Rajesh R. Tampi, MD, MS, DFAPA

 (FTD) describes a group of neurodegenerative disorders that are characterized by the clinical syndrome of progressive dysfunction in executive functioning, behaviors, and language.

 FTD is thought to be the third most common type of dementia after Alzheimer disease (AD) and dementia with Lewy bodies.FTD is also a common type of early-onset dementia (occurring among individuals 65 years or younger).

FTD was noted in 1892 by Arnold Pick, MD, when he described an individual who presented with aphasia, temporal lobar atrophy, and presenile dementia.

 In 1911 the association between Pick bodies and FTD was described by Alois Alzheimer, MD, PhD, who named the disorder “Pick’s disease.” The term Pick’s disease became synonymous with FTD, referring to both the clinical syndrome and the pathological diagnosis. Currently, “Pick’s disease” is used only to describe the pathological diagnosis. In 1982, M. Marsel Mesulam, MD, identified the language subtype of FTD: primary progressive aphasia (PPA).

Available evidence indicates that FTD is the second most common cause of dementia among individuals 65 years or younger.

 The prevalence of FTD among individuals with early-onset dementia is between 3% and 26%. The population prevalence of FTD varies between 1 to 26 per 100,000.

 These numbers probably underestimate the true prevalence, as the disorder is often missed or misdiagnosed.

FTD has 2 main subtypes, based on their predominating presentations: the behavioral variant of FTD (bvFTD), and the language variant, ie, PPA.

 Based on the localizations and underlying cerebral dysfunction, the language variant can be further subdivided into the nonfluent variant of PPA (nfvPPA) and the semantic variant of PPA (svPPA). Male predominance has been noted in the bvFTD and svPPA variants and female predominance in the nfvPPA variant. 

 details the diagnostic criteria of FTD’s 3 variants.

A third variant of PPA has been described as logopenic PPA (lvPPA),in which individuals exhibit specific impairment with confrontation naming or word-finding difficulties and impaired sentence repetition.

 Neuroimaging studies among these individuals demonstrate predominant left posterior perisylvian or parietal atrophy/hypoperfusion/hypometabolism. Definite histopathologic evidence or the presence of a known pathogenic mutation allow for a definite diagnosis of FTD. 

Evidence indicates that approximately 12.5% of individuals with bvFTD have concomitant motor neuron disease.

 In addition, 27.3% of individuals have features of minor motor system dysfunction, including occasional fasciculations and mild muscle wasting or weakness. As the disease evolves, the clinical presentation of the 3 variants overlap with each other and with syndromes of atypical parkinsonism, including progressive supranuclear palsy (PSP) and corticobasal degeneration syndrome (CBS).

Compared with AD, patients with FTD tend to have a shorter duration of survival from diagnosis and more rapid decline of cognition and function.

 The average survival time with FTD depends on the subtype; the average survival time is approximately 3 years for bvFTD and motor neuron disease and 12 years for with svPPA.

Current evidence indicates that FTD is a highly heritable disorder, with familial FTD accounting for approximately one-third to half of cases.

 Most cases of familial FTD present as the bvFTD variant. A family history of dementia is found in 25% to 50% of FTD cases, and about 10% have a clear autosomal-dominant inheritance.

 Mutations in the microtubule-associated protein tau (τ), progranulin, and chromosome 9 open reading frame 72 expansion are the most common causes of familial FTD. These mutations result in the variable clinical presentations of FTD.

The major variants of FTD are classified based on their respective protein-based inclusions and underlying molecular pathologies.

 The current neuropathological classification allows most cases of FTD to be placed into 1 of 3 broad molecular subgroups: frontotemporal lobar degeneration (FTLD)-τ subtype; the FTLD-TDP subtype associated with TDP-43; or FET protein accumulation.

 The FTLD-τ variant accounts for approximately 40% of all FTD cases. Approximately half the postmortem cases of FTD have abnormal deposition of transactive response DNA-binding protein 43 (TDP-43).

FTD may be misdiagnosed as other psychiatric disorders, including schizophrenia, bipolar disorder, depression, or obsessive-compulsive disorder.

 The bvFTD variant is most likely to be misdiagnosed as another psychiatric disorder; FTD may be misdiagnosed as AD or another type of dementia. 

 describes the differentiating clinical features of the dementias.

Given the high risk for misdiagnosis, suspected cases of FTD should be carefully evaluated. A thorough history from the individual and a reliable collateral source that tracks the progression of behavioral and cognitive symptoms are essential. A focused physical examination that identifies parkinsonian and/or upper motor neuron signs will assist in the diagnosis. Laboratory testing (including complete metabolic panel, complete blood count, thyroid function tests, liver function tests, vitamin B12 levels, and urine drug screen) should be done to rule out reversible causes of cognitive and behavioral impairments. Among atypical cases, toxicology for heavy metals, inflammatory biomarkers for autoimmune and paraneoplastic syndromes, and testing for infectious etiologies including syphilis and HIV should be considered.

Neuroimaging studies including magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), and single photon emission computed tomography (SPECT) scans can also assist in diagnosing FTD. 

describes the neuroimaging findings in FTD.

 Cerebrospinal fluid (CSF) assessment will help rule out AD when the patient has low β-amyloid concentrations and high τ protein concentration. Neuropsychological testing will help rule out other causes of cognitive and functional changes. 

 provides neuropsychological profiles of various types of dementias.

 Among individuals with a family history of dementia, movement disorders, and/or psychotic disorders, genetic counseling and a search for genes that cause FTD are both recommended.

Currently there are no US Food and Drug Administration (FDA) approved disease-modifying drugs for the treatment of FTD.

 found a total of 9 randomized, controlled, double-blinded clinical trials that evaluated various drugs for the treatment of FTD.

 These included 2 trials of the selective serotonin reuptake inhibitor paroxetine, 1 trial of trazodone, 2 trials of stimulants (methylphenidate and dextroamphetamine), 1 trial of the acetylcholinesterase inhibitor galantamine, 2 trials of the N-methyl-d-aspartate (NMDA) antagonist memantine, and 1 trial of the neuropeptide oxytocin. The investigators concluded that SSRIs, trazodone, and the amphetamines may be effective in reducing some behavioral symptoms. None of these medications, however, improved cognition among individuals with FTD. Available data also indicated that these medications were well tolerated.

The evidence for the use of antipsychotics for the treatment of behavioral symptoms in FTD comes mainly from case reports and uncontrolled studies.

 In addition, the use of antipsychotics can worsen the risk of extrapyramidal adverse effects, to which individuals with FTD are especially vulnerable. Furthermore, the boxed warning for the risk for death with the use of antipsychotics among individuals with dementia holds true also for individuals with FTD. For the treatment of behavioral symptoms in FTD, the evidence for the use of anticonvulsants—including valproic acid, topiramate, and carbamazepine—is limited to case reports. Evidence indicates that individuals with FTD and parkinsonism often do not respond to dopaminergic drugs, including levodopa/carbidopa, although some case reports indicate some benefits with these agents. 

Trials of τ aggregation inhibitors, τ acetylation inhibitors, anti-τ active vaccine, anti-τ monoclonal antibodies, anti-human sortilin monoclonal antibody, microtubule-stabilizing drugs, and progranulin expression activators have been completed or are currently in various phases of trials.

 Unfortunately, available results indicate that none of these drugs have yet been found to be beneficial.

Available evidence indicates that nonpharmacological management techniques are helpful among individuals with FTD.

 These interventions include environmental approaches that assist individuals who struggle to accurately interpret, understand, and react to their environment. In addition, behavioral modification techniques and providing familiar activities appear to reduce different types of behaviors. Evidence indicates that educational services and coping strategies that are focused on problem-solving are effective in managing behavioral symptoms and reduce caregiver burden. The development of individualized regimens incorporating environmental and behavioral strategies have been proven to be highly beneficial in assisting individuals with FTD. The family caregivers who use these strategies become more competent in managing patients’ challenging behaviors. Speech therapy has been 

to be beneficial among individuals with PPA.

The clinical syndrome of FTD is characterized by executive dysfunction, behavioral disturbances, and language impairment. FTD is often misdiagnosed or underdiagnosed due to the heterogeneity of its clinical presentation and the overlap of its clinical symptoms with those of other common neuropsychiatric disorders. Although there are no FDA-approved medications for the treating FTD, some agents have shown modest efficacy in improving behavioral but not cognitive symptoms. Nonpharmacological techniques can be beneficial in managing behavioral symptoms. Many newer therapies are currently under trial, although their benefits are not yet certain.

is chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH; chief, Section for Geriatric Psychiatry, Cleveland Clinic, Cleveland, OH; and professor of medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH. 

is executive vice president, Diamond Healthcare, Richmond, VA. 

is with the Behavioral Advisory Group, Strongsville, OH. The authors report no conflicts of interest concerning the subject matter of this article.

1. Young JJ, Lavakumar M, Tampi D, Balachandran S, Tampi RR. 

Frontotemporal dementia: latest evidence and clinical implications

2. Bang J, Spina S, Miller BL. Frontotemporal dementia. 

3. Bott NT, Radke A, Stephens ML, Kramer JH. Frontotemporal dementia: diagnosis, deficits and management. 

4. Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioral variant of frontotemporal dementia. 

5. Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. 

6. Leyton CE, Hodges JR. Towards a clearer definition of logopenic progressive aphasia. 

7. Burrell JR, Kiernan MC, Vucic S, Hodges JR. Motor neuron dysfunction in frontotemporal dementia. 

8. Sivasathiaseelan H, Marshall CR, Agustus JL, et al. Frontotemporal dementia: a clinical review. 

9. Borroni B, Benussi A. Recent advances in understanding frontotemporal degeneration. F1000Res. 2019;8:F1000 Faculty Rev-2098.

10. Mackenzie IR, Neumann M. Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies. 

11. Darrow MD. A practical approach to dementia in the outpatient primary care setting. 

12. Gordon E, Rohrer JD, Fox NC. Advances in neuroimaging in frontotemporal dementia.

13. Burrell JR, Piguet O. Lifting the veil: how to use clinical neuropsychology to assess dementia. 

14. Liu M-N, Lau C-L, Lin C-P. Precision medicine for frontotemporal dementia. 

Pharmacological treatments for frontotemporal dementias: a systematic review of randomized controlled trials

16. Tsai RM, Boxer AL. Therapy and clinical trials in frontotemporal dementia: past, present, and future. 

17. Panza F, Lozupone M, Seripa D, et al. Development of disease-modifying drugs for frontotemporal dementia spectrum disorders. 

18. Barton C, Ketelle R, Merrilees J, Miller B. Non-pharmacological management of behavioral symptoms in frontotemporal and other dementias. 

Treatment of primary progressive aphasia.

Articles

Often misdiagnosed as other psychiatric disorders, FTD is the third most common type of dementia and the second most common among patients 65 years or younger. How to spot the signs.

Easy To Miss, Hard to Treat: Notes on Frontotemporal Dementia

The population of older adults with substance use disorders (SUDs) is increasing in the United States.

 It has been postulated that by the end of 2020 there will be approximately 5.7 million older adults with SUDs when compared with 2.8 million individuals in 20062;the number of emergency department visits for drug misuse on an average day for older patients can be seen in 

. Older adults tend to preferentially abuse alcohol, nicotine, and prescription medications while younger individuals use marijuana, cocaine, and heroin.

 There is a considerable scarcity of data regarding SUDs among older adults despite concerns of this issue being a major public health concern.

Older adults are considered an at-risk population for using psychoactive drugs, as aging is 

associated with an increased burden of health-related issues and psychosocial stressors that can increase the risks due to use of psychoactive drugs.

 It is estimated that at least 1 in 4 older adults has used psychoactive medications within a pattern of substance abuse.

 indicated that approximately 43% of individuals aged 65 years or older admitted to using alcohol in the past year with approximately 6.7% of these individuals reporting a pattern of alcohol abuse or dependence symptoms.

 The 2008-2009 US National Surveys on Drug Use and Health indicated that 14.1% of individuals aged 65 years or older reported past-year tobacco use when compared with 30.2% individuals aged 50 to 64 years.

2005 and 2006 National Surveys on Drug Use and Health

 found that among adults aged 65 years or older, 0.7% had used marijuana and 0.04% had used cocaine in the past year.

 The rates of past-year use of inhalants, hallucinogens, methamphetamine, and heroin were also low at less than 0.2%.

Among individuals aged 50 years or older, the past-year non-medical use of prescription opioids at 1.4% is more prevalent than the non-medical use of prescription sedatives (0.14%), tranquilizers (0.46%), and stimulants (0.16%).

 In this age group, the past-year prevalence of prescription opioid use disorders was low at 0.13%, but the risk of prescription opioid dependence was higher at 7.6%. Of concern is that in the US, 8.7% of individuals aged 65 to 80 years filled at least one prescription for benzodiazepines in a 1-year period with 31.4% of these individuals receiving benzodiazepines for longer than 120 days in a year.

 These data suggest a population at increased risk for SUDs and associated comorbidities.

Risk factors for the development of SUDs among older adults include a history of substance use, comorbid psychiatric disorders, and the presence of cognitive impairment.

 Factors that mitigate the development of SUDs include being married, no previous history of substance use, and a religious affiliation. SUDs are moderately to highly heritable; findings indicate that an individual’s risk would be proportional to the degree of genetic relationship to the relative with SUDs. For reference, the heritability rates for hallucinogen use disorder is 0.39 and for cocaine use disorder is 0.72.

SUDs among older adults is associated with worse medical outcomes and increased economic burden of care. The long-term use of psychoactive substances can result in adverse neurological outcomes even at therapeutic doses. These adverse effects include drowsiness, confusion, slowed psychomotor functioning, impaired reaction time, incoordination, ataxia, falls, and amnesia. The sustained use of psychoactive drugs often results in the development of physiological and physical dependence. Abrupt discontinuation of these drugs may result in serious withdrawal symptoms including delirium and seizures. The use of these substances may also result in problematic drug interactions with other prescribed medications or over-the-counter medical products.

Chronic use of psychoactive drugs can result in multiple medical complications including cardiac, hepatic, and renal impairments leading to greater rates of disability, morbidity and mortality. Approximately one-fifth of older adults who are hospitalized due to psychiatric disorders have a comorbid substance use disorder. 

 have higher rates of depression and suicide than age matched controls. The overall economic burden of substance use disorders among older adults is higher owing to greater risks for and rates of comorbidities, longer inpatient hospital stays and also the subsequent greater need for more intense outpatient programs to manage symptoms when compared with age matched controls.

Available evidence indicates that SUDs among older adults are often underdiagnosed and poorly treated.10 The reasons for this underdiagnosis and poor treatment include lack of awareness regarding these disorders, denial of the disorder, the shame and stigma of using addictive substances, reluctance to seek professional help, lack of financial resources, the lack of social supports, the presence of comorbid conditions, limited time spent with primary care physicians, and the ageist attitudes toward mental health disorders among older individuals.

The use of standard diagnostic criteria (eg, DSM-5), which are validated for use among younger adults tends to underestimate the prevalence of SUDs when among older adults. The 

Consensus Panel of the Treatment Improvement Protocol 

(TIP) recommends screening for alcohol and prescription drug use disorders as part of a regular physical examination among adults aged 60 years or older.11 The routine use of standardized screening instruments like the Michigan Alcohol Screening Test-Geriatric (MAST-G), the CAGE screening test, and computerized screening tools like the Drug and Alcohol Problem Assessment for Primary Care (DAPA-PC) can assist with the appropriate diagnosis of SUDs among older adults.

Available evidence indicates that treatments for SUDs among older adults are as successful as treatments for substance use disorders among younger adults.10 Programs that improve outcomes among older adults with SUDs include those that emphasize age-specific treatments, use of supportive and non-confrontational approaches that build self-esteem, emphasize cognitive-behavioral approaches, assist in development of skills to improve social support, use counselors who are trained and motivated to work with older adults and use of age-appropriate pace and content.

 Additionally, older adults have better outcomes when they are enrolled in programs where there is close monitoring for drug interactions and adverse effects of medication treatments.

 This is especially true among individuals withdrawing from alcohol and other drugs in which the withdrawal symptoms may be severe and prolonged.

are approved by the US Food and Drug Administration for the treatment of alcohol use disorder and buprenorphine is approved for the treatment of opiate use disorder among adults.

 However, the data on the use of these medications for the treatment of SUDs among older adults is limited. A review of the literature indicates that there are only two randomized controlled trials (RCTs) that evaluated the use of pharmacologic agents for SUDs among older adults. One trial evaluated the use of naltrexone when compared with placebo for the treatment of alcohol use disorder among individuals who were aged 50 to 70 years. The other trial evaluated the use of naltrexone or placebo as adjuncts with sertraline in the treatment of alcohol use disorder among individuals aged 55 years or older. Both trials showed that the use of naltrexone reduced the rates of relapse among older adults with alcohol use disorder. There are no RCTs that evaluated the use of buprenorphine, acamprosate, or disulfiram for SUDs among older adults. 

 illustrates the 5 steps that can ensure success in the treatment of substance use disorders among older adults.

The number of older adults with an SUD will increase appreciably in the near future. The currently available diagnostic criteria that have been developed to identify SUDs among younger individuals are less sensitive in identifying SUDs among older adults. The use of standardized screening tools and specific diagnostic criteria will improve the identification of older individuals with SUDs.

Older adults with SUDs respond well to treatments, if these programs are specifically designed to meet the needs of the older adult population. However, additional studies are needed because there is a dearth of evidence regarding pharmacotherapy for SUDs among older adults.

 is Chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH; Chief, Section for Geriatric Psychiatry, Cleveland Clinic, Cleveland, OH; and Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH.

 is Executive Vice President, Diamond Healthcare, Richmond, VA. 

Department of Psychiatry & Behavioral Sciences; and Medical Director, Alcohol & Drug Recovery Center, Cleveland Clinic Akron General, Akron, OH

The authors report no conflicts of interest concerning the subject matter of this article.

This article originally appeared online on July 9, 2020 under the title, "Substance Use Disorders Among Older Adults: Five Steps to Improve Outcomes," and has since been updated. -Ed.

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Addiction among older adults is associated with worse medical outcomes and increased economic burden of care. The long-term use of psychoactive substances can result in adverse neurological outcomes even at therapeutic doses. 

5 Steps to Improve Outcomes in Substance Abuse in Older Patients

Available data indicate that anxiety disorders are the most prevalent of psychiatric disorders among older adults.

 The National Comorbidity Survey Replication (NCS-R) found that among individuals aged 60 years or older, the prevalence of any anxiety disorder was 15.3% with specific phobia being the most prevalent: 7.5%; followed by social phobia: 6.6%; generalized anxiety disorder (GAD): 3.6%; PTSD: 2.5%; panic disorder: 2%; agoraphobia without panic: 1%; and OCD: 0.7% (

The risk factors for anxiety among older adults can be divided into external and internal factors. The external factors (ie, stress factors) include chronic medical illnesses, disability, and major illness in a spouse; internal factors (ie, vulnerability factors) include personality traits of neuroticism and low self-efficacy.

Among older adults, anxiety disorders are associated with reduced physical activity and functional status, poorer self-perceptions of health, decreased life satisfaction, increased loneliness, decreased quality of life, increased service use, and the overall greater cost of care. Anxiety disorders are also a 

Despite their prevalence, anxiety disorders among older adults are under-recognized and poorly treated. Among older adults, primary care physicians correctly made the diagnosis of any anxiety disorder in approximately 9% of the older adults.

 The most common reason for poor recognition the physical symptoms associated with anxiety disorders (eg, sleep disturbances, fatigue, restlessness, difficulty concentrating) tend to overlap with medical disorders commonly seen among older adults. Current diagnostic criteria for anxiety disorders were developed for use in younger individuals and are not sensitive to detecting these disorders in older adults, which further complicates recognition. And, these disorders often co-occur with depression, substance use disorders, and cognitive disorders among older adults, which makes the correct diagnosis more complex.

The initial step in evaluating older adults who present with symptoms of an anxiety disorder is to get a thorough history. Because anxiety disorders in older adults are highly comorbid with cognitive disorders, information from a collateral source is essential to clarify the history of symptoms. Eliciting history is often followed by a mental status examination and formal cognitive testing.

The next step is to assess for comorbid disorders (eg, depression, psychosis, cognitive dysfunction) and treat them. A focused physical examination and laboratory testing should also be completed to rule out co-occurring medical illness and adverse effects of prescribed drugs or drugs of abuse.

Although not specifically developed for use among older adults, standardized rating scales help with qualifying and quantifying the symptoms of anxiety. These rating scales can be divided into self-report scales and clinician-rated scales. The commonly available self-reported scales include the Worry Scale (WS), the State-Trait Anxiety Inventory (STAI), the Penn State Worry Questionnaire (PSWQ), Padua Inventory (PI), and the Beck Anxiety Inventory (BAI).

 Clinician-rated scales include the Structured Clinical Interview for DSM (SCID), the Diagnostic Interview Schedule (DIS), the Anxiety Disorders Interview Schedule (ADIS-R), and the Hamilton Anxiety Rating Scale (HARS). In cases in which anxiety disorders are comorbid with other psychiatric disorders including mood disorders, psychotic disorders, personality disorders, and/or 

, neuropsychological testing may be very useful in making the appropriate diagnoses and developing subsequent treatment plans.

Findings indicate that a stepped-care program reduces the 12-month and 24-month incidence of depressive and anxiety disorders by one-half of the usual care, and it is cost-effective.

 With this care model, older individuals sequentially receive a watchful waiting approach, cognitive behavioral therapy (CBT)-based bibliotherapy, cognitive behavioral therapy-based problem-solving treatment, and a referral to a primary care clinician for medication management as needed.

A meta-analysis of non-pharmacological interventions for late-life anxiety in 495 patients found that psychological interventions were more effective than no treatment on both self-rated and clinician-rated measures of anxiety with an effect size of 0.55.

 A meta-analysis that evaluated the efficacy of CBT alone, CBT with relaxation training, and relaxation training alone for late-life anxiety found that treatments were more effective than active control conditions.

 The researchers also found that CBT (alone or augmented with relaxation training) did not seem to add anything beyond relaxation training alone.

Data from 10 randomized controlled trials (RCTs) of antidepressants for late-life anxiety demonstrated that antidepressant use was associated with a significant reduction in anxiety symptoms at the end of the study period, but the trials predominantly included patients with generalized anxiety disorder (GAD) and there were limited data regarding the long-term use of antidepressants for anxiety.

In a soon to be published systematic review, Gupta and colleagues

 identified 5 RCTs that used benzodiazepines for treatment of anxiety disorders among older adults. They found that benzodiazepine use was associated with decreased anxiety at the end of each study period. Tolerability data showed mild adverse effects from the use of benzodiazepines. The main short comings of the study were limited data on the long-term use of benzodiazepines for anxiety and that the majority of the trials evaluated the use of benzodiazepines for GAD. Benzodiazepines should be used cautiously among older adults given their significant adverse effect profile including dependence, 

 sequenced treatment with pharmacotherapy and CBT for patients with GAD who were aged 60 or older. These individuals initially received 12 weeks of open-label escitalopram treatment. The researchers found that patients who received escitalopram augmented with CBT had improved response rates on the Penn State Worry Questionnaire compared with patients who received escitalopram alone. They also found that both escitalopram and CBT prevented relapse compared with placebo.

Anxiety disorders are not uncommon among older adults, but they are often underdiagnosed or misdiagnosed. And, they are associated with significant comorbidity and mortality among older patients. The development of specific diagnostic criteria that are applicable to older adults can aid in the accurate diagnosis of these disorders in late life. Psychotherapy that includes relaxation training and pharmacotherapy have been found efficacious for anxiety disorders among older adults.

 is Chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH; Chief, Section for Geriatric Psychiatry, Cleveland Clinic, Cleveland, OH; and Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH. 

 is Executive Vice President, Diamond Healthcare, Richmond, VA. The authors report no conflicts of interest concerning the subject matter of this article.

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2. Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. 

3. Becker E, Orellana Rios CL, Lahmann C, et al. 

Anxiety as a risk factor of Alzheimer’s disease and vascular dementia

4. Calleo J, Stanley MA, Greisinger A, et al. Generalized anxiety disorder in older medical patients: diagnostic recognition, mental health management and service utilization. 

5. Tampi RR, Tampi DJ. Anxiety disorders in late life: a comprehensive review. 

6. Nordhus IH, Pallesen S. Psychological treatment of late-life anxiety: an empirical review. 

7. Thorp SR, Ayers CR, Nuevo R, et al. Meta-analysis comparing different behavioral treatments for late-life anxiety. 

8. Balasubramaniam M, Joshi P, Alag P, et al. Antidepressants for anxiety disorders in late-life: a systematic review. 

9. Gupta A, Bhattacharya G, Farheen SA, et al. Systematic review of benzodiazepines for anxiety disorders in late life. 

10. Markota M, Rummans TA, Bostwick JM, Lapid MI. Benzodiazepine use in older adults: dangers, management, and alternative therapies. 

11. Wetherell JL, Petkus AJ, White KS, et al. 

Antidepressant medication augmented with cognitive-behavioral therapy for generalized anxiety disorder in older adults

The development of specific diagnostic criteria that are applicable to older adults can aid in the accurate diagnosis of psychiatric disorders in late life. 

The Most Prevalent Psychiatric Disorder in Older Adults

Rajesh R. Tampi, MD, MS, DFAPA, provides guidance for frontline health professionals and caregivers to mitigate stress and burden.

Dr Tampi is Chairman, Department of Psychiatry and Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH, and Chief, Section of Geriatric Psychiatry, and Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH

COVID-19: Quick Self-Check for Health Professionals

 neurodegenerative disorder in the US after Alzheimer disease (AD).

 It is estimated that in the US alone approximately 630,000 individuals have a diagnosis of PD. The prevalence of PD increases with age and it is estimated that the prevalence will double by 2040.

 The disorder is significantly more common among individuals aged 80 years or older compared with those aged 40 to 49 years (1903 per 100,000 population versus 41 per 100,000 population, respectively). The overall cost of caring for individuals with PD is approximately $52 billion per year.

Although not one of the cardinal features of PD, psychotic symptoms are seen in approximately 25% to 30% of individuals with PD.

 The risk factors for the development of psychotic symptoms in PD (ie, PD psychosis) include older age, greater severity of illness, longer duration of illness, the axial rigidity subtype of PD, idiopathic PD, underlying dementia, delirium or depression, the presence of sleep disturbance including REM behavior disorder, reduced vision, and the use of dopaminergic agents (

 PD psychosis is also associated with worsening quality of life, greater caregiver distress, higher rates of institutionalization, increased mortality, and greater health care costs.

Among individuals with PD, visual hallucinations are the most prevalent psychotic symptom (

 Visual hallucinations are seen in approximately one-quarter to one-third of individuals with PD, with a lifetime prevalence of about 50%.

 Auditory hallucinations occur in approximately 20% of individuals with PD. Certain minor phenomena such as the “sense of presence” and visual illusions can be seen among 17% to 72% of individuals with PD and these may progress to visual hallucinations as the illness progresses. Delusions are not very common with a prevalence of approximately 5%.

National Institute of Neurological Disorders and Stroke

 (NIMH) has proposed the following for the diagnosis of PD psychosis:

â¼ The presence of one or more of the following symptoms: illusions, false sense of presence, hallucinations, or delusion;

â¼ The UK brain bank criteria for the diagnosis of PD is met;

â¼ The symptoms occurred after the diagnosis of PD;

â¼ The symptoms are recurrent or continuous for 1 month;

â¼ The symptoms are not better accounted for by another cause of Parkinsonism (eg, dementia with Lewy bodies; psychiatric disorders such as schizophrenia, schizoaffective disorder; delusional disorder or mood disorder with psychotic features; a general medical condition including delirium);

â¼ PD psychosis could be associated with or without insight, with or without dementia, and with or without treatment for PD.

The exact pathophysiology of PD psychosis is unclear, but findings indicate that the cholecystokinin gene (CCK)-45C-T polymorphism is most often associated with PD psychosis.

 Moreover, alterations in the visual processing areas in the brain along with pathologies in the hippocampus and cholinergic brain structures are seen among individuals with PD psychosis. Frontal cognitive dysfunction, impaired visual processing, sleep-wake cycle dysregulation and brainstem dysfunction all contribute to the development of PD psychosis.

When assessing patients, a thorough history assists in identifying risk and precipitating factors for PD psychosis.

 Precipitating factors include medical conditions such as dehydration, infections, metabolic dysfunction; psychosocial factors include poor sleep and limited nutrition; psychological factors include stress and hospital admissions as well as the use of drugs like amantadine, anticholinergic drugs, dopaminergic drugs, and beta-blockers.

The Movement Disorder Society Task Force that evaluated the rating scales for assessing PD psychosis 

that none of the currently available scales adequately captured its entire phenomenology.

 They recommend that the following be used as primary scales in clinical trials evaluating new treatments for patients with PD psychosis: the Neuropsychiatric Inventory (NPI) for the cognitively impaired population or when a caregiver is required; Schedule for Assessment of Positive Symptoms (SAPS), Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) for the cognitively intact population or when the patient is the sole informant. The Clinical Global Impression Scale (CGIS) was suggested as a secondary outcome scale to measure change and response to treatment over time (See 

The first step in the management of PD psychosis is to assess the severity of symptoms. For mild symptoms that are not bothersome, there is no need for specific intervention other than providing reassurance and close monitoring to evaluate the progression of symptoms. The next step is to identify and treat for secondary causes of PD psychosis including medical disorders.

Medications that are used to treat the motor symptoms of PD may cause or worsen psychosis.

 A reduction or discontinuation of anticholinergics, monoamine oxidase inhibitors, levo- dopa, or dopamine agonists may result in the improvement of symptoms.

 If discontinuation of these agents is ineffective, psychotropic medications, may be indicated.

A systematic review of placebo-controlled trials by Wilby and colleagues

 demonstrated benefit for clozapine and pimavanserin for the treatment of PD psychosis. There were no definitive benefits noted for either quetiapine or olanzapine. The comparative studies showed improvements in PD psychosis symptoms when clozapine or comparator drug were assessed alone, but the data did not suggest any superiority of one active drug over the other drugs.

Pimavanserin, a novel 5-HT2A inverse agonist is the first FDA-approved antipsychotic for the treatment of hallucinations and delusions associated with PD psychosis.

 Pimavanserin improves symptoms of PD psychosis when compared with placebo (P = .0014). The adverse effect profile of pimavanserin include urinary tract infections, falls, peripheral edema, hallucinations, confusion, nausea, and headaches. Electroconvulsive therapy (ECT) has also been found to be beneficial for refractory symptoms.

Psychotic symptoms are not uncommon among patients with PD, and psychosis is associated with worse outcomes. Risk factors for PD psychosis include advancing age, more severe disease stage, cognitive impairments, depression, and sleep disorders.

The pathogenesis of PD psychosis involves neuropathological, neurochemical, and genetic changes. Management of PD psychosis involves treatment of underlying medical disorders and discontinuing drugs that may precipitate or worsen symptoms. Findings also indicate efficacy for clozapine and pimavanserin for the treatment of symptoms of PD psychosis. Pimavanserin remains the only FDA-approved medication for the treatment of PD psychosis. ECT may be beneficial for refractory PD psychosis symptoms.

 is Chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH, and Chief, Section of Geriatric Psychiatry, and Professor of Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH; 

1. Kowal SL, Dall TM, Chakrabarti R, et al. The current and projected economic burden of Parkinson disease in the United States. 

2. Pringsheim T, Jette N, Frolkis A, et al. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. 

3. Parkinson’s Foundation. Understanding Parkinsons: 

4. Ffytche DH, Creese B, Politis M, et al. The psychosis spectrum in Parkinson disease. 

5. Mack J, Rabins P, Anderson K, et al. Prevalence of psychotic symptoms in a community-based Parkinson disease sample. 

Parkinson disease psychosis is associated with worsening quality of life, greater caregiver distress, higher rates of institutionalization, increased mortality, and greater health care costs. The authors explore medical, psychosocial, and psychological factors associated with PD psychosis.

Rajesh R. Tampi, MD, MS, DFAPA

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