Table 2.
Major findings of peer-reviewed papers assessing the effects of acute and chronic administration of pharmacological drugs on cortical reactivity in Alzheimer’s disease (AD), and assessing the predictive value of TMS measures for response to chronic administration of medication.
| PAPER | n | Age (yrs †) |
Gender (% M) |
Education (yrs†) |
Disease duration (mo †) |
Neurologic, Neuropsychiatric, and Neuropsychological Evaluation |
Pharmacol Challenge |
Effects on Cortical Reactivity | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diagnosis & Staging |
Anat scan |
NeuroΨ testing |
Meds | Muscle | MT (%) |
MEP (mV) |
CM CT |
SP (ms) |
SAI | ICI | ICF | |||||||
|
Acute administration of pharmacological drugs
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| #5 Liepert et al., 2001 | 10 | [n = 11: 74.8 ± 9.7] | [n = 11: 18.18] | - | - | [n = 11: CDR: 1.64 ± 0.64] | CT or MRI | MMSE WMT + other | No drugs affecting CNS | Donepezil 1 wk [5 mg/d] + 1 wk [10 mg/d] in 5 patients | Right FDI | - | - | - | N.S. | - | SIGN [SICI ⇑ after 10 mg] | N.S. |
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| #6 Di Lazzaro et al., 2002 | 6 | [n = 15: 69.0 ± 5.3] | [n = 15: 60.0] | [n = 15: 9.3 ± 3.4] | [n = 15: 28.4 ± 14.6] | NINCDS-ADRADA [Probable] | - | MMSE: 18.6 ± 3.5 RAVLT + Others | Naïve to AChEIs | Rivastigmine Single-dose [3 mg] | Left FDI | N.S. [RMT, AMT] | - | - | - | SIGN [⇑ in AD] N.S. [HC] | - | - |
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| 3 [HC] | 30.6 ± 2.3 | - | - | - | - | - | ||||||||||||
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| #9 Di Lazzaro et al., 2004 | 14 | [n = 28: 71.3 ± 6.8] | . | [n = 28: 8.2 ± 2.3] | [n = 28: 32.0 ± 16.8] | NINCDS-ADRADA [Probable] | - | MMSE: [n = 28: 19.35 ± 3.8] RAVLT + Others | Naïve to AchEIs/no other 30 days | Rivastigmine Single-dose [3 mg] | Left FDI | N.S. [RMT] | - | - | - | SIGN [⇑] | N.S. [SICI] | - |
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| #10 Pierantozzi et al., 2004 | 12 | 65.2 ± 3.5 | . | - | [Sympt not > 18 mo] | NINCDS-ADRADA [Possible] CDR: ≤ 1 | MRI | MMSE: 21.8 ± 2.1 NPB BDI / NPI | No AchEIs or other | Galantamine Single-dose [4 mg] | Right / Left APB | N.S. [RMT & AMT] | N.S. [MEP amp] | - | - | - | SIGN [⇑ SICI] | - |
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| #11 Di Lazzaro et al., 2005 | 14* [⇓ bas SAI] | [n = 20: 70.5 ± 6.9] | [n = 20: 40.0] | [n = 20: 7.9 ± 2.9] | [n = 20: 26.8 ± 16.4] | NINCDS-ADRADA [Possible] | - | MMSE: [n = 20: 19.1 ± 5.5] RAVLT + Others | Naïve to AchEIs/no other 30 days | Rivastigmine Single-dose [3 mg] | Left FDI | - | - | - | - | SIGN [⇑] | - | - |
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| #21 Martorana. et al., 2008 | 11 | 73.0 ± 9.2 | . | - | - | DSM-IV NINCDS-ADRADA CDR: ≥ 1.5 | MRI | MMSE: 15.74 ± 1.6 NPB/NPI UPDRS | No AChEIs or others | Melevodopa Single-dose [250 mg] + [Placebo in AD] | Right APB | N.S. [RMT & AMT in AD or HC] | - | - | - | - | SIGN [⇑SICI in AD] N.S. [HC] | N.S. [AD & HC] |
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| 12 [HC] | 68.0 ± 5.8 | . | - | - | - | - | . | - | ||||||||||
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| #23 Martorana et al., 2009 | 10 | 72.5 ± 6.1 | . | - | - | NINCDS-ADRADA [Probable] CDR: 1.75 ± 1.6 | MRI | MMSE: 18.23 ± 3.2 NPB | Naïve to AchEIs/no other 30 days | L-dopa Single-dose [125 mg] | Right FDI | N.S. [RMT in AD or HC] | N.S. [MEP amp in AD or HC] | - | - | SIGN [⇑ in AD] N.S. [HC] | - | - |
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| 10 [HC] | 71.7 ± 4.9 | . | - | - | - | - | - | - | ||||||||||
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Chronic administration of pharmacological drugs
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| #24 Pennisi et al., 2002 | 17 | [Range: 55-82] | 41.2 | - | - | NINCDS-ADRADA [Probable] | CT/MRI [diffuse atrophy in all; repeated at 1 yr] | MMSE: 11.76 ± 5.68 MMSE (1yr): 8.53 ± 5.14 | AChEIs 1 yr | Right / Left FDI | SIGN [⇓ R/L RMT] | N.S. | N.S. | - | - | - | - | |
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Predictors of response to chronic administration of pharmacological drugs
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| #11 Di Lazzaro et al., 2005 | 16** | [n = 20: 70.5 ± 6.9] | [n = 20: 40.0] | [n = 20: 7.9 ± 2.9] | [n = 20: 26.8 ± 16.4] | NINCDS-ADRADA [Possible] | - | MMSE [n = 20: 19.1 ± 5.5] RAVLT + Others | Rivastigmine 1 yr chronic tt | Left FDI | - | - | - | - | SIGN [⇑ in those w/⇓ bas SAI or ⇑ after s-d] | - | - | |
Legend. n: Number of subjects; yrs: Years; % M: Percentage of males; mo: Months; Anat scan: Anatomical scanning; NeuroΨ: Neuropsychologic; Meds: Medications; Pharmacol: Pharmacological; MT: Motor threshold; MEP: Motor evoked potential; mV: Microvolts; CMCT: Central motor conduction time; SP: Silent period; ms: Miliseconds; SAI: Short-latency afferent inhibition; ICI: Intracortical inhibition; ICF: Intracortical facilitation; CDR: Clinical Dementia Rating; CT: Computerized tomography; MRI: Magnetic resonance imaging; MMSE: Mini-Mental State Examination; WMT: Wechsler Memory Test; CNS: Central nervous system; wk: Week; mg/d: Miligram/day; FDI: First dorsal interosseus muscle; N.S.: Non-significant; SIGN: Significant; HC: Healthy control; NINCDS-ADRADA: National Institute of Neurological and Communicative Disorders and Stroke – Alzheimer’s Disease and Related Disorders Association; [Probable]: Probable AD; RAVLT: Rey Auditory Verbal Learning Test; AChEIs: Acetylcholinesterase Inhibitors; RMT: Resting motor threshold; AMT: Active motor threshold; SICI: Short-latency intracortical inhibition; Sympt: Symptoms; [Possible]: Possible AD; NPB: Neuropsychological battery; BDI: Beck Depression Inventory; NPI: Neuropsychiatry Inventory; APB: Abductor pollicis brevis muscle; amp: Amplitude; bas: baseline; DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th edition; UPDRS: Unified Parkinson Disease Rating Scale; R/L: Right/left; tt: Treatment; w/: With; s-d: Single-dose. Symbols. †: Mean ± standard deviation; %: Percent; >: more than; ≤: equal or less than; ≥: equal or more than; . : No data; –: Not done or not applicable; ⇑: Increased; *: 14 out of the initial 20 received single-dose of rivastigmine, specifically those who had low baseline SAI; ** 16 out of the initial 20 received rivastigmine for 1 year (treatment stopped in 4); ⇓: Decreased.