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Published Online: 24 April 2018

Methylphenidate Treatment for Patients With Posterior Cortical Atrophy

Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
Posterior cortical atrophy (PCA) is the progressive and disproportionate loss of visual functions associated with neurodegeneration of posterior cortical regions.1,2 Recent consensus criteria for PCA emphasize visuospatial and visuoperceptual deficits, relative sparing of memory and other cognitive functions, and posterior cortical abnormalities on neuroimaging.2 The most common cause of PCA is an early-onset visual variant of Alzheimer’s disease.3 Although there is no specific treatment for PCA or clear symptom response to Alzheimer’s medications, psychostimulants such as methylphenidate could potentially aid in improved shifting spatial attention and, hence, overall functioning among patients.4 Additionally, methylphenidate might improve the ability of patients with PCA to overcome lack of motivation and withdrawal consequential to visuospatial limitations. Here, case reports of three patients with PCA whose symptoms improved with methylphenidate treatment are presented.

Patient 1

A 56-year-old woman presented with 2 years of progressive visual localization difficulty, particularly affecting her ability to dress herself and to drive. On dressing, she could not pick out her clothes or put her arms through the sleeves. On driving, she could not stay in her lane, appropriately stop at stop signs, or park her car. Her Mini-Mental State Examination (MMSE) score was 21/30.5 She demonstrated normal language and memory but marked abnormalities on drawings and tasks involving overlapping or Gestalt figures, visual search, and letter location. Her neurological examination was otherwise normal. MRI results suggested that the patient had PCA, evident as parietal and posterior temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG-PET) (Figure 1A). CSF biomarkers for Alzheimer’s disease (β42 amyloid, total tau, and phosph-tau) confirmed a diagnosis of PCA due to Alzheimer’s,6 and the patient was treated with donepezil (10 mg/daily) and memantine extended release (28 mg/daily). She also received varying doses of escitalopram for mood and anxiety.
FIGURE 1. Fluorodeoxyglucose Positron Emission Tomography Images From Three Patients With Posterior Cortical Atrophy Due to Alzheimer’s Diseasea
a The images show posterior cortical hypometabolism concentrated in the parietal regions and adjacent temporal and occipital areas in A) patient 1, B) patient 2, and C) patient 3.
At the 2-year follow-up, the patient became poorly motivated beyond any depression or problems with mood. She had continued treatment with donepezil and memantine, without clear treatment response. However, her mood and anxiety had improved with escitalopram. She felt severely limited in activities of daily living due to the visuospatial deficits of Bálint’s syndrome (simultanagnosia, oculomotor apraxia, and optic ataxia), with an inability to even locate food and utensils placed before her. She was started on methylphenidate (5 mg twice/day) and become significantly more active. Although her visuospatial deficits and examination results did not improve, for the first time in several years she began spending significantly more time with her children, exercising, and socializing with friends.

Patient 2

A 57-year-old woman presented with 4 years of progressive visuospatial difficulties, such as localizing nobs and finding words on pages. She demonstrated an inability to use controls or a keyboard, to find a signature block on paperwork, and to read more than two lines on a page before the “words disappear.” Her MMSE score was 13/30. Her language was intact, but her memory was mild to moderately impaired. The main neurological deficits were observed on visuospatial tasks, including drawings and visual search localization. No further deficits were observed on other tasks. MRI results suggested a diagnosis of PCA, and temporoparietal and occipital hypometabolism was found on FDG-PET (Figure 1B). CSF biomarkers were consistent with Alzheimer’s, and the patient was treated with donepezil (10 mg/day), memantine (10 mg/twice daily), and escitalopram (10 mg/day) for depression with anxiety.
At the 2-year follow-up, the patient’s mood was generally euthymic, but she had become inactive and disengaged, primarily due to Bálint’s syndrome and visuospatial constraints. She had continued treatment with donepezil and memantine, without definite treatment response. However, she was euthymic, with minimal reported anxiety while receiving escitalopram. She was started on methylphenidate (5 mg/twice daily). Although neither her visuospatial deficits nor examination results improved, her family described her as initiating more activities, as well as walking more. Additionally, and to the surprise of her family, she was able to perform more than one task at a time.

Patient 3

A 62-year-old woman presented with 1 year of progressive visuospatial difficulties localizing keypad buttons on telephones and items on desks. She also showed environmental disorientation and was unable to drive. She described difficulty voting due to an inability to locate the circles on the punch ballot. On examination, the patient’s MMSE score was 27/30, her language was intact, and her memory was mildly impaired. However, she could not perform simple drawings, interpret overlapping or crosshatched figures, or localize dots or letters. Her neurological examination was otherwise normal. MRI results were nondiagnostic, but an FDG-PET showed parietal hypometabolism (Figure 1C). An amyloid PET scan was positive for amyloid neuritic plaques, consistent with PCA due to Alzheimer’s disease.6 Treatment included donepezil (10 mg/day) and memantine extended release (28 mg/day), as well as several antidepressants for both depression and anxiety.
At the 3-year follow-up, the patient had apathy out of proportion to any other evidence of depression or anxiety and consistent with pronounced and limiting visuospatial difficulties. She had continued treatment with donepezil and memantine with little treatment response. However, the addition of methylphenidate (5 mg b.i.d.) resulted in rapid improvement of her symptoms. She demonstrated increased engagement with her children, such as taking camping trips, and she had started participating in physical activities, such as exercise. Additionally, she had attended a college reunion.

Discussion

Among the three PCA patients above, treatment with low-dose methylphenidate was effective in attenuating some symptoms, without any reported adverse effects. Although their attention and visuospatial deficits were not improved, they became motivated and involved in activities. This observation is important, because there is no effective treatment for PCA, and patients with this disorder frequently withdraw and disengage because they are effectively visually impaired. The lack of motivation and initiation is often disproportionate to the effects on mood, and these symptoms may not respond to antidepressant medications.
Previous studies have reported that patients with Alzheimer’s disease who were treated with methylphenidate showed improved in symptoms.710 Apathy and poor motivation are common in Alzheimer’s disease, including PCA due to Alzheimer’s, and may result from dysfunction in the dopaminergic brain reward system, as well as from perceived inability to function in visual environments. Early research suggested that negative symptoms among patients with dementia, independent of depression, were responsive to methylphenidate treatment.11 Subsequent randomized, double-blind trials among outpatients with mild-to-moderate Alzheimer’s symptoms who were treated with methylphenidate (20 mg/day) and one open-label study reported improvements on apathy scores with treatment.710 Methylphenidate may be particularly helpful for patients with the PCA variant of Alzheimer’s, who often become poorly motivated to initiate activities due to limiting visuospatial impairments. Moreover, previous and current research suggest that methylphenidate may help to improve attention, depression, and decision-making behavior among patients with dementias.12
This preliminary report, along with previous work, highlights the need for research on the use of methylphenidate, or other psychostimulants, for the PCA variant of Alzheimer’s disease or other forms of visual impairment due to deficits in specific brain regions.

References

1.
Mendez MF, Ghajarania M, Perryman KM: Posterior cortical atrophy: clinical characteristics and differences compared to Alzheimer’s disease. Dement Geriatr Cogn Disord 2002; 14:33–40
2.
Crutch SJ, Schott JM, Rabinovici GD, et al: Alzheimer’s Association ISTAART Atypical Alzheimer’s Disease and Associated Syndromes Professional Interest Area: Consensus classification of posterior cortical atrophy. Alzheimers Dement 2017; 13:870–884
3.
Tang-Wai DF, Graff-Radford NR, Boeve BF, et al: Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy. Neurology 2004; 63:1168–1174
4.
Oken BS, Kishiyama SS, Kaye JA, et al: Attention deficit in Alzheimer’s disease is not simulated by an anticholinergic/antihistaminergic drug and is distinct from deficits in healthy aging. Neurology 1994; 44:657–662
5.
Folstein MF, Folstein SE, McHugh PR: “Mini-Mental State”: practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–198
6.
McKhann GM, Knopman DS, Chertkow H, et al: The diagnosis of dementia 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; 7:263–269
7.
Herrmann N, Rothenburg LS, Black SE, et al: Methylphenidate for the treatment of apathy in Alzheimer disease: prediction of response using dextroamphetamine challenge. J Clin Psychopharmacol 2008; 28:296–301
8.
Lanctot KL, Chau SA, Herrmann N, et al: Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial. Int Psychogeriatr 2014; 26(2):239–246
9.
Rosenberg PB, Lanctôt KL, Drye LT, et al: ADMET Investigators: Safety and efficacy of methylphenidate for apathy in Alzheimer’s disease: a randomized, placebo-controlled trial. J Clin Psychiatry 2013; 74:810–816
10.
Padala PR, Burke WJ, Shostrom VK, et al: Methylphenidate for apathy and functional status in dementia of the Alzheimer type. Am J Geriatr Psychiatry 2010; 18:371–374
11.
Galynker I, Ieronimo C, Miner C, et al: Methylphenidate treatment of negative symptoms in patients with dementia. J Neuropsychiatry Clin Neurosci 1997; 9:231–239
12.
Rahman S, Robbins TW, Hodges JR, et al: Methylphenidate (‘Ritalin’) can ameliorate abnormal risk-taking behavior in the frontal variant of frontotemporal dementia. Neuropsychopharmacology 2006; 31:651–658

Information & Authors

Information

Published In

Go to The Journal of Neuropsychiatry and Clinical Neurosciences
Go to The Journal of Neuropsychiatry and Clinical Neurosciences
The Journal of Neuropsychiatry and Clinical Neurosciences
Pages: 334 - 336
PubMed: 29685063

History

Received: 19 December 2017
Revision received: 21 January 2018
Accepted: 14 February 2018
Published online: 24 April 2018
Published in print: Fall 2018

Keywords

  1. Alzheimer-s Disease
  2. Cerebral Disorders
  3. CNS Stimulants
  4. Dementia

Authors

Details

Mario F. Mendez, M.D., Ph.D. [email protected]
From the Departments of Neurology and Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California at Los Angeles; and the Neurobehavior Unit, V.A. Greater Los Angeles Healthcare System.

Notes

Send correspondence to Dr. Mendez; e-mail: [email protected]

Funding Information

NIA: 1RF1AG050967-01
Supported by the U.S. National Institute on Aging (grant 1RF1AG050967-01).The author reports no financial relationships with commercial interests.

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