no conflicts of interest.

Acknowledgement

We thank Dr. Deepak Goel, Senior Consultant Neurologist, Max Hospital, Dehradun, and Dr. Asad Abbas, Senior Consultant Neurologist, Lucknow for their inputs on the content of the manuscript.

Funding Statement

Nil.

REFERENCES

1. Lee J, Meijer E, Langa KM, Ganguli M, Varghese M, Banerjee J, et al. Prevalence of dementia in India: National and state estimates from a nationwide study. Alzheimers Dement. 2023;19:2898–912. doi: 10.1002/alz.12928.

2. Ravindranath V, Sundarakumar JS. Changing demography and the challenge of dementia in India. Nat Rev Neurol. 2021;17:747–58. doi: 10.1038/s41582-021-00565-x.

3. Chari D, Ali R, Gupta R. Reversible dementia in elderly: Really uncommon? J Geriatr Ment Health. 2015;2:30–7.

4. Clarfield AM. The decreasing prevalence of reversible dementias: An updated meta-analysis. Arch Intern Med. 2003;163:2219–29. doi: 10.1001/archinte.163.18.2219.

5. Little MO. Reversible dementias. Clin Geriatr Med. 2018;34:537–62. doi: 10.1016/j.cger.2018.07.001.

6. Mahler ME, Cummings JL, Benson DF. Treatable dementias. West J Med. 1987;146:705–12.

7. Tripathi M, Vibha D. Reversible dementias. Indian J Psychiatry. 2009;51(Suppl 1(Suppl 1)):S52–5.

8. Piccini C, Bracco L, Amaducci L. Treatable and reversible dementias: An update. J Neurol Sci. 1998;153:172–81. doi: 10.1016/s0022-510x(97)00289-x.

9. Flanagan EP, Drubach DA, Boeve BF. Autoimmune dementia and encephalopathy. Handb Clin Neurol. 2016;133:247–67. doi: 10.1016/B978-0-444-63432-0.00014-1.

10. Ridley NJ, Draper B, Withall A. Alcohol-related dementia: An update of the evidence. Alzheimers Res Ther. 2013;5:3. doi: 10.1186/alzrt157.

11. Mouta S, Fonseca Vaz I, Pires M, Ramos S, Figueiredo D. What do we know about pseudodementia? Gen Psychiatr. 2023;36:e100939. doi: 10.1136/gpsych-2022-100939.

12. Bastiaansen AEM, van Steenhoven RW, de Bruijn MAAM, Crijnen YS, van Sonderen A, van Coevorden-Hameete MH, et al. Autoimmune encephalitis resembling dementia syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8:e1039. doi: 10.1212/NXI.0000000000001039. doi: 10.1212/NXI.0000000000001039.

13. Fernández-Fournier M, Lacruz L, Nozal P, Chico JL, Tallón Barranco A, Otero-Ortega L, et al. The study of neural antibodies in neurology: A practical summary. Front Immunol. 2022;13:1043723. doi: 10.3389/fimmu.2022.1043723.

14. Mishra KK, Sawant N, Garg S. Management of psychiatric disorders in patients with endocrine disorders. Indian J Psychiatry. 2022;64(Suppl 2):S402–13. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_30_22.

15. Munoli 2025 Clinical practice guidelines (CPG) on cognitive impairment associated with traumatic brain injury. Indian J Psychiatry. 2025;67:128–43. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_680_24.

16. The American Geriatrics Society 2015 Beers Criteria Update Expert Panel American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:2227–46. doi: 10.1111/jgs.13702.

17. O’Mahony D, O’Sullivan D, Byrne S, O’Connor MN, Ryan C, Gallagher P. STOPP/START criteria for potentially inappropriate prescribing in older people: Version 2. Age Ageing. 2015;44:213–8. doi: 10.1093/ageing/afu145.

18. Campbell NL, Perkins AJ, Bradt P, Perk S, Wielage RC, Boustani MA, et al. Association of anticholinergic burden with cognitive impairment and health care utilization among a diverse ambulatory older adult population. Pharmacotherapy. 2016;36:1123–31. doi: 10.1002/phar.1843.

19. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168:508–13. doi: 10.1001/archinternmed.2007.106.

20. UptoDate: Lexidrug. 2024. Available from: https://learn.wolterskluwercdi.com/search_lexi/?utm_source=google&utm_medium=search&utm_campaign=ind_lexicomp_brand_intl&utm_source=google&utm_medium=cpc&utm_campaign=IND_Lexicomp_Brand&utm_content=and utm_term=lexidrug&gad_source=1&gbraid=0AAAAAD_SI8eV6vEE-4dpY8npeb7-5vPCH&gclid=CjwKCAjw_Na1BhAlEiwAM-dm7JG16IswkWfFes0ZXqjB4ngr1Y5KOyxnoStU2jRF5YL8I0X4lMFUyRoCImwQAvD_BwE . [Last accessed on 2024 Jul 01]

21. Micromedex solutions. 2024. Available from: https://www.micromedexsolutions.com/home/dispatch . [Last accessed on 2024 Jul 01]

22. Epocrates. 2024. Available from: https://www.epocrates.com .[Last accessed on 2024 Jul 01]

23. WebMD. 2005–2024. Available from: https://www.webmd.com . [Last accessed on 2024 Jul 01]

24. Porrselvi AP, Shankar V. Status of cognitive testing of adults in India. Ann Indian Acad Neurol. 2017;20:334–40. doi: 10.4103/aian.AIAN_107_17.

25. Chakravarty K, Ray S. Cognitive screening tools for adults in Indian setting: A commentary. Ann Indian Acad Neurol. 2023;26:347–8. doi: 10.4103/aian.aian_394_23.

26. Pitner JK, Bachman DL. A synopsis of the practice parameters on dementia from the American Academy of neurology on the diagnosis of dementia. Consult Pharm. 2004;19:52–63. doi: 10.4140/tcp.n.2004.52.

27. Sorbi S, Hort J, Erkinjuntti T, Fladby T, Gainotti G, Gurvit H, et al. EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol. 2012;19:1159–79. doi: 10.1111/j.1468-1331.2012.03784.x.

28. The University of Sydney; 2016. Clinical Guidelines for Dementia. Available from: https://cdpc.sydney.edu.au/research/clinical-guidelines-for-dementia/ . [Last accessed on 2024 Jul 01]

29. Clinical Practice Guideline for Dementia 2017. Japanese Society of Neurology. 2017. Available from: https://www.neurology-jp.org/guidelinem/dementia/preface.html . [Last accessed on 2024 Jul 01]

30. Shaji KS, Sivakumar PT, Rao GP, Paul N. Clinical practice guidelines for management of dementia. Indian J Psychiatry. 2018;60(Suppl 3):S312–28. doi: 10.4103/0019-5545.224472.

31. Dementia: Assessment, management and support for people living with dementia and their carers. National Institute for Health and Care Excellence. 2018. Available from: https://www.nice.org.uk/guidance/ng97 . [Last accessed on 2024 Jul 01]

32. Ismail Z, Black SE, Camicioli R, Chertkow H, Herrmann N, Laforce R, Jr, et al. Recommendations of the 5th Canadian Consensus Conference on the diagnosis and treatment of dementia. Alzheimers Dement. 2020;16:1182–95. doi: 10.1002/alz.12105.

33. Gautam S, Jain A, Gautam M, Vahia VN, Grover S. Clinical practice guidelines for the management of depression. Indian J Psychiatry. 2017;59(Suppl 1):S34–50. doi: 10.4103/0019-5545.196973.

34. Avasthi A, Grover S. Clinical practice guidelines for management of depression in elderly. Indian J Psychiatry. 2018;60(Suppl 3):S341–62. doi: 10.4103/0019-5545.224474.

35. Colwell MJ, Tagomori H, Chapman S, Gillespie AL, Cowen PJ, Harmer CJ, et al. Pharmacological targeting of cognitive impairment in depression: Recent developments and challenges in human clinical research. Transl Psychiatry. 2022;12:484. doi: 10.1038/s41398-022-02249-6.

36. Tikka SK, Siddiqui MA, Garg S, Pattojoshi A, Gautam M. Clinical practice guidelines for the therapeutic use of repetitive transcranial magnetic stimulation in neuropsychiatric disorders. Indian J Psychiatry. 2023;65:270–88. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_492_22.

37. Mukku SSR, Dahale AB, Muniswamy NR, Muliyala KP, Sivakumar PT, Varghese M. Geriatric depression and cognitive impairment-An update. Indian J Psychol Med. 2021;43:286–93. doi: 10.1177/0253717620981556.

38. Sawyer K, Corsentino E, Sachs-Ericsson N, Steffens DC. Depression, hippocampal volume changes, and cognitive decline in a clinical sample of older depressed outpatients and non-depressed controls. Aging Ment Health. 2012;16:753–62. doi: 10.1080/13607863.2012.678478.

39. Xie C, Li W, Chen G, Ward BD, Franczak MB, Jones JL, et al. Late-life depression, mild cognitive impairment and hippocampal functional network architecture. Neuroimage Clin. 2013;3:311–20. doi: 10.1016/j.nicl.2013.09.002.

40. Grover S, Avasthi A. Clinical practice guidelines for management of delirium in elderly. Indian J Psychiatry. 2018;60(Suppl 3):S329–40. doi: 10.4103/0019-5545.224473.

41. Stevenson-Hoare J, Legge SE, Simmonds E, Han J, Owen MJ, O’Donovan M, et al. Severe psychiatric disorders are associated with increased risk of dementia. BMJ Ment Health. 2024;27:e301097. doi: 10.1136/bmjment-2024-301097.

42. Mo M, Zacarias-Pons L, Hoang MT, Mostafaei S, Jurado PG, Stark I, et al. Psychiatric disorders before and after dementia diagnosis. JAMA Netw Open. 2023;6:e2338080. doi: 10.1001/jamanetworkopen.2023.38080.

43. Grover 2025. Clinical practice guidelines (CPG) on cognitive impairment in schizophrenia. Indian J Psychiatry. 2025;67:65–83. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_690_24.

44. Muralidharan 2025. Clinical practice guidelines (CPG) on cognitive impairment in bipolar disorders. Indian J Psychiatry. 2025;67:84–97. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_696_24.

45. Priyaranjan Avinash. 2025. Clinical practice guidelines (CPG) on cognitive impairment in depression. Indian J Psychiatry. 2025;67:98–105. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_563_24.

46. Shen WW. Anticraving therapy for alcohol use disorder: A clinical review. Neuropsychopharmacol Rep. 2018;38:105–16. doi: 10.1002/npr2.12028.

47. Murthy P. Guidelines for psychosocial interventions in addictive disorders in India: An introduction and overview. Indian J Psychiatry. 2018;60(Suppl 4):S433–9. doi: 10.4103/psychiatry.IndianJPsychiatry_35_18.

48. Praharaj SK, Menon V, Ameen S. Clinical practice guidelines (CPG) on cognitive impairment in alcohol use disorders. Indian J Psychiatry. 2025;67:144–57. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_692_24.

49. Devalia V, Hamilton MS, Molloy AM; British Committee for Standards in Haematology Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166:496–513. doi: 10.1111/bjh.12959.

50. Krysta K, Bratek A, Zawada K, Stepańczak R. Cognitive deficits in adults with obstructive sleep apnea compared to children and adolescents. J Neural Transm (Vienna) 2017;124(Suppl 1):187–201. doi: 10.1007/s00702-015-1501-6.